Author: "Jean Philippe Haymann" / Publisher: hal ccsd - Searchworks@Jio Institute Digital Library Search Results

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1. Detection and localization of calcium oxalate in kidney using synchrotron deep ultraviolet fluorescence microscopy

Author: Emmanuel Estève, David Buob, Frédéric Jamme, Chantal Jouanneau, Slavka Kascakova, Jean-Philippe Haymann, Emmanuel Letavernier, Louise Galmiche, Pierre Ronco, Michel Daudon, Dominique Bazin, Matthieu Réfrégiers, Common and Rare Kidney Diseases = Maladies Rénales Fréquentes et Rares: des Mécanismes Moléculaires à la Médecine Personnalisée (CORAKID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Département de Néphrologie [CHU Tenon] (Néphrologie et dialyse), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pathologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Departement Hospitalo-Universitaire Hepatinov [Hôpital Paul Brousse - APHP], Hôpital Paul Brousse, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Chimie Physique (ICP), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée (CoRaKID), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Refregiers, Matthieu
Subjects: oxalosis, Nuclear and High Energy Physics, 030232 urology & nephrology, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, macromolecular substances, Kidney, kidney biopsies, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, synchrotron diagnosis, 03 medical and health sciences, 0302 clinical medicine, deep ultraviolet microscopy, Humans, Instrumentation, 030304 developmental biology, 0303 health sciences, oxalate, Radiation, Calcium Oxalate, urogenital system, equipment and supplies, Research Papers, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Microscopy, Fluorescence, Case-Control Studies, biological sciences, Synchrotrons
Abstract: Synchrotron deep ultraviolet imaging highlighting pathological calcium oxalate detection in kidney is presented., Renal oxalosis is a rare cause of renal failure whose diagnosis can be challenging. Synchrotron deep ultraviolet (UV) fluorescence was assayed to improve oxalosis detection on kidney biopsies spatial resolution and sensitivity compared with the Fourier transform infrared microspectroscopy gold standard. The fluorescence spectrum of synthetic mono-, di- and tri-hydrated calcium oxalate was investigated using a microspectrometer coupled to the synchrotron UV beamline DISCO, Synchrotron SOLEIL, France. The obtained spectra were used to detect oxalocalcic crystals in a case control study of 42 human kidney biopsies including 19 renal oxalosis due to primary (PHO, n = 11) and secondary hyperoxaluria (SHO, n = 8), seven samples from PHO patients who received combined kidney and liver transplants, and 16 controls. For all oxalocalcic hydrates samples, a fluorescence signal is detected at 420 nm. These spectra were used to identify standard oxalocalcic crystals in patients with PHO or SHO. They also revealed micrometric crystallites as well as non-aggregated oxalate accumulation in tubular cells. A nine-points histological score was established for the diagnosis of renal oxalosis with 100% specificity (76–100) and a 73% sensitivity (43–90). Oxalate tubular accumulation and higher histological score were correlated to lower estimated glomerular filtration rate and higher urinary oxalate over creatinine ratio.
Published: 2022

2. Atypical clinical presentation of Autosomal Recessive Polycystic Kidney Mimicking Medullary Sponge Kidney disease

Author: Emmanuel Letavernier, Madeline Schwoehrer, Marine Livrozet, Camille Saint-Jacques, Laure Raymond, Radoslava Saraeva, Jean-Philippe Haymann, Vincent Frochot, Michel Daudon, Laurent Mesnard, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Common and Rare Kidney Diseases = Maladies Rénales Fréquentes et Rares: des Mécanismes Moléculaires à la Médecine Personnalisée (CORAKID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Eurofins Biomnis, Service des soins intensifs néphrologiques et rein aigu [CHU Tenon] (SINRA ), Institut des Sciences du Calcul et des Données (ISCD), and Sorbonne Université (SU)
Subjects: 0303 health sciences, 03 medical and health sciences, 0302 clinical medicine, Nephrology, 030232 urology & nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 3. Good health
Abstract: International audience
Published: 2021

3. Primary Hyperparathyroidism in Homozygous Sickle Cell Patients: A Hemolysis-Mediated Hypocalciuric Hypercalcemia Phenotype?

Author: Edmat Akhtar Khan, Rosa Vargas-Poussou, Remi Chieze, Lynda Cheddani, Jean-Philippe Haymann, Vincent Frochot, Emmanuel Letavernier, Camille Saint-Jacques, V. Avellino, François Lionnet, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], HAL-SU, Gestionnaire, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Calcitriol, endocrine system diseases, chemistry.chemical_element, familial hypocalciuric hypercalcemia, Calcium, Asymptomatic, Gastroenterology, Article, 03 medical and health sciences, 0302 clinical medicine, FeCa2+, Internal medicine, hemic and lymphatic diseases, medicine, Hypercalciuria, 030212 general & internal medicine, primary hyperparathyroidism, 030304 developmental biology, Calcium metabolism, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Familial hypocalciuric hypercalcemia, business.industry, General Medicine, medicine.disease, Urinary calcium, 3. Good health, chemistry, Medicine, sickle cell disease, medicine.symptom, hemolysis, business, Primary hyperparathyroidism, urinary calcium, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Primary hyperparathyroidism (pHPT) has been reported to have a higher prevalence in sickle cell disease (SCD) patients, including a high rate of recurrence following surgery. However, most patients are asymptomatic at the time of diagnosis, with surprisingly infrequent hypercalciuria, raising the issue of renal calcium handling in SCD patients. We conducted a retrospective study including (1) 64 hypercalcemic pHPT non-SCD patients, (2) 177 SCD patients, divided into two groups of 12 hypercalcemic pHPT and 165 non-pHPT, (3) eight patients with a diagnosis of familial hypocalciuric hypercalcemia (FHH). Demographic and biological parameters at the time of diagnosis were collected and compared between the different groups. Determinants of fasting fractional excretion of calcium (FeCa2+) were also analyzed in non-pHPT SCD patients. Compared to non-SCD pHPT patients, our data show a similar ionized calcium and PTH concentration, with a lower plasmatic calcitriol concentration and a lower daily urinary calcium excretion in pHPT SCD patients (p &lt, 0.0001 in both cases). Fasting FeCa2+ is also surprisingly low in pHPT SCD patients, and thus inadequate to be considered hypercalcemia, recalling the FHH phenotype. FeCa2+ is also low in the non-pHPT SCD control group, and negatively associated with PTH and hemolytic biomarkers such as LDH and low hemoglobin. Our data suggest that the pHPT biochemical phenotype in SCD patients resembles the FHH phenotype, and the fasting FeCa2+ association with chronic hemolysis biomarkers strengthens the view of a potential pharmacological link between hemolytic by-products and calcium reabsorption, potentially through a decreased calcium-sensing receptor (CaSR) activity.
Published: 2021

4. Amoxicillin crystalluria is associated with acute kidney injury in patients treated for acute infective endocarditis

Author: Julien Ternacle, Nicolas Mongardon, Sovannarith San, Michel Daudon, Jean-Philippe Haymann, Emmanuel Letavernier, Pascal Lim, Antonio Fiore, Amina Moussafeur, Raphaël Lepeule, Leopold Oliver, Matthieu Jamme, Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), CHU Henri Mondor, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Urgences néphrologiques et transplantation rénale [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Nephrolithiasis, Amoxicillin, Anti-Bacterial Agents, Humans, Acute Kidney Injury, Endocarditis, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Crystalluria, Acute infective endocarditis, In patient, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Transplantation, business.industry, Acute kidney injury, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Nephrology, medicine.symptom, business, medicine.drug
Abstract: International audience
Published: 2021

5. La cystinurie et ses traitements : une approche physiopathologique

Author: Michel Daudon, Dominique Bazin, Marine Livrozet, Jean-Philippe Haymann, Emmanuel Letavernier, Vincent Frochot, Steeve Doizi, Julie Rode, Olivier Traxer, Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: 03 medical and health sciences, 0302 clinical medicine, Urology, 030232 urology & nephrology, 030204 cardiovascular system & hematology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Resume La cystinurie est une maladie monogenique induisant une perte de fonction d’un transporteur d’acides amines dibasiques implique dans la reabsorption de cystine au niveau des tubules renaux proximaux. L’excretion urinaire de cystine chez ces patients est augmentee d’un rapport 10 a 60 par rapport au sujet sain, responsable d’une sursaturation avec precipitation de cristaux de cystine dans les reins et de calculs dans les cavites excretrices. La physiopathologie de la cystinurie est particuliere : la concentration plasmatique de cystine est souvent normale alors que l’absorption intestinale est diminuee. Ce paradoxe est explique par une absorption intestinale preservee de cysteine et de methionine qui sont deux acides amines soufres metabolises notamment en cystine. Le principe du traitement consiste a empecher la formation de cristaux de cystine dans les reins afin de prevenir la survenue d’une maladie lithiasique, mais aussi d’une authentique nephropathie cristalline responsable d’une insuffisance renale chez plus de la moitie des patients. Le traitement medical des patients cystinuriques repose (1) sur une diminution de l’excretion urinaire quotidienne de cystine qui est le reflet de l’absorption intestinale et donc des apports en methionine ; (2) sur une augmentation du seuil de solubilite urinaire de la cystine afin de prevenir une precipitation cristalline intratubulaire et intracavitaire par une dilution et une alcalinisation des urines avec des valeurs cibles de 3 L et un pH urinaire aux alentour de 7,5. Le traitement par sulfhydryle dont le but est de dissocier les ponts disulfures des molecules de cystine avec un effet modeste sur la dissolution des calculs de cystine constitues ne devrait en toute logique etre utilise en dernier recours une fois les mesures dietetiques et la cible de pH urinaire obtenue.
Published: 2021

6. Advances in the identification of calcium carbonate urinary crystals

Author: Michel Daudon, Emmanuel Letavernier, Ivan T. Lucas, Giovanni B. Fogazzi, Dominique Bazin, Vincent Frochot, Vincent Castiglione, Jean Philippe Haymann, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Liège (CHU-Liège), Laboratoire Interfaces et Systèmes Electrochimiques (LISE), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Physique (ICP), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratorio Clinico e di Ricerca sul Sedimento Urinario, Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico [Milan, Italy], Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Martin, Véronique, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Materials science, Spectrophotometry, Infrared, Clinical Biochemistry, Energy-dispersive X-ray spectroscopy, Analytical chemistry, Infrared spectroscopy, engineering.material, Spectrum Analysis, Raman, Biochemistry, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Calcium Carbonate, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, 0302 clinical medicine, Vaterite, [CHIM] Chemical Sciences, Humans, [CHIM]Chemical Sciences, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Spectroscopy, Infrared microspectroscopy, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Urinary sediment, Calcite, Aragonite, Biochemistry (medical), General Medicine, Middle Aged, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Energy dispersive X-Ray spectroscopy, 030104 developmental biology, Calcium carbonate, chemistry, 030220 oncology & carcinogenesis, Raman spectroscopy, Microscopy, Electron, Scanning, engineering, symbols, Calcium carbonate crystals
Abstract: International audience; The examination of the urinary sediment of a 64-year-old woman showed the presence of three different types of crystals, all with unusual morphology, which could not be identified with bright field microscopy, polarized light, and the knowledge of urine pH (7.5). The use of microscopic infrared spectroscopy, Raman spectroscopy and energy dispersive X-ray spectroscopy led to the identification of the three types of crystals as calcite, vaterite and aragonite, which are all variants of calcium carbonate crystals. This paper confirms the complex morphology and nature that urinary crystals may at times have and the utility of advanced infrared spectroscopy techniques for their identification.
Published: 2021

7. Inflammation plays a critical role in 2,8-dihydroxyadenine nephropathy

Author: Dominique Bazin, Vincent Frochot, Michel Daudon, Felix Renaudin, Sophie Vandermeersch, Amélie E. Coudert, Hang-Korng Ea, Jean-Philippe Haymann, Emmanuel Letavernier, Ellie Tang, Camille Saint-Jacques, Elise Bouderlique, Joëlle Perez, Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: 0303 health sciences, business.industry, 030232 urology & nephrology, Inflammation, Building and Construction, medicine.disease, Nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Immunology, medicine, Electrical and Electronic Engineering, medicine.symptom, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030304 developmental biology, 2,8-Dihydroxyadenine
Abstract: International audience
Published: 2021

8. Medullary sponge kidney: what kind of stones?

Author: Vincent Frochot, Michel Daudon, Jean-Philippe Haymann, Emmanuel Letavernier, Dominique Bazin, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Chimie-Physique (LCP), Université de Cocody, Bazin, Dominique, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: [CHIM.ANAL] Chemical Sciences/Analytical chemistry, business.industry, 030232 urology & nephrology, Building and Construction, Anatomy, Medullary sponge kidney, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, 030212 general & internal medicine, Electrical and Electronic Engineering, business, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2021

9. Whitlockite structures in kidney stones indicate infectious origin: a scanning electron microscopy and Synchrotron Radiation investigation

Author: Bénédicte Ménez, Elise Bouderlique, Jean-Philippe Haymann, Emmanuel Letavernier, Erik Elkaim, Dominique Bazin, Nathaniel S. Hwang, Vincent Frochot, Michel Daudon, Frederik Tielens, Marine Livrozet, Louis Hennet, Robert J. Papoular, Raphaël Weil, Dominique Thiaudière, Céline Pisapia, Institut de Chimie Physique (ICP), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire Léon Brillouin (LLB - UMR 12), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, LLB - Nouvelles frontières dans les matériaux quantiques (NFMQ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Solides (LPS), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPGP), Institut national des sciences de l'Univers (INSU - CNRS)-IPG PARIS-Université de La Réunion (UR)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Seoul National University [Seoul] (SNU), Vrije Universiteit Brussel (VUB), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Interfaces, Confinement, Matériaux et Nanostructures ( ICMN), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPGP (UMR_7154)), Institut national des sciences de l'Univers (INSU - CNRS)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hennet, Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chemistry, and General Chemistry
Subjects: Chemistry(all), diagnosis, Whitlockite, 030232 urology & nephrology, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, engineering.material, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, Kidney stone, Electrical and Electronic Engineering, 030304 developmental biology, 0303 health sciences, Chemistry, Building and Construction, X-ray scattering, Molecular biology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, infection, 3. Good health, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, SEM, Chemical Engineering(all), engineering, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract: International audience; Dans cette contribution, nous étudions les calculs rénaux contenant la whitlockite (Wk). En premier lieu, la présence du fer dans la formule stœchiométrique de la Wk est discutée grâce à la fluorescence X. Puis, nous abordons la relation à l’infection à l’aide d’observations au Microscope électronique à balayage (MEB) aptes à mettre en évidence de possibles empreintes de bactéries. Elles montrent que le processus infectieux est établi pour des teneurs supérieures à 20%, ceux-ci ne pouvant toutefois pas être écartés en dessous de cette teneur. Finalement, l’étude de relation entre la taille des cristaux de Wk et l’infection par DRX ne permet pas de l’établir. Le message pour le clinicien est le suivant : pour un patient asymptomatique, si le calcul ne contient ni struvite, ni apatite carbonatée et moins de 20% de Wk, il convient d’observer par MEB les calculs rénaux afin de pouvoir écarter ou non un processus infectieux.
Published: 2021

10. Crystal size in μ crystalline pathologies and its clinical implication

Author: Jean-Philippe Haymann, Emmanuel Letavernier, Vincent Frochot, Dominique Bazin, Michel Daudon, Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: Materials science, 030232 urology & nephrology, 02 engineering and technology, Building and Construction, 021001 nanoscience & nanotechnology, Crystal, 03 medical and health sciences, Crystallography, 0302 clinical medicine, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Electrical and Electronic Engineering, 0210 nano-technology, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2021

11. Prevalence of metabolic abnormalities in patients with urolithiasis in Kinshasa, the Democratic Republic of Congo

Author: Ernest Kiswaya Sumaili, Pablo Kuntima Diasiama Diangienda, Alain Ngoma Mayindu, Jean-Philippe Haymann, Dieudonné Molamba Moningo, Augustin M. L. Punga-Maole, Michel Daudon, Service d’Urologie [Kinshasa, Congo], Cliniques Universitaires de Kinshasa [Congo], Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, MESH: Hydrogen-Ion Concentration, hypocitraturia, Urine, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, MESH: Urinary Calculi, MESH: Urine, chemistry.chemical_compound, 0302 clinical medicine, Urolithiasis, Risk Factors, MESH: Risk Factors, Prevalence, Medicine, 030212 general & internal medicine, education.field_of_study, MESH: Middle Aged, MESH: Diuresis, General Medicine, Hydrogen-Ion Concentration, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, MESH: Young Adult, Democratic Republic of the Congo, Female, Urinary Calculi, Hypocitraturia, Adult, medicine.medical_specialty, MESH: Citric Acid, insufficient diuresis, composition, Urinary system, 030231 tropical medicine, Population, Diuresis, engineering.material, Citric Acid, Young Adult, 03 medical and health sciences, MESH: Urolithiasis, MESH: Cross-Sectional Studies, Internal medicine, Humans, education, MESH: Prevalence, Creatinine, MESH: Humans, business.industry, Research, Whewellite, MESH: Adult, MESH: Democratic Republic of the Congo, MESH: Male, Cross-Sectional Studies, chemistry, engineering, Uric acid, business, MESH: Female
Abstract: International audience; Introduction: metabolic abnormalities are key factors in urolithiasis patients because they can be modified to prevent the risk of urinary stones. The objectives of this study were to estimate the frequency of metabolic abnormalities in the urine of patients with urolithiasis and to determine their possible link with the chemical composition of stones.Methods: we conducted a cross-sectional study evaluating 73 patients referred for urolithiasis in 8 clinics in Kinshasa, between January 2017 and September 2019. Twenty four-hour or early morning urine were collected and analyzed in the Tenon Hospital in Paris. Parameters analyzed included pH, specific gravity, creatinine, uric acid, calcium, phosphate, oxalate, citrate and magnesium. Chi square test or chi-square likelihood-ratio and student's t test were used as statistical tests.Results: overall, 89% (n=65) of patients with lithiasis had metabolic abnormalities. Mean (SD) age of patients was 47.0 (14.2) years with male to female ratio of 1.6: 1. The mean (SD) 24-hour diuresis was 1836.4 (1216.9) ml; the mean (SD) urine density was 1.018 (0.007); and the mean (SD) pH was 6.1(0.8). Hypocitraturia was the most frequently observed metabolic abnormality and was found in 76.7% patients. Other significant metabolic abnormalities were low magnesuria (35.6%), hyperoxaluria (11%), and low sulphaturia (74%). Whewellite (73.5%) was the main chemical component. The mean pH was higher in patients with carbapatite and struvite stones (p=0.031).Conclusion: this study suggests that inadequate diuresis and hypocitraturia were important lithogenic factors. The population should be encouraged to increase water intake to limit the frequency of urine super saturation with crystals.
Published: 2021

12. The crucial contribution of X-ray fluorescence spectroscopy in medicine

Author: Eddy Foy, Cristian Mocuta, Dominique Bazin, Jean-Philippe Haymann, Michel Daudon, Barbara Fayard, Hester Colboc, Solenn Reguer, Stéphan Rouzière, Laboratoire de Chimie Physique D'Orsay (LCPO), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie-Physique (LCP), Université de Cocody, Institut de Chimie Physique (ICP), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Solides (LPS), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), IRAMAT - Laboratoire Métallurgies et Cultures (IRAMAT-LMC), Institut de Recherche sur les Archéomatériaux (IRAMAT), Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université d'Orléans (UO)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Laboratoire Archéomatériaux et Prévision de l'Altération (LAPA - UMR 3685), Nanosciences et Innovation pour les Matériaux, la Biomédecine et l'Energie (ex SIS2M) (NIMBE UMR 3685), Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Rayonnement Matière de Saclay (IRAMIS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Synchrotron Radiation for Biomedicine = Rayonnement SynchroTROn pour la Recherche BiomédicalE (STROBE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], UMR S702 Remodelage et Réparation du Tissu Rénal, Institut National de la Santé et de la Recherche Médicale (INSERM), ANR-09-BLAN-0120,NANOSHAP,Hydroxyapatites substituées nanocristallisées et leurs interfaces avec les milieux biologiques(2009), ANR-12-BS08-0022,CAPYROSIS,Formation de cristaux de pyrophosphates de calcium et arthrose : études in vitro et in vivo(2012), and ANR-13-JSV1-0010,DRAPO,Identification des déterminants de la Plaque de Randall et de l'épidémie de lithiase urinaire: une approche multidisciplinaire.(2013)
Subjects: 0303 health sciences, Materials science, [SDV]Life Sciences [q-bio], 010401 analytical chemistry, Analytical chemistry, Building and Construction, 01 natural sciences, X-Ray Fluorescence Spectroscopy, 0104 chemical sciences, 03 medical and health sciences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, [CHIM]Chemical Sciences, Electrical and Electronic Engineering, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience; This contribution tries to indicate to the clinician what kind of information can be investigated through X-ray fluorescence, what kind of information can be extracted from this spectroscopy and finally how it competes with other tools described in previous publications such as Fourier Transform Infrared or Raman spectroscopy, X-ray Absorption Near Edge Structure spectroscopy and X-ray diffraction. To attain this goal, several examples based on X-ray fluorescence experiments performed on biological samples namely concretions, medical devices, biological fluids as well as tissues are presented.
Published: 2021

13. Less arterial stiffness in kidney transplant recipients than chronic kidney disease patients matched for renal function

Author: Tilman B. Drüeke, Marie Essig, Lynda Cheddani, Ziad A. Massy, Jean Philippe Haymann, Jean-Jacques Boffa, Michel Delahousse, Emmanuel Letavernier, Sophie Liabeuf, Nahid Tabibzadeh, Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service Néphrologie/Dialyse [AP-HP Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Foch [Suresnes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], and Gestionnaire, Hal Sorbonne Université
Subjects: cardiovascular risk, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal function, kidney transplantation, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, AcademicSubjects/MED00340, Pulse wave velocity, Kidney transplantation, 2. Zero hunger, Transplantation, business.industry, Odds ratio, Original Articles, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], carotid-femoral pulse wave velocity (CF-PWV), Nephrology, Arterial stiffness, Cardiology, business, Body mass index, chronic kidney disease, Kidney disease
Abstract: Background Chronic kidney disease is associated with a high cardiovascular risk. Compared with glomerular filtration rate–matched CKD patients (CKDps), we previously reported a 2.7-fold greater risk of global mortality among kidney transplant recipients (KTRs). We then examined aortic stiffness [evaluated by carotid–femoral pulse wave velocity (CF-PWV)] and cardiovascular risk in KTRs compared with CKDps with comparable measured glomerular filtration rate (mGFR). Methods We analysed CF-PWV in two cohorts: TransplanTest (KTRs) and NephroTest (CKDps). Propensity scores were calculated including six variables: mGFR, age, sex, mean blood pressure (MBP), body mass index (BMI) and heart rate. After propensity score matching, we included 137 KTRs and 226 CKDps. Descriptive data were completed by logistic regression for CF-PWV values higher than the median (>10.6 m/s). Results At 12 months post-transplant, KTRs had significantly lower CF-PWV than CKDps (10.1 versus 11.0 m/s, P = 0.008) despite no difference at 3 months post-transplant (10.5 versus 11.0 m/s, P = 0.242). A lower occurrence of high arterial stiffness was noted among KTRs compared with CKDps (38.0% versus 57.1%, P Conclusions Aortic stiffness was significantly less marked in KTRs 1 year post-transplant than in CKDps matched for GFR and other variables. This observation is compatible with the view that the pathogenesis of post-transplant cardiovascular disease differs, at least in part, from that of CKD per se.
Published: 2020

14. 24-h Urine Collection: A Relevant Tool in CKD Nutrition Evaluation

Author: Moustafa Abdel-Nabey, Camille Saint-Jacques, Jean-Jacques Boffa, Vincent Frochot, Marine Livrozet, Michel Daudon, Martin Flamant, Emmanuel Letavernier, Jean-Philippe Haymann, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, 24 h-urine collection, [SDV]Life Sciences [q-bio], Reproducibility of Results, lcsh:TX341-641, Middle Aged, Nutrition Surveys, Article, Diet, Cohort Studies, diet protein intake, nutrition, Humans, Patient Compliance, salt, Female, Renal Insufficiency, Chronic, lcsh:Nutrition. Foods and food supply, chronic kidney disease, Follow-Up Studies, Urine Specimen Collection
Abstract: Dietary management is a cornerstone of Chronic Kidney Disease (CKD) monitoring, and dietary surveys often difficult to perform. We studied in a CKD patient cohort with two years follow-up, whether validated 24-h urine ionogram would be a relevant tool for diet evaluation and compliance. We included 404 non-dialysis CKD patients, with three evaluations, including repeated measurements of fractional renal creatinine clearance and 24-h urine collection. Completeness of the 24-h urine collection, assessed by daily urine creatinine excretion extrapolated from fractional creatinine clearance, was 64.6%, 75.5%, and 78.2% at the first, second, and third visits, respectively. One hundred sixty-eight patients (41.6%) had three complete collections, with a measured glomerular filtration of 42.3 mL/min/1.73 m2 at baseline and prevalence of anemia and secondary hyperparathyroidism of 13.9% and 26.2%, respectively, increasing during follow-up to 15% and 31.5% (p &lt, 0.001 and p &lt, 0.001). The urine analysis showed at baseline a urine volume of above 2 L/day, and estimated sodium and protein intake within targets in 51.6% and 40.3% of cases, which improved during follow-up only for protein (to 45.9%, p &lt, 0.0001). Our data suggest that a 24-h urine ionogram is an interesting, reliable tool in CKD patients for dietary monitoring to achieve target recommendation noteworthy salt and protein intake.
Published: 2020

15. The Case | Fluctuating serum creatinine and crystals in urine

Author: Marine Livrozet, Michel Daudon, Dominique Bazin, Vincent Frochot, Jeremy Zaworski, Jean-François Benoist, Jean-Jacques Boffa, Jean-Philippe Haymann, Emmanuel Letavernier, Emmanuel Esteve, Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: 0303 health sciences, Creatinine, medicine.medical_specialty, business.industry, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Urology, Urine, Body Fluids, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, chemistry, Nephrology, Heterocyclic Compounds, medicine, [CHIM]Chemical Sciences, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2020

16. The Case | Pseudorenal failure with metabolic acidosis in a 34-year-old woman

Author: Marie Joncquel-Chevalier Curt, Victor Fages, Arnaud Lionet, Joseph Vamecq, Jean-Philippe Haymann, Common and Rare Kidney Diseases = Maladies Rénales Fréquentes et Rares: des Mécanismes Moléculaires à la Médecine Personnalisée (CORAKID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Maladies RAres du DEveloppement embryonnaire et du MEtabolisme : du Phénotype au Génotype et à la Fonction - ULR 7364 (RADEME), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), and Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée (CoRaKID)
Subjects: Adult, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Recommended Dietary Allowances, Gastroenterology, Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Text mining, Internal medicine, medicine, Humans, Endoscopy, Digestive System, Renal Insufficiency, Dyspepsia, 030304 developmental biology, 0303 health sciences, business.industry, Metabolic acidosis, Creatine, medicine.disease, Renal Elimination, Nephrology, Creatinine, 030220 oncology & carcinogenesis, Dietary Supplements, Female, Antacids, Creatinine blood, Acidosis, business, Creatinine metabolism
Published: 2019

17. Resistance to Insulin in Patients with Gitelman Syndrome and a Subtle Intermediate Phenotype in Heterozygous Carriers: A Cross-Sectional Study

Author: Rosa Vargas-Poussou, Renaud de la Faille, Jean-Philippe Haymann, Olivier Devuyst, Ivan Tack, Pascal Houillier, Damien Bergerot, Armelle Arnoux, Julien Allard, Marguerite Hureaux, Anne Blanchard, Michel Azizi, Stéphanie Baron, Xavier Jeunemaitre, Aurelie Dinut, Pierre-Yves Courand, Marion Vallet, Pierre-Hadrien Becker, Laurence Dubourg, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Zurich, Vargas-Poussou, Rosa, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, and UCL - (SLuc) Service de néphrologie
Subjects: medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 610 Medicine & health, Type 2 diabetes, 030204 cardiovascular system & hematology, 10052 Institute of Physiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Tubulopathy, Internal medicine, Vitamin D and neurology, medicine, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, Aldosterone, 2727 Nephrology, business.industry, Insulin, General Medicine, Gitelman syndrome, medicine.disease, 3. Good health, Endocrinology, chemistry, Nephrology, 570 Life sciences, biology, business, Body mass index
Abstract: Background Gitelman syndrome is a salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive sodium-chloride cotransporter. Previous studies suggested an intermediate phenotype for heterozygous carriers. Methods To evaluate the phenotype of heterozygous carriers of pathogenic SLC12A3 mutations, we performed a cross-sectional study of patients with Gitelman syndrome, heterozygous carriers, and healthy noncarriers. Participants measured their BP at home for three consecutive days before hospital admission for blood and urine sampling and an oral glucose tolerance test. Results We enrolled 242 participants, aged 18-75 years, including 81 heterozygous carriers, 82 healthy noncarriers, and 79 patients with Gitelman syndrome. The three groups had similar age, sex ratio, and body mass index. Compared with healthy noncarriers, heterozygous carriers showed significantly higher serum calcium concentration (P=0.01) and a trend for higher plasma aldosterone (P=0.06), but measures of home BP, plasma and urine electrolytes, renin, parathyroid hormone, vitamin D, and response to oral glucose tolerance testing were similar. Patients with Gitelman syndrome had lower systolic BP and higher heart rate than noncarriers and heterozygote carriers; they also had significantly higher fasting serum glucose concentration, higher levels of markers of insulin resistance, and a three-fold higher sensitivity to overweight. According to oral glucose tolerance testing, approximately 14% of patients with Gitelman syndrome were prediabetic, compared with 5% of heterozygous carriers and 4% of healthy noncarriers. Conclusions Heterozygous carriers had a weak intermediate phenotype, between that of healthy noncarriers and patients with Gitelman syndrome. Moreover, the latter are at risk for development of type 2 diabetes, indicating the heightened importance of body weight control in these patients.
Published: 2019

18. Fasting Urinary Osmolality, CKD Progression, and Mortality: A Prospective Observational Study

Author: Jean-Philippe Haymann, Emmanuel Letavernier, Emmanuelle Vidal-Petiot, Martin Flamant, H. Fessi, Christian Jacquot, Jean-Jacques Boffa, Caroline du Halgouet, Pascal Houillier, Marion Vallet, Sandra Wagner, Gérard Maruani, Renaud de la Faille, François Vrtovsnik, Pierre Ronco, Eric Thervet, Eric Daugas, Marine Livrozet, Laurence Nicolet-Barousse, Marie Metzger, Bénédicte Stengel, Nahid Tabibzadeh, Alexandre Karras, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), French-Clinical Research Infrastructure Network [Lyon] (FCRIN INI-CRCT - Coordination Nationale Réseau FORCE), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunopathologie rénale, récepteurs et inflammation, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, CHU Tenon [APHP], Service de Néphrologie et Dialyses [CHU Tenon], Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Néphrologie et Hémodialyse [CHU HEGP], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, F-CRIN, INICRCT network, Paris, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), and NephroTest Study Group: Marine Livrozet, Emmanuel Letavernier, Pierre Ronco, Hafedh Fessi, Emmanuelle Vidal-Petiot, Eric Daugas, Caroline du Halgouet, Renaud de La Faille, Gerard Maruani, Marion Vallet, Laurence Nicolet-Barousse, Alexandre Karras, Christian Jacquot
Subjects: Male, urine concentration ability, 030232 urology & nephrology, Urine osmolality, urologic and male genital diseases, tubular damage, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, Prospective Studies, prognostic factor, ComputingMilieux_MISCELLANEOUS, Fasting, Middle Aged, Prognosis, female genital diseases and pregnancy complications, 3. Good health, Survival Rate, Nephrology, Disease Progression, Biomarker (medicine), biomarker, Female, France, medicine.symptom, glomerular filtration rate (GFR), Cohort study, Glomerular Filtration Rate, medicine.medical_specialty, Urinary system, CKD progression, Urology, chronic kidney disease (CKD), 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Risk factor, Renal Insufficiency, Chronic, business.industry, Osmolar Concentration, medicine.disease, measured GFR (mGFR), Decreased glomerular filtration rate, end-stage renal disease (ESRD), Albuminuria, GFR decline, business, Biomarkers, Kidney disease
Abstract: International audience; Rationale & objective: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD).Study design: Prospective longitudinal cohort study.Setting & participants: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study.Predictor: Fasting urinary osmolality measured using delta cryoscopy.Outcomes: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51Cr-EDTA renal clearance.Analytical approach: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR.Results: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H2O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile.Limitations: Fasting was self-reported.Conclusions: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression.
Published: 2019

19. Stiripentol protects against calcium oxalate nephrolithiasis and ethylene glycol poisoning

Author: Marine Le Dudal, Jean-Philippe Haymann, Vincent Frochot, Rima Nabbout, Elise Bouderlique, Emmanuel Letavernier, Sophie Vandermeersch, Georges Deschênes, Joëlle Perez, Laurent Baud, Michel Daudon, Carole Martori, Léa Huguet, Ellie Tang, Nicole Chemaly, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Ecole nationale Veterinaire d'Alfort (ENVA) (EpiMAI USC Epi), École nationale vétérinaire d'Alfort (ENVA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and AP-HP Hôpital universitaire Robert-Debré [Paris]
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Calcium oxalate, Epilepsies, Myoclonic, urologic and male genital diseases, Kidney, Nephrolithiasis, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Oxalate, Nephropathy, Rats, Sprague-Dawley, Excretion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dravet syndrome, Oral administration, Internal medicine, Stiripentol, medicine, Animals, Humans, Ethylene glycol, Calcium Oxalate, Dioxolanes, General Medicine, medicine.disease, Rats, 3. Good health, 030104 developmental biology, Endocrinology, chemistry, Ethylene glycol poisoning, 030220 oncology & carcinogenesis, Hyperoxaluria, Primary, Hepatocytes, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, Primary hyperoxaluria, medicine.drug
Abstract: International audience; Increased urinary oxalate excretion (hyperoxaluria) promotes the formation of calcium oxalate crystals. Monogenic diseases due to hepatic enzyme deficiency result in chronic hyperoxaluria, promoting end-stage renal disease in children and young adults. Ethylene glycol poisoning also results in hyperoxaluria, promoting acute renal failure and frequently death. Stiripentol is an antiepileptic drug used to treat children affected by Dravet syndrome. It has been shown to inhibit neuronal lactate dehydrogenase 5 enzyme. As this isoenzyme is also the last step of hepatic oxalate production, we hypothesized that stiripentol would potentially reduce hepatic oxalate production and urine oxalate excretion. In vitro, stiripentol decreased the synthesis of oxalate by hepatocytes in a dose-dependent manner. In vivo, oral administration of stiripentol significantly reduced urine oxalate excretion in rats. Stiripentol protected the kidneys against calcium oxalate crystal deposits in acute ethylene glycol intoxication and chronic calcium oxalate nephropathy models. In both models, stiripentol significantly improved renal function. Patients affected by Dravet syndrome and treated with stiripentol had a lower urine oxalate excretion than control patients. A young girl affected by severe type I hyperoxaluria received stiripentol for several weeks, and urine oxalate excretion decreased by two-thirds. Stiripentol is a promising potential therapy against genetic hyperoxaluria and ethylene glycol poisoning.
Published: 2019

20. Daily Green Tea Infusions in Hypercalciuric Renal Stone Patients: No Evidence for Increased Stone Risk Factors or Oxalate-Dependent Stones

Author: Yahia Benzerara, Dominique Bazin, Michel Daudon, Olivier Traxer, Jean-Philippe Haymann, Emmanuel Letavernier, Andras Hoznek, Arnaud Dessombz, Mohamed Tligui, Nahid Tabibzadeh, Julie Rode, Gestionnaire, Hal Sorbonne Université, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'urologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'Urologie [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'urologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, 030232 urology & nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Medicine, Hypercalciuria, Stone composition, Food science, hypercalciuria, Aged, 80 and over, Oxalates, education.field_of_study, oxalate, Nutrition and Dietetics, food and beverages, Hydrogen-Ion Concentration, Middle Aged, 3. Good health, 030220 oncology & carcinogenesis, Female, lcsh:Nutrition. Foods and food supply, Adult, Adolescent, green tea, Population, education, chemistry.chemical_element, lcsh:TX341-641, Urinalysis, Calcium, complex mixtures, Article, Citric Acid, Oxalate, Kidney Calculi, Young Adult, 03 medical and health sciences, mental disorders, Humans, Aged, Renal stone, Tea, business.industry, renal stone, Green tea, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Diet, Uric Acid, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Cross-Sectional Studies, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, calcium oxalate monohydrate, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science, CALCIUM OXALATE MONOHYDRATE
Abstract: Green tea is widely used as a &lsquo, &rsquo, healthy&rsquo, beverage due to its high level of antioxidant polyphenol compounds. However tea is also known to contain significant amount of oxalate. The objective was to determine, in a cross-sectional observational study among a population of 273 hypercalciuric stone-formers referred to our center for metabolic evaluation, whether daily green tea drinkers (n = 41) experienced increased stone risk factors (especially for oxalate) compared to non-drinkers. Stone risk factors and stone composition were analyzed according to green tea status and sex. In 24-h urine collection, the comparison between green tea drinkers and non-drinkers showed no difference for stone risk factors such as urine oxalate, calcium, urate, citrate, and pH. In females, the prevalence of calcium oxalate dihydrate (COD) and calcium phosphate stones, assessed by infrared analysis (IRS) was similar between green tea drinkers and non-drinkers, whereas prevalence of calcium oxalate monohydrate (COM) stones was strikingly decreased in green tea drinkers (0% vs. 42%, p = 0.04), with data in accordance with a decreased oxalate supersaturation index. In males, stone composition and supersaturation indexes were similar between the two groups. Our data show no evidence for increased stone risk factors or oxalate-dependent stones in daily green tea drinkers.
Published: 2019

21. Urothelium proliferation is a trigger for renal crystal deposits in a murine lithogenesis model

Author: Vincent Frochot, Léa Huguet, Sophie Vandermeersch, Sandrine Placier, Héloïse Bilbault, Joëlle Perez, Nahid Tabibzadeh, Jean-Philippe Haymann, Emmanuel Letavernier, Michel Daudon, Dominique Bazin, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Grouped Recherche Clinique lithiase, Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), and Fondation pour la Recherche Médicale (n° DEA20140630461)
Subjects: 0301 basic medicine, FGF7 Administration, medicine.medical_specialty, Fibroblast Growth Factor 7, Urothelial Cell, Normal diet, Science, 030232 urology & nephrology, Urothelial cell proliferation, Calcium oxalate, chemistry.chemical_element, Calcium, Crystal Deposition, Kidney, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Article, Kidney Calculi, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Animals, Osteopontin, Urothelium, Cell Proliferation, Multidisciplinary, biology, Urothelial Cell Proliferation, FGF7 Groups, medicine.disease, Crystal Retention, Mice, Inbred C57BL, Disease Models, Animal, Phenotype, 030104 developmental biology, Endocrinology, chemistry, biology.protein, Medicine, Female, Nephrocalcinosis
Abstract: Most mouse kidney stone models induce nephrocalcinosis rather than urolithiasis. The aim of our study was to find an accelerated experimental model in order to study the early events of stone formation, that is, at the time of crystal binding to intrarenal urothelium. C57B6 mice exposed to vitamin D supplements and water containing hydroxyl-L-proline, ammonium chloride and calcium chloride were studied for 42 days. A group receiving urothelial cell mitogen Fibroblast Growth Factor 7 (FGF7) was compared to control group receiving saline. Calcium oxalate monohydrate (COM) crystals were detected in urines by day 2 and within urinary spaces in specialized fornix areas in both groups as soon as day 14 with enhanced deposits in FGF7 group compared to controls at day 21. Urothelial cells proliferation, uroplakin III downregulation and de novo expression of osteopontin receptor CD44 detected in FGF7 group, were delayed in the control group (day 42). Crystal aggregates within specialized fornix areas by day 42 were located in urinary spaces but also within and under a multilayered metaplastic urothelium, simultaneous to macrophages influx. Point of note, administration of a normal diet by day 21 was responsible for a spontaneous crystal clearance. Our data show that under supersaturation conditions, urothelial cell proliferation and calcium oxalate crystal retention occur within specialized fornix areas. Enhanced crystal deposits following FGF7 administration suggest that urothelium proliferation would be a relevant trigger for renal stone formation.
Published: 2018

22. ABCC6 Deficiency Promotes Development of Randall Plaque

Author: Gilles Kauffenstein, Elise Bouderlique, Nastassia Navasiolava, Léa Delaitre, Viola Pomozi, Ludovic Martin, Joëlle Perez, Jean-Philippe Haymann, Emmanuel Letavernier, Olivier Le Saux, Marie-Christine Verpont, Léa Huguet, Michel Daudon, Ellie Tang, Janna Zoll, Marta de Frutos, Georges Leftheriotis, Dominique Bazin, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), University of Hawai'i [Honolulu] (UH), Laboratoire de PhysioMédecine Moléculaire (LP2M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and HAL-SU, Gestionnaire
Subjects: Male, 0301 basic medicine, Pathology, 030232 urology & nephrology, Urine, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cohort Studies, Mice, 0302 clinical medicine, Pseudoxanthoma Elasticum, Kidney, biology, Incidence, Biopsy, Needle, Calcinosis, Soft tissue, genetic renal disease, General Medicine, Prognosis, Pseudoxanthoma elasticum, Immunohistochemistry, 3. Good health, mineral metabolism, medicine.anatomical_structure, Nephrology, Female, Multidrug Resistance-Associated Proteins, medicine.medical_specialty, ABCC6, Urinalysis, Risk Assessment, Kidney Calculi, 03 medical and health sciences, medicine, Animals, Humans, Retrospective Studies, calcium, business.industry, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Staining, Mice, Inbred C57BL, Major duodenal papilla, Disease Models, Animal, Basic Research, 030104 developmental biology, biology.protein, ATP-Binding Cassette Transporters, Kidney stones, Tomography, X-Ray Computed, business
Abstract: Background Pseudoxanthoma elasticum (PXE) is a genetic disease caused by mutations in the ABCC6 gene that result in low pyrophosphate levels and subsequent progressive soft tissue calcifications. PXE mainly affects the skin, retina, and arteries. However, many patients with PXE experience kidney stones. We determined the prevalence of this pathology in patients with PXE and examined the possible underlying mechanisms in murine models. Methods We conducted a retrospective study in a large cohort of patients with PXE and analyzed urine samples and kidneys from Abcc6 −/− mice at various ages. We used Yasue staining, scanning electron microscopy, electron microscopy coupled to electron energy loss spectroscopy, and Fourier transform infrared microspectroscopy to characterize kidney calcifications. Results Among 113 patients with PXE, 45 (40%) had a past medical history of kidney stones. Five of six computed tomography scans performed showed evidence of massive papillary calcifications (Randall plaques). Abcc6 −/− mice spontaneously developed kidney interstitial apatite calcifications with aging. These calcifications appeared specifically at the tip of the papilla and formed Randall plaques similar to those observed in human kidneys. Compared with controls, Abcc6 −/− mice had low urinary excretion of pyrophosphate. Conclusions The frequency of kidney stones and probably, Randall plaque is extremely high in patients with PXE, and Abcc6 −/− mice provide a new and useful model in which to study Randall plaque formation. Our findings also suggest that pyrophosphate administration should be evaluated for the prevention of Randall plaque and kidney stones.
Published: 2018

23. High frequency and wide range of human kidney papillary crystalline plugs

Author: Marine Le Dudal, Marine Livrozet, Jean Philippe Haymann, Léa Huguet, Emmanuel Letavernier, Joëlle Perez, Isabelle Brocheriou, Michel Daudon, Dominique Bazin, Vincent Frochot, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pathologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), HAL-UPMC, Gestionnaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Calcium Phosphates, 0301 basic medicine, Urology, 030232 urology & nephrology, Calcium oxalate, chemistry.chemical_element, Calcium, engineering.material, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Kidney Calculi, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Spectroscopy, Fourier Transform Infrared, medicine, Loop of Henle, Humans, Amorphous calcium phosphate, Kidney Tubules, Collecting, Octacalcium phosphate, Aged, Magnesium phosphate, Chemistry, urogenital system, Anatomy, Middle Aged, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 030104 developmental biology, medicine.anatomical_structure, Microscopy, Electron, Scanning, Whitlockite, engineering, Kidney stones
Abstract: International audience; Most of kidney stones are supposed to originate from Randall's plaque at the tip of the papilla or from papillary tubular plugs. Nevertheless, the frequency and the composition of crystalline plugs remain only partly described. The objective was to assess the frequency, the composition and the topography of papillary plugs in human kidneys. A total of 76 papillae from 25 kidneys removed for cancer and without stones were analysed by immunohistochemistry combined with Yasue staining, field emission-scanning electron microscopy and Fourier transformed infrared micro-spectroscopy. Papillary tubular plugs have been observed by Yasue staining in 23/25 patients (92%) and 52/76 papillae (68%). Most of these plugs were made of calcium phosphate, mainly carbonated apatite and amorphous calcium phosphate, and rarely octacalcium phosphate pen-tahydrate. Calcium and magnesium phosphate (whitlockite) have also been observed. Based upon immunostaining coupled to Yasue coloration, most of calcium phosphate plugs were located in the deepest part of the loop of Henle. Calcium oxalate monohydrate and dihydrate tubular plugs were less frequent and stood in collecting ducts. At last, we observed calcium phosphate plugs deforming and sometimes breaking adjacent collecting ducts. Papillary tubular plugging, which may be considered as a potential first step toward kidney stone formation, is a very frequent setting, even in kidneys of non-stone formers. The variety in their composition and the distal precipitation of calcium oxalate suggest that plugs may occur in various conditions of urine supersaturation. Plugs were sometimes associated with collecting duct deformation.
Published: 2018

24. Reversal of Arterial Stiffness and Maladaptative Arterial Remodeling After Kidney Transplantation

Author: Erwan Bozec, Pierre Boutouyrie, Michel Delahousse, Marie Briet, Christophe Legendre, Jean Philippe Haymann, Alexandre Karras, Lawrence P. McMahon, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Monash University [Clayton], Hôpital Foch [Suresnes], Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), HAL UPMC, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Service de Physiologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Carotid Artery Diseases, Male, Time Factors, Nephrology and Kidney, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, 030204 cardiovascular system & hematology, Carotid Intima-Media Thickness, stiffness, 0302 clinical medicine, renal disease, Risk Factors, Vascular Disease, Living Donors, Prospective Studies, Pulse wave velocity, Kidney transplantation, Original Research, Middle Aged, Allografts, 3. Good health, [SDV] Life Sciences [q-bio], Carotid Arteries, Treatment Outcome, Cardiology, Female, Cardiology and Cardiovascular Medicine, Adult, medicine.medical_specialty, vascular remodeling, Renal function, Pulse Wave Analysis, vascular function, 03 medical and health sciences, Vascular Stiffness, Internal medicine, medicine, Humans, Organ donation, Renal Insufficiency, Chronic, Chi-Square Distribution, Kidney in Cardiovascular Disease, [ SDV ] Life Sciences [q-bio], business.industry, medicine.disease, Kidney Transplantation, Confidence interval, Surgery, Transplantation, Multivariate Analysis, Arterial stiffness, business, transplantation, Kidney disease
Abstract: Background Chronic kidney disease is characterized by stiffening, thinning, dilatation, and increased circumferential wall stress of large arteries, associated with increased cardiovascular risk. Kidney transplantation ( KT ) reverses many pathological features of chronic kidney disease and improves life expectancy; however, longitudinal studies exploring the impact of KT on recipient large arteries are scarce. Methods and Results This study was designed to appraise arterial changes following KT . Carotid‐femoral pulse wave velocity, carotid remodeling (circumferential wall stress and carotid internal diameter), and stiffness were measured in 161 consecutive recipients receiving either a living (n=49) or a deceased (n=112) donor allograft, at 3 and 12 months after transplantation. Mean pulse wave velocity decreased from 10.8 m/s (95% confidence interval, 10.5–11.2 m/s) (at month 3) to 10.1 m/s (95% confidence interval, 9.8–10.5 m/s) (at month 12) ( P KT ( P P KT ( P Conclusions Large‐artery stiffness and maladaptive carotid artery remodeling of chronic kidney disease is partially reversed within 12 months of KT and appears unrelated to renal function. Improvements were independently associated with live organ donation. Our data suggest that expanded criteria donors may hamper vascular recovery.
Published: 2017

25. Respective influence of calcium and oxalate urine concentration on the formation of calcium oxalate monohydrate or dihydrate crystals

Author: Dominique Bazin, Paul Jungers, Vincent Frochot, Jean-Philippe Haymann, Emmanuel Letavernier, Michel Daudon, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie et Dialyses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), HAL-UPMC, Gestionnaire, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Chemistry(all), General Chemical Engineering, education, Inorganic chemistry, 030232 urology & nephrology, Calcium/oxalate ratio, chemistry.chemical_element, Urine, Calcium, engineering.material, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Oxalate, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Crystalluria, medicine, Whewellite, Weddellite, General Chemistry, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, chemistry, 030220 oncology & carcinogenesis, engineering, Chemical Engineering(all), medicine.symptom, Stone formers, Calcium oxalate molar product, CALCIUM OXALATE MONOHYDRATE
Abstract: Clinical interest for the identification of the crystalline phase of CaOx, either monohydrate (COM) or dihydrate (COD), in crystalluria analysis is debated. In the present study, we simultaneously determined calcium and oxalate concentration and identified the two crystalline phases of CaOx crystals in 1288 first morning urine samples from 407 CaOx stone formers with crystalluria.The mean concentration of oxalate ions was higher in urine samples containing COM than in those containing COD crystals, and conversely the mean concentration of calcium ions was markedly higher in urine samples containing COD than in those containing COM crystals. COM crystals were predominant (93%) in urine samples with a Ca/Ox molar ratio 14 (i.e. markedly hypercalciuric). In the intermediate Ca/Ox values, mixed COD and COM crystals were present. Logistic regression analysis showed that increasing the concentration of calcium resulted in a higher risk of COD than of COM crystal formation, whereas increasing oxalate concentration was associated with a greater COM than COD crystal formation. In conclusion, this study demonstrates the calcium-dependence of COD and the oxalate-dependence of COM crystal formation. Thus, a crystalluria mainly composed of COD suggests a search for conditions associated with hypercalciuria whereas an abundant crystalluria made of COM crystals should prompt a search for heavy hyperoxaluria and noteworthy primary hyperoxaluria.
Published: 2016

26. Nephrotoxicity induced by drugs: The case of foscarnet and atazanavirdA SEM and mFTIR investigation

Author: Vincent Frochot, Jean-Philippe Haymann, Emmanuel Letavernier, Chantal Jouanneau, Michel Daudon, Dominique Bazin, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), HAL-UPMC, Gestionnaire, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Foscarnet, Pathology, medicine.medical_specialty, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Chemistry(all), General Chemical Engineering, 030106 microbiology, Kidney biopsy, Lumen (anatomy), Nephron, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Nephrotoxicity, Atazanavir, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, medicine, Von Kossa stain, Triamterene, Infrared microscopy, Chemistry, virus diseases, General Chemistry, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Crystallography, medicine.anatomical_structure, Chemical Engineering(all), Drug-induced renal failure, Crystal deposits, medicine.drug
Abstract: Biopsies of native or transplanted kidneys in patients suffering chronic or acute renal failure are commonly stained for tissue examination and search for possible crystal deposits which are then identified by polarizing microscopy and staining by von Kossa's method revealing mainly calcium deposits. Renal biopsies presumably containing crystal deposits were analyzed with a Spotlight 400 μFTIR (Fourier Transform Infra Red) imaging system in the mid-infrared spectral range to obtain infrared maps of tissue slides at high spatial resolution, down to 10 microns. When required, an optional ATR imaging accessory was used, improving the spatial resolution by a factor four, down to 3 microns at 1000 cm−1. Among the 685 renal biopsies, 72% contained abnormal non-proteic material. Among them, 2.16% contained drug crystals (triamterene, N-acetylsulfadiazine, ciprofloxacine, indinavir, atazanavir, foscarnet, and vancomycine). We focused on foscarnet and atazanavir deposits. In the case of foscarnet-induced renal failure, two types of crystals were found in one patient. They were located in different parts of the nephron: sodium and/or calcium phosphonoformate crystals within glomerules and carbapatite in the proximal tubular cells. By contrast, atazanavir was only found in the tubular lumen of the nephron.A precise identification of crystal deposits is essential for the diagnosis of an unexplained renal failure. Common histological procedures clearly fail to identify crystals deposits accurately. In most cases, light and polarizing microscopic examination should be completed by FTIR analysis.
Published: 2016

27. The role of physicochemistry in urology and nephrology, selected results obtained during the last ten years

Author: Jean-Philippe Haymann, Emmanuel Letavernier, Michel Daudon, P Meria, Dominique Bazin, Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Urologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Synchrotron radiation, Physicochemistry, 010405 organic chemistry, business.industry, Urology, Large-scale instruments, Rayonnement synchrotron, Grands instruments, 010402 general chemistry, 01 natural sciences, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, 0104 chemical sciences, Nephrology, Medicine, Physicochimie, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Néphrologie, business, Urologie, Humanities
Abstract: International audience; Introduction: The presence of pathological calcifications, which can be either concretions or ectopic call for physicochemical characterisation techniques in order to define a significant diagnosis. The aim of this review is to present a set of characterisation techniques able to describe at the micrometer scale their structural and chemical characteristics and show their place at the hospital.Method: Results already published in the last ten years based on characterisation techniques present in laboratories or specific to large-scale instruments are presented. Their usefulness for the clinician is discussed.Results: The presence and role of heavy metals in urinary stones through data collected through μX-ray fluorescence is debated. If these data suggest a simple substitution process of calcium, recent data suggest that weddellite is associated to a Zn-rich environment, partly favoured by an inflammation process. Investigation on the chemistry and the structure of unusual deposits in kidney biopsies show a great chemical diversity of ectopic calcifications. Such diversity shows that staining procedures to characterize such deposits are obsolete. Finally, several diseases which can be assessed through techniques specific to large-scale instruments and defined by the clinician are presented.Conclusion: The chemical and structural complexity of pathological calcifications call for a characterization through physicochemical techniques. Only such approach allows the clinician to define a significant diagnosis and to care the patient.; Introduction: Les calcifications pathologiques rénales qu’elles s’apparentent à des concrétions ou à des calcifications tissulaires impliquent de savoir déterminer correctement les composés chimiques qui les composent afin de porter un diagnostic menant à une prise en charge adéquate. Le but de cet article de revue est de dépeindre les techniques physicochimiques aptes à réaliser cette caractérisation structurale et chimique à l’échelle du micromètre et de montrer leur insertion au sein même de l’hôpital.Méthode: Les résultats acquis ces dix dernières années utilisant des techniques de caractérisation de laboratoire ou spécifiques aux grands instruments comme le synchrotron Soleil ou le laboratoire Léon-Brillouin sont présentés. Leur pertinence dans l’activité du clinicien a été examinée.Résultats: Le rôle des éléments traces dans la pathogenèse des calculs rénaux au travers de données acquises par fluorescence X est discuté. Si leurs propriétés catalytiques ne sont pas confirmées par les données expérimentales, l’analyse fine a dévoilé certaines particularités intéressantes concernant les teneurs en Zn des deux composés d’oxalate de calcium, i.e. whewellite et weddellite. En effet, les calculs de weddellite présentent des bipyramides aux angles et arêtes vifs susceptibles d’induire une inflammation tissulaire. L’analyse morphoconstitutionnelle des biopsies rénales dévoile une grande diversité chimique puisque 22 corps différents ont été identifiés. Cette diversité indique que les méthodes de coloration dont l’anatomopathologiste dispose sont insuffisantes pour caractériser ces corps. Enfin, nous énumérons différentes problématiques abordées par les grands instruments et définies par le clinicien.Conclusion: La complexité structurale et la diversité chimique des calcifications pathologiques invitent à la mise en œuvre de techniques de caractérisation physicochimiques. Seule cette approche permet au clinicien la pose d’un diagnostic fiable et donc une prise en charge adéquate du patient.
Published: 2016

28. Topographie, composition et analyse à l’échelle nanoscopique des plaques de Randall débutantes

Author: Marie-Christine Verpont, Alexandre Gloter, E. Letavernier, Vincent Frochot, Jean-Philippe Haymann, Léa Huguet, Isabelle Brocheriou, Olivier Traxer, Michel Daudon, Dominique Bazin, O. Stephan, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'urologie [CHU Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), HAL-UPMC, Gestionnaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Anatomie et cytologie pathologiques [CHU Tenon], and Service d'Urologie [CHU Tenon]
Subjects: 03 medical and health sciences, 0302 clinical medicine, Nephrology, 030232 urology & nephrology, 030204 cardiovascular system & hematology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
Abstract: International audience; Alexander Randall a identifié dans les années 1930 des dépôts de phosphate de calcium à la pointe des papilles rénales comme étant à l’origine des calculs rénaux oxalocalciques : les plaques de Randall. Huit décennies plus tard, nous observons à un nombre croissant de calculs générés à partir de ces plaques. Nous avons considéré que l’analyse de plaques « débutantes » pourrait permettre de déterminer leur origine.
Published: 2016

29. New insights into the presence of sodium hydrogen urate monohydrate in Randall's plaque

Author: Chantal Jouanneau, Jean-Philippe Haymann, Dominique Bazin, Michel Daudon, Emmanuel Véron, Christophe Sandt, Pierre Ronco, Olivier Traxer, Paul Dumas, Pierre Conort, Guy Matzen, Emmanuel Letavernier, Administateur, HAL Sorbonne Université, Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Conditions Extrêmes et Matériaux : Haute Température et Irradiation (CEMHTI), Université d'Orléans (UO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service d'Urologie [CHU Tenon], Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'urologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université d'Orléans (UO)
Subjects: 0301 basic medicine, Chemistry(all), General Chemical Engineering, Renal parenchyma, Sodium, 030232 urology & nephrology, Diuresis, chemistry.chemical_element, Calcium, Apatite, Environmental scanning electron microscopy, 03 medical and health sciences, 0302 clinical medicine, Calcium phosphate apatite, [CHIM] Chemical Sciences, medicine, [CHIM]Chemical Sciences, Kidney stone, Synchrotron radiation-μFourier Transform Infra Red spectroscopy, Chemistry, Calcium oxalate nephrolithiasis, General Chemistry, medicine.disease, Sodium hydrogen urate monohydrate, 3. Good health, Major duodenal papilla, Crystallography, 030104 developmental biology, Biochemistry, Randall's plaque, visual_art, visual_art.visual_art_medium, Chemical Engineering(all), Kidney stones
Abstract: International audience; Calcium oxalate nephrolithiasis is a common ailment. Frequent risk factors associated with are low diuresis, dietary imbalance, inherited or acquired metabolic disorders. Another important factor, namely the presence of a mineral deposit made of apatite at the surface of the papilla, named Randall's plaque (RP), has been recently underlined. In most cases, RP which serves as a nidus for kidney stone formation is made of calcium phosphate apatite (CA). However, RP does not seem to be composed exclusively of CA. We would like to assess the case of RP where sodium hydrogen urate monohydrate (NaUr) is also present in its chemical composition. To attain this goal, a set of experiments including Environmental Scanning Electron Microscopy (ESEM) and Synchrotron Radiation Fourier Transform InfraRed (SR-FTIR) has been performed to analyze papillae of six kidneys randomly selected after they were surgically removed for cancer. NaUr crystals were found in two samples. We show through ESEM an usual morphology of RP present at the surface of kidney stones in the presence of NaUr. Moreover, we discuss the presence of NaUr in the renal parenchyma and its spatial repartition with CA. The complete set of data indicates that different biochemical mechanisms are probably involved in the pathogenesis of RP. The next step will be to establish a significant relationship between these physicochemical data and the clinical and biochemical data of the patients.
Published: 2016

30. Urolithiasis: What can we learn from a Nature which dysfunctions?

Author: Jacques Livage, Vincent Frochot, Jean-Philippe Haymann, Emmanuel Letavernier, Dominique Bazin, Ali Abou-Hassan, Guillaume Laffite, David Portehault, Frederik Tielens, Michel Daudon, Christian Bonhomme, Laure Bonhomme, Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Matériaux Hybrides et Nanomatériaux (MHN), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), HAL UPMC, Gestionnaire, Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)
Subjects: Cognitive science, [PHYS]Physics [physics], Chemistry(all), Computer science, General Chemical Engineering, Janus particles, Nanotechnology, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Biomimetism, 0104 chemical sciences, [PHYS] Physics [physics], Urolithiasis, Chemical Engineering(all), [CHIM.CRIS]Chemical Sciences/Cristallography, [CHIM.CRIS] Chemical Sciences/Cristallography, 0210 nano-technology
Abstract: International audience; Learning from Mother Nature constitutes a major intellectual movement encompassing music, architecture and chemistry. In this contribution, we would like to assess the symmetry and the interface present in pathological calcifications in order to propose a bio-inspired approach. We present an overview on the observations made on kidney stone growth at the macroscopic scale. The results are discussed at the molecular scale and examples are proposed to implement the biological asymmetrical growth in pathological calcifications in biomimetic strategies such as in in vitro microfluidic experiments.
Published: 2016

31. Combining field effect scanning electron microscopy, deep UV fluorescence, Raman, classical and synchrotron radiation Fourier transform Infra-Red Spectroscopy in the study of crystal-containing kidney biopsies

Author: Christophe Sandt, Pierre Ronco, Paul Dumas, Arnaud Dessombz, Sergio Bertazzo, Jean-Philippe Haymann, Emmanuel Letavernier, Matthieu Réfrégiers, Joni Frederick, Michel Daudon, Chantal Jouanneau, Dominique Bazin, Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Materials, Imperial College London, Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Administateur, HAL Sorbonne Université, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Chemistry(all), General Chemical Engineering, 030232 urology & nephrology, Analytical chemistry, Energy-dispersive X-ray spectroscopy, Kidney biopsy, engineering.material, 010402 general chemistry, 01 natural sciences, Deep UV visible, law.invention, Synchrotron, Crystal, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, law, [PHYS.PHYS] Physics [physics]/Physics [physics], Brushite, Fourier transform infrared spectroscopy, Spectroscopy, Field effect scanning electron microscopy, Raman, [PHYS.PHYS]Physics [physics]/Physics [physics], Chemistry, General Chemistry, 0104 chemical sciences, FTIR, Chemical Engineering(all), symbols, engineering, Raman spectroscopy, Weddellite
Abstract: International audience; Crystal formation in kidney tissue is increasingly recognized as a major cause of severe or acute renal failure. Kidney biopsies are currently performed and analyzed using different staining procedures. Unfortunately, none of these techniques are able to distinguish the different Ca phosphates (e.g., amorphous or nanostructured Ca phosphate apatite, octacalcium phosphate, brushite…) or Ca oxalates (whewellite and weddellite). Moreover, the crystal’s morphology, a structural parameter proven as a major information to the clinician regarding kidney stones, is not taken into account. Such major limitations call for a different research approach, based on physicochemical techniques. Here we propose classical observations through field-emission scanning electron microscopy experiments combined with energy dispersive spectroscopy as well as measurements through Raman and μFourier transform Infra-Red Spectroscopy. If necessary, in the case of microcrystals, observations using cutting edge technology such as Synchrotron Radiation (SR) – FTIR or SR-UV visible spectroscopy can be subsequently performed on the same sample. Taken together this set of diagnostic tools will help clinicians gather information regarding the nature and the spatial distribution at the subcellular scale of different chemical phases present in kidney biopsies as well as on the crystal morphology and therefore obtain more precise diagnosis.
Published: 2016

32. Calcium oxalate precipitation by diffusion using laminar microfluidics: toward a biomimetic model of pathological microcalcifications

Author: Laure Bonhomme-Coury, César Leroy, Michel Daudon, Dominique Bazin, Ivan T. Lucas, Stéphan Rouzière, G. Laffite, Christian Bonhomme, Ali Abou-Hassan, Vincent Frochot, Jean-Philippe Haymann, Emmanuel Letavernier, Florence Babonneau, PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interfaces et Systèmes Electrochimiques (LISE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Labex Matisse Labex MICHEM, ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Surface Properties, Microfluidics, 030232 urology & nephrology, Biomedical Engineering, Calcium oxalate, chemistry.chemical_element, Mineralogy, Bioengineering, 02 engineering and technology, Calcium, Kidney, Biochemistry, Oxalate, Diffusion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Biomimetics, Microfluidic channel, Chemical Precipitation, Humans, [CHIM]Chemical Sciences, Particle Size, Calcium Oxalate, Precipitation (chemistry), Calcinosis, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], Laminar flow, General Chemistry, [CHIM.MATE]Chemical Sciences/Material chemistry, Microfluidic Analytical Techniques, 021001 nanoscience & nanotechnology, chemistry, Chemical engineering, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Particle size, 0210 nano-technology
Abstract: International audience; The effect of mixing calcium and oxalate precursors by diffusion at miscible liquid interfaces on calcium oxalate crystalline phases, and in physiological conditions (concentrations and flow rates), is studied using a microfluidic channel. This channel has similar dimensions as the collection duct in human kidneys and serves as a biomimetic model in order to understand the formation of pathological microcalcifications.
Published: 2016

33. Comprehensive morpho-constitutional analysis of urinary stones improves etiological diagnosis and therapeutic strategy of nephrolithiasis

Author: Vincent Frochot, Jean-Philippe Haymann, Michel Daudon, Dominique Bazin, Emmanuel Letavernier, Arnaud Dessombz, Paul Jungers, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), d'Eggis, Gilles, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service des Explorations Fonctionnelles, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Laboratoire de Physique des Solides ( LPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé ( SMiLES ), Laboratoire de Chimie de la Matière Condensée de Paris ( LCMCP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Collège de France ( CdF ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Collège de France ( CdF ) -Centre National de la Recherche Scientifique ( CNRS ), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Morphology, medicine.medical_specialty, Chemistry(all), Etiology, General Chemical Engineering, Urinary system, 030232 urology & nephrology, Calcium oxalate, Urine, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Primary hyperoxaluria, 03 medical and health sciences, chemistry.chemical_compound, [ CHIM.CRIS ] Chemical Sciences/Cristallography, 0302 clinical medicine, Distal renal tubular acidosis, Urolithiasis, Internal medicine, medicine, [CHIM.CRIS]Chemical Sciences/Cristallography, Hypercalciuria, [CHIM.CRIS] Chemical Sciences/Cristallography, Drugs, General Chemistry, Morpho-constitutional analysis, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Steatorrhea, chemistry, Biochemistry, Calcium phosphate, Purines, 030220 oncology & carcinogenesis, Chemical Engineering(all), Uric acid, Cystine, medicine.symptom, Stone analysis
Abstract: International audience; The generalized use of physical methods, X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) decisively improved urinary stone analysis by allowing to accurately identify the chemical nature, crystalline phases and relative proportions of stone constituents. Such compositional analysis is sufficient to identify stone diseases involving a single specific component such as cystine, 2,8-dihydroxyadenine (DHA), struvite, uric acid, ammonium hydrogen urate or a drug. However, for common calcium nephrolithiasis, which represents by far the largest part of urinary stones throughout the world, the simple identification of calcium oxalate (CaOx) and/or calcium phosphate (CaP) as constituents provides incomplete etiologic information because a same elemental stone composition may result from different lithogenic processes.A more comprehensive method combining careful morphologic examination of the surface and the section of stones with detailed FTIR analysis of the nature, location, crystalline phases and a respective proportion of stone constituents, therefore termed ‘morpho-constitutional’ analysis, as used in our laboratory for four decades provides more complete etiologic information. In common idiopathic CaOx nephrolithiasis, the predominance of the monohydrate form (COM) was shown to be associated with elevated urine Ox concentration, whereas the dihydrate form (COD) was associated with hypercalciuria, thus orienting dietary and/or pharmacological intervention. A major contribution of the method is to immediately orient the diagnosis of rare, but severe, diseases leading to a loss of renal function, when stone analysis reveals a peculiar morphology of common constituents. The most salient examples are the type Ic morphology of COM stones, pathognomonic of primary hyperoxaluria, type Ie morphology, which is highly suggestive of absorptive hyperoxaluria as seen in inflammatory bowel diseases and pathologies inducing steatorrhea, type IIId morphology of ammonium urate stones, which orientates towards chronic diarrhea with dietary imbalance and loss of electrolytes, and type IVa2 morphology of carbapatite, specific of distal renal tubular acidosis of congenital or acquired origin, and distinctive aspect of 2,8-DHA stones. In conclusion, the proposed morpho-constitutional method should be recommended for routine stone analysis, inasmuch as it is simple, rapid, reliable, clinically relevant and cost-effective.
Published: 2016

34. Topography, composition and structure of incipient Randall’s plaque at the nanoscale level

Author: Vincent Frochot, Léa Huguet, Olivier Traxer, Isabelle Brocheriou, Dominique Bazin, Marie-Christine Verpont, Cécile Verrier, Odile Stéphan, Alexandre Gloter, Jean-Philippe Haymann, Emmanuel Letavernier, Michel Daudon, HAL-UPMC, Gestionnaire, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Urologie [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pathologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Urologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Service d'urologie [CHU Tenon]
Subjects: 0301 basic medicine, Urology, kidney stones, 030232 urology & nephrology, engineering.material, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Phosphates, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Loop of Henle, medicine, Humans, Amorphous calcium phosphate, Von Kossa stain, Aged, phosphate, Kidney Medulla, calcium, business.industry, urogenital system, Calcinosis, Vasa recta, Anatomy, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Randall's plaque, Transmission electron microscopy, Microscopy, Electron, Scanning, Whitlockite, engineering, Kidney Diseases, Kidney stones, Electron microscope, Crystallization, business
Abstract: International audience; PurposeAlexander Randall identified calcium phosphate plaques in renal papillae as the origin of kidney stones. However, little is known about the early steps of Randall’s plaque formation, preceding the onset of urolithiasis. Our objectives were to characterize the composition and the initial formation site of incipient Randall’s plaque in non-stone formers living patients.Material and MethodsMedian age of the patients was 67.7 years. Fifty-four healthy papillae from kidneys removed for cancer and without stones have been analyzed by immunohistochemistry and Von Kossa staining, Field Emission-Scanning Electron Microscopy with Energy Dispersive X-ray analysis, μ-Fourier Transform Infrared Spectroscopy, Cryo-Transmission Electron Microscopy coupled to Selected-Area Electron Diffraction and Electron Energy Loss Spectroscopy.ResultsIncipient Randall’s plaque has been observed in 72.7% of kidneys. Carbonated apatite was as expected the main component of microcalcifications but amorphous calcium phosphate and whitlockite have been identified in 80% and 40% of the papillae, respectively. Incipient plaques stood in the deepest part of the papillae, around the loop of Henle tip but also around vasa recta (respectively 62.4 % and 37.2 % of microcalcifications) and rarely close to collecting ducts. At the nanoscale level, incipient calcifications were often made of several nanocrystals inside organic material looking like microvesicles.ConclusionsIncipient Randall’s plaque is frequent and appears at the extreme tip of renal papillae, around the hairpin structure of the loop of Henle but also around vasa recta. Nanoscale analyses suggest a local nucleation process promoting nanocrystal growth in a supersaturated milieu. In addition, plaques contain various calcium and magnesium phosphates and not only carbonated apatite.
Published: 2016

35. How to assess the role of Pt and Zn in the nephrotoxicity of Pt anti-cancer drugs?: An investigation combining mXRF and statistical analysis. Part II: Clinical application

Author: Emmanuel Esteve, Michel Daudon, John J. Rehr, Pierre Ronco, Alexandre Hertig, Christian Mocuta, Alex Kellum, Eric Rondeau, Emmanuel Letavernier, Dominique Bazin, Jean Philippe Haymann, Aurélien Bataille, Karine Provost, Kris Jorissen, Stéphan Rouzière, Solenn Reguer, Chantal Jouanneau, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie et des Matériaux Paris-Est (ICMPE), Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), University of Washington [Seattle], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and HAL UPMC, Gestionnaire
Subjects: 0301 basic medicine, 030103 biophysics, Chemistry(all), General Chemical Engineering, Nanotechnology, Pt-based anti-cancer drugs X-ray fluorescence, Nephrotoxicity, Synchrotron, 03 medical and health sciences, 0302 clinical medicine, Ototoxicity, [CHIM] Chemical Sciences, Biopsy, Medicine, Distribution (pharmacology), [CHIM]Chemical Sciences, Statistical analysis, medicine.diagnostic_test, business.industry, Neurotoxicity, General Chemistry, medicine.disease, 3. Good health, Oxaliplatin, 030220 oncology & carcinogenesis, Toxicity, Chemical Engineering(all), Cancer research, business, medicine.drug
Abstract: International audience; In this contribution, an approach developed previously for mice is used for human biopsy. In the case of patient 1, Pt detection is performed 6 days after the last oxaliplatin infusion, while for patient 2, the biopsy was performed more than 15 days after his first platin infusion and several dialysis. Even for these biological samples, experiments show that synchrotron mediated mXRF is a suitable tool to detect Pt in kidney biopsy, and thus probably for any organ exposed to Pt. Therefore, mXRF could also be of major interest to decipher the mechanism beyond Pt induced neurotoxicity, ototoxicity on human biopsy. Pharmacoavailability of chemotherapies is a major concern because some treatment failures are explained by poor tumor penetration of the active molecule. mXRF could be an elegant way to map the distribution of Pt inside cancerous cells at the micrometer scale. Pt and Zn are only two of the numerous trace elements that mXRF can detect; heavy metal intoxication diagnosis and the toxicity mechanism probably could also benefit from this innovative technique.
Published: 2016

36. Low Serum Creatine Kinase Level Predicts Mortality in Patients with a Chronic Kidney Disease

Author: Adrien Flahault, Marie Metzger, Jean-François Chassé, Jean-Philippe Haymann, Jean-Jacques Boffa, Martin Flamant, François Vrtovsnik, Pascal Houillier, Bénédicte Stengel, Eric Thervet, Nicolas Pallet, NephroTest study group, Centre interdisciplinaire de recherche en biologie (CIRB), Collège de France (CdF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-PSL Research University (PSL)-Centre National de la Recherche Scientifique (CNRS), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de recherche en épidémiologie et santé des populations (CESP), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris Descartes - Paris 5 (UPD5), Dpt Clinical chemistry [CHU Pompidou], Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie et Dialyses [CHU Tenon], Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Service d'explorations fonctionnelles [CHU Pompidou], Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre interdisciplinaire de recherche en biologie ( CIRB ), Collège de France ( CdF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), CHU Tenon [APHP]-Assistance publique - Hôpitaux de Paris - AP-HP (FRANCE), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Male, Physiology, 030232 urology & nephrology, lcsh:Medicine, Blood Pressure, 030204 cardiovascular system & hematology, Biochemistry, Vascular Medicine, Gastroenterology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Cohort Studies, chemistry.chemical_compound, Endocrinology, 0302 clinical medicine, Chronic Kidney Disease, Medicine and Health Sciences, lcsh:Science, Creatine Kinase, 2. Zero hunger, education.field_of_study, Multidisciplinary, Hazard ratio, Drugs, Middle Aged, Nephrology, Creatinine, Female, Research Article, Glomerular Filtration Rate, medicine.medical_specialty, Endocrine Disorders, Death Rates, Population, Renal function, 03 medical and health sciences, Population Metrics, Albumins, Internal medicine, Diabetes Mellitus, medicine, Humans, Risk factor, education, Serum Albumin, Aged, Proportional Hazards Models, Demography, Pharmacology, Renal Physiology, Population Biology, Proportional hazards model, business.industry, lcsh:R, Statins, Biology and Life Sciences, Proteins, medicine.disease, chemistry, Metabolic Disorders, People and Places, Kidney Failure, Chronic, lcsh:Q, business, Body mass index, Biomarkers, Kidney disease
Abstract: NephroTest study group; International audience; BackgroundSerum creatine kinase (sCK) reflects CK activity from striated skeletal muscle. Muscle wasting is a risk factor for mortality in patients with chronic kidney disease (CKD). The aim of this study is to evaluate whether sCK is a predictor of mortality and end-stage renal disease (ESRD) in a CKD population.MethodsWe included 1801 non-dialysis-dependent CKD patients from the NephroTest cohort. We used time-fixed and time-dependent cause-specific Cox models to estimate hazard ratios (HRs) for the risk of death and for the risk of ESRD associated with gender-specific sCK tertiles.ResultsHigher sCK level at baseline was associated with a lower age, a higher body mass index, and a higher level of 24 h urinary creatinine excretion, serum albumin and prealbumin (p
Published: 2016

37. Demographics and Characterization of 10,282 Randall Plaque-Related Kidney Stones: A New Epidemic?

Author: Sophie Vandermeersch, Pierre Ronco, Olivier Traxer, Jean-Philippe Haymann, Emmanuel Letavernier, Michel Daudon, Mohamed Tligui, Laurent Baud, CHU Tenon [APHP], Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, Calcium Phosphates, Male, medicine.medical_specialty, Demographics, MEDLINE, Calcium oxalate, Observational Study, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Article, chemistry.chemical_compound, Kidney Calculi, Risk Factors, Internal medicine, medicine, Humans, Aged, Calcium Oxalate, business.industry, Incidence (epidemiology), General Medicine, Middle Aged, medicine.disease, 3. Good health, Surgery, chemistry, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Kidney stones, Female, France, business
Abstract: Supplemental Digital Content is available in the text, Renal stone incidence has progressively increased in industrialized countries, but the implication of Randall plaque in this epidemic remains unknown. Our objectives were to determine whether the prevalence of Randall plaque-related stones increased during the past decades after having analyzed 30,149 intact stones containing mainly calcium oxalate since 1989 (cross-sectional study), and to identify determinants associated with Randall plaque-related stones in patients (case–control study). The proportion of Randall plaque-related stones was assessed over 3 time periods: 1989–1991, 1999–2001, and 2009–2011. Moreover, we analyzed clinical and biochemical parameters of 105 patients affected by calcium oxalate stones, with or without plaque. Of 30,149 calcium oxalate stones, 10,282 harbored Randall plaque residues (34.1%). The prevalence of Randall plaque-related stones increased dramatically during the past years. In young women, 17% of calcium oxalate stones were associated with Randall plaque during the 1989–1991 period, but the proportion rose to 59% 20 years later (P
Published: 2015

38. Calcium Phosphate Stone Morphology Can Reliably Predict Distal Renal Tubular Acidosis

Author: Arnaud Dessombz, Jean-Philippe Haymann, Emmanuel Letavernier, Dominique Bazin, Michel Daudon, Administateur, HAL Sorbonne Université, Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Physique des Solides ( LPS ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Laboratoire de Chimie de la Matière Condensée de Paris ( LCMCP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Collège de France ( CdF ) -Centre National de la Recherche Scientifique ( CNRS ), and Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE)
Subjects: Calcium Phosphates, medicine.medical_specialty, kidney, diagnosis, Urology, Urinary system, chemistry.chemical_element, Calcium, Stone analysis, Medullary sponge kidney, Gastroenterology, calcium phosphate, Kidney Calculi, Distal renal tubular acidosis, Predictive Value of Tests, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, medicine, Humans, Stone composition, Acidosis, Kidney, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, renal tubular, Reproducibility of Results, Acidosis, Renal Tubular, medicine.disease, 3. Good health, Endocrinology, medicine.anatomical_structure, chemistry, acidosis, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, nephrolithiasis
Abstract: International audience; PurposeCalcium stones represent 85% to 90% of all urinary calculi, including various crystalline compositions and etiological conditions. Calcium phosphate accounts for 10% to 15% of cases. These stones are mainly related to 3 groups of risk factors, including calcium or phosphate metabolism disturbance, renal acidification defects and urinary tract infection. Identifying the stone etiology often requires extensive metabolic evaluation. We assessed whether stone analysis including morphological typing in addition to stone composition could be a valuable help for diagnosis.Materials and MethodsOf 60,564 stones analyzed by morphological examination and infrared spectroscopy at our laboratory 6,439 (10.6%) were mainly composed of carbapatite. Of these stone 1,093 patients were included in study who had an available etiological diagnosis and stones containing at least 70% of calcium phosphate without struvite.ResultsOf the 1,093 calcium phosphate stones 12.8% showed a peculiar morphology termed IVa2, characterized by a smooth aspect and a glazed brown-yellow appearance with tiny cracks. IVa2 morphology was observed in 96.1% of stones associated with inherited distal renal tubular acidosis. In contrast, the other stones of similar composition but different morphology were related to distal renal tubular acidosis in only 3.9% of cases. In addition, IVa2 stones were found in 65% of calcium phosphate stone formers associated with Sjögren syndrome and in 35% of calcium phosphate stones in patients with medullary sponge kidney. These 2 conditions are related to a mild to moderate distal acidification defect.ConclusionsIdentifying IVa2 stone morphology is clinically relevant because it should prompt clinicians to search for complete or incomplete distal acidosis and initiate specific therapy to decrease recurrence.
Published: 2015

39. Decrease in urinary creatinine excretion in early stage chronic kidney disease

Author: Elena Tynkevich, Martin Flamant, Jean-Philippe Haymann, Marie Metzger, Eric Thervet, Jean-Jacques Boffa, François Vrtovsnik, Pascal Houillier, Marc Froissart, Bénédicte Stengel, NephroTest Study Group, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Physiologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Male, Muscle Physiology, Physiology, Epidemiology, 030232 urology & nephrology, lcsh:Medicine, Urine, 030204 cardiovascular system & hematology, Kidney Function Tests, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Body Mass Index, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Chronic Kidney Disease, Medicine and Health Sciences, Ethnicity, Medicine, Clinical Epidemiology, Public and Occupational Health, Prospective Studies, lcsh:Science, Musculoskeletal System, 2. Zero hunger, education.field_of_study, Multidisciplinary, Proteinuria, Muscles, Age Factors, Muscle Biochemistry, Organ Size, Nephrology, Creatinine, Female, Anatomy, medicine.symptom, Research Article, Glomerular Filtration Rate, medicine.medical_specialty, Urinary system, Population, Urology, Renal function, Excretion, 03 medical and health sciences, Sex Factors, Internal medicine, Humans, Renal Insufficiency, Chronic, Muscle, Skeletal, education, Nutrition, Renal Physiology, business.industry, Malnutrition, lcsh:R, Biology and Life Sciences, Renal System, medicine.disease, Biomarker Epidemiology, Endocrinology, chemistry, lcsh:Q, business, Kidney disease
Abstract: NephroTest Study Group; International audience; BACKGROUND:Little is known about muscle mass loss in early stage chronic kidney disease (CKD). We used 24-hour urinary creatinine excretion rate to assess determinants of muscle mass and its evolution with kidney function decline. We also described the range of urinary creatinine concentration in this population.METHODS:We included 1072 men and 537 women with non-dialysis CKD stages 1 to 5, all of them with repeated measurements of glomerular filtration rate (mGFR) by (51)Cr-EDTA renal clearance and several nutritional markers. In those with stage 1 to 4 at baseline, we used a mixed model to study factors associated with urinary creatinine excretion rate and its change over time.RESULTS:Baseline mean urinary creatinine excretion decreased from 15.3 ± 3.1 to 12.1 ± 3.3 mmol/24 h (0.20 ± 0.03 to 0.15 ± 0.04 mmol/kg/24 h) in men, with mGFR falling from ≥ 60 to
Published: 2014

40. Présence de cristaux sur les biopsies de greffons rénaux : fréquence, étiologie et pronostic

Author: Marie Frimat, Michel Daudon, A. Garstka, Viviane Gnemmi, Arnaud Lionet, Dominique Bazin, M. Haeck, Jean-Philippe Haymann, Christian Noel, Hôpital Claude Huriez [Lille], CHU Lille, Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Nephrology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Bien que la présence de cristaux tubulo-interstitiels au sein de biopsies de greffon rénaux soit décrite, leur signification reste imprécise [1] and [2]. L’objectif de ce travail rétrospectif et monocentrique était donc de définir leur fréquence, leur étiologie et leur impact pronostique.
Published: 2014

41. The Relation of Hepcidin to Iron Disorders, Inflammation and Hemoglobin in Chronic Kidney Disease

Author: Bénédicte Stengel, François Vrtovsnik, Lucile Mercadel, Martin Flamant, Marie Metzger, Marc Froissart, Eric Thervet, Jean-Jacques Boffa, Jean Philippe Haymann, Pascal Houillier, Service d'Urologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Pierre et Marie Curie - Paris 6 (UPMC), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM U699, Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), HAL UPMC, Gestionnaire, Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], Service d'urologie, néphrologie et transplantation [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service de Physiologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: Male, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Hemoglobins, 0302 clinical medicine, hemic and lymphatic diseases, Chronic Kidney Disease, Medicine and Health Sciences, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Anemia, Iron-Deficiency, biology, Anemia, Iron deficiency, Hematology, Middle Aged, 3. Good health, Nephrology, Medicine, Female, Research Article, Adult, medicine.medical_specialty, Science, Iron, Renal function, 03 medical and health sciences, Hepcidins, Hepcidin, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Internal medicine, medicine, Humans, Renal Insufficiency, Chronic, Iron Deficiency Anemia, Aged, Inflammation, Transferrin saturation, business.industry, Correction, medicine.disease, Hematopoiesis, Ferritin, Endocrinology, Iron-deficiency anemia, biology.protein, Hemoglobin, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: on behalf of the NephroTest Study Group; International audience; The metabolism of hepcidin is profoundly modified in chronic kidney disease (CKD). We investigated its relation to iron disorders, inflammation and hemoglobin (Hb) level in 199 non-dialyzed, non-transplanted patients with CKD stages 1–5. All had their glomerular filtration rate measured by 51 Cr-EDTA renal clearance (mGFR), as well as measurements of iron markers including hepcidin and of erythropoietin (EPO). Hepcidin varied from 0.2 to 193 ng/mL. The median increased from 23.3 ng/ mL [8.8–28.7] to 36.1 ng/mL [14.1–92.3] when mGFR decreased from $60 to ,15 mL/min/1.73 m 2 (p = 0.02). Patients with absolute iron deficiency (transferrin saturation (TSAT) ,20% and ferritin ,40 ng/mL) had the lowest hepcidin levels (5.0 ng/ mL [0.7–11.7]), and those with a normal iron profile (TSAT $20% and ferritin $40), the highest (34.5 ng/mL [23.7–51.6]). In multivariate analysis, absolute iron deficiency was associated with lower hepcidin values, and inflammation combined with a normal or functional iron profile with higher values, independent of other determinants of hepcidin concentration, including EPO, mGFR, and albuminemia. The hepcidin level, although it rose overall when mGFR declined, collapsed in patients with absolute iron deficiency. There was a significant interaction with iron status in the association between Hb and hepcidin. Except in absolute iron deficiency, hepcidin's negative association with Hb level indicates that it is not down-regulated in CKD anemia.
Published: 2014

42. A 3-Marker Index Improves the Identification of Iron Disorders in CKD Anaemia

Author: Lucile Mercadal, Marie Metzger, Jean Philippe Haymann, Eric Thervet, Jean-Jacques Boffa, Martin Flamant, François Vrtovsnik, Cédric Gauci, Marc Froissart, Bénédicte Stengel, NephroTest Study Group, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Université Pierre et Marie Curie - Paris 6 (UPMC), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie et Hémodialyse [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), INSERM U775, Service de Physiologie [Bichat-Claude Bernard], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), INSERM U699, Service de Néphrologie [Bichat - Claude Bernard], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Physiologie [Georges-Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service d'Urologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de recherche en épidémiologie et santé des populations ( CESP ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'urologie, néphrologie et transplantation [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Service de Physiologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ), HAL UPMC, Gestionnaire, and Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon]
Subjects: Male, Epidemiology, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, Red Cells, 030232 urology & nephrology, lcsh:Medicine, 030204 cardiovascular system & hematology, Kidney, Gastroenterology, Hemoglobins, 0302 clinical medicine, Total iron-binding capacity, Risk Factors, Chronic Kidney Disease, Clinical Epidemiology, lcsh:Science, chemistry.chemical_classification, Multidisciplinary, medicine.diagnostic_test, biology, Transferrin, Anemia, Iron deficiency, Hematology, Middle Aged, Nephrology, Medicine, Female, Research Article, Glomerular Filtration Rate, medicine.medical_specialty, Clinical Research Design, Iron, 03 medical and health sciences, Sex Factors, Hepcidin, Internal medicine, medicine, Humans, Renal Insufficiency, Chronic, Iron Deficiency Anemia, Biology, Aged, Population Biology, Transferrin saturation, business.industry, lcsh:R, medicine.disease, Ferritin, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Endocrinology, chemistry, Iron-deficiency anemia, Ferritins, biology.protein, lcsh:Q, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers
Abstract: on behalf of the NephroTest Study Group; International audience; BackgroundIron disorders are common and complex in chronic kidney disease (CKD). We sought to determine whether a 3-marker index would improve the classification of iron disorders in CKD anaemia.MethodsWe studied the association between Hb level and iron indexes combining 2 or 3 of the following markers: serum ferritin (
Published: 2014

43. An Animal Model of Type A Cystinuria Due to Spontaneous Mutation in 129S2/SvPasCrl Mice

Author: Elizabeth Thioulouse, Sophie Vandermeersch, Laurent Mesnard, Jean-Philippe Haymann, Michel Daudon, Dominique Bazin, Emmanuel Letavernier, Jean Jaubert, Marine Livrozet, Laurent Baud, Jean-Jacques Boffa, Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Physiology and Biophysics, Cornell University [New York], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique Fonctionnelle de la Souris, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Administateur, HAL Sorbonne Université
Subjects: Male, Physiology, Urology, Molecular Sequence Data, Cystine, Congenic, Mutation, Missense, lcsh:Medicine, Biology, Kidney, chemistry.chemical_compound, Kidney Calculi, Mice, Chronic Kidney Disease, medicine, Medicine and Health Sciences, Missense mutation, Animals, Kidney Stones, Amino Acid Sequence, lcsh:Science, Genetics, Renal Physiology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Multidisciplinary, Cystinuria, Point mutation, lcsh:R, Kidney metabolism, Biology and Life Sciences, Renal System, medicine.disease, Molecular biology, 3. Good health, Mice, Inbred C57BL, Disease Models, Animal, Amino Acid Transport Systems, Neutral, Phenotype, chemistry, Nephrology, Aminoaciduria, Amino Acid Transport Systems, Basic, Kidney stones, lcsh:Q, Anatomy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article
Abstract: International audience; Cystinuria is an autosomal recessive disease caused by the mutation of either SLC3A1 gene encoding for rBAT (type A cystinuria) or SLC7A9 gene encoding for b0,+AT (type B cystinuria). Here, we evidenced in a commonly used congenic 129S2/SvPasCrl mouse substrain a dramatically high frequency of kidney stones that were similar to those of patients with cystinuria. Most of 129S2/SvPasCrl exhibited pathognomonic cystine crystals in urine and an aminoaciduria profile similar to that of patients with cystinuria. In addition, we observed a heterogeneous inflammatory infiltrate and cystine tubular casts in the kidney of cystinuric mice. As compared to another classical mouse strain, C57BL/6J mice, 129S2/SvPasCrl mice had an increased mortality associated with bilateral obstructive hydronephrosis. In 129S2/SvPasCrl mice, the heavy subunit rBAT of the tetrameric transporter of dibasic amino acids was absent in proximal tubules and we identified a single pathogenic mutation in a highly conserved region of the Slc3a1 gene. This novel mouse model mimicking human disease would allow us further pathophysiological studies and may be useful to analyse the crystal/tissue interactions in cystinuria.
Published: 2014

44. Calpains contribute to vascular repair in rapidly progressive form of glomerulonephritis: potential role of their externalization

Author: Selim Aractingi, Laurent Baud, Joëlle Perez, Dany Nassar, Agnès Bellocq, Anne-Marie Faussat, Laurent Mesnard, Jean-Philippe Haymann, Lara Zafrani, Béatrice Letavernier, Emmanuelle Sachon, Charlène Levi, Emmanuel Letavernier, Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie intégrative (FRBI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de dermatologie et allergologie [CHU Tenon], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de Biologie Intégrative (IFR-BI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, Angiogenesis, Neovascularization, Physiologic, Mice, Transgenic, Mice, 03 medical and health sciences, chemistry.chemical_compound, Glomerulonephritis, 0302 clinical medicine, Cell Movement, Extracellular, Animals, Humans, Cells, Cultured, Cell Proliferation, 030304 developmental biology, Calpastatin, 0303 health sciences, biology, Calpain, [CHIM.ORGA]Chemical Sciences/Organic chemistry, Fibronectins, 3. Good health, Cell biology, Mice, Inbred C57BL, Vascular endothelial growth factor, Vascular endothelial growth factor B, Fibronectin, Endothelial stem cell, Disease Models, Animal, chemistry, 030220 oncology & carcinogenesis, Immunology, Disease Progression, biology.protein, Blood Vessels, Endothelium, Vascular, Cardiology and Cardiovascular Medicine
Abstract: Objective— Calpains, calcium-activated proteases, mediate the angiogenic signals of vascular endothelial growth factor. However, their involvement in vascular repair has not been investigated and the underlying mechanisms remain to be fully elucidated. Methods and Results— A rapidly progressive form of glomerulonephritis in wild type and transgenic mice expressing high levels of calpastatin, a calpain-specific inhibitor, was studied. Calpastatin transgene expression prevented the repair of peritubular capillaries and the recovery of renal function, limiting mouse survival. In vitro analysis detected a significant reduction of both intracellular and extracellular calpain activities in transgene expressing cells, whereas Western blotting revealed that proangiogenic factors vascular endothelial growth factor and norepinephrine increased calpain exteriorization. In vitro, extracellular calpains increased endothelial cell proliferation, migration and capillary tube formation. In vivo, delivery of nonpermeable extracellular calpastatin was sufficient to blunt angiogenesis and vascular repair. Endothelial cell response to extracellular calpains was associated with fibronectin cleavage, generating fibronectin fragments with proangiogenic capacity. In vivo, fibronectin cleavage was limited in the kidney of calpastatin transgenic mice with nephritis. Conclusion— This study demonstrates that externalized calpains participate in angiogenesis and vascular repair, partly by promoting fibronectin cleavage and thereby amplifying vascular endothelial growth factor efficiency. Thus, manipulation of calpain externalization may have therapeutic implications to control angiogenesis.
Published: 2012

45. Large Artery Stiffening and Remodeling Are Independently Associated With All-Cause Mortality and Cardiovascular Events in Chronic Kidney Disease

Author: Philippe Guardiola, Marie Metzger, Marie Briet, Stéphane Laurent, Gérard Maruani, Pascal Houillier, Jean-Philippe Haymann, Marc Froissart, Bénédicte Stengel, Pierre Boutouyrie, Alexandre Karras, Erwan Bozec, Christian Jacquot, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), SNP, Transcriptome & Epigénomique [CHU Angers] (Plateforme STE), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CIC AP-HP (hegp Ex-Broussais)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM), and Univ Angers, Okina
Subjects: Adult, Carotid Artery Diseases, Male, medicine.medical_specialty, aortic stiffness, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal function, Blood Pressure, carotid artery common, 030204 cardiovascular system & hematology, Carotid Intima-Media Thickness, 03 medical and health sciences, 0302 clinical medicine, Vascular Stiffness, Internal medicine, Internal Medicine, medicine, Humans, Cumulative incidence, Renal Insufficiency, Renal Insufficiency, Chronic, Mortality, Prospective cohort study, Pulse wave velocity, Aged, business.industry, Middle Aged, medicine.disease, Prognosis, Remodeling, [SDV] Life Sciences [q-bio], Survival Rate, Cardiovascular Diseases, Relative risk, Arterial stiffness, Cardiology, Aortic stiffness, Female, business, Kidney disease, Glomerular Filtration Rate
Abstract: Chronic kidney disease, even at moderate stages, is characterized by a high incidence of cardiovascular events. Subclinical damage to large arteries, such as increased arterial stiffness and outward remodeling, is a classical hallmark of patients with chronic kidney disease. Whether large artery stiffness and remodeling influence the occurrence of cardiovascular events and the mortality of patients with chronic kidney disease (stages 2–5) is still debated. This prospective study included 439 patients with chronic kidney disease (mean age, 59.8±14.5 years) with a mean measured glomerular filtration rate of 37 mL/min per 1.73 m 2 . Baseline aortic stiffness was estimated through carotid-femoral pulse wave velocity measurements; carotid stiffness, diameter, and intima-media thickness were measured with a high-resolution echotracking system. For the overall group of patients, the 5-year estimated survival and cumulative incidence of cardiovascular events were 87% and 16%, respectively. In regression analyses adjusted on classical cardiovascular and renal risk factors, aortic stiffness remained significantly associated with all-cause mortality (for 1 SD, Cox model–derived relative risk [95% CI], 1.48 [1.09–2.02]) and with fatal and nonfatal cardiovascular events (for 1 SD, Fine and Gray competing risks model–derived relative risk [95% CI], 1.35 [1.05–1.75]). Net reclassification improvement index was significant (29.0% [2.3–42.0%]). Carotid internal diameter was also independently associated with all-cause mortality. This study shows that increased aortic stiffness and carotid internal diameter are independent predictors of mortality in patients with stages 2 to 5 chronic kidney disease and that aortic stiffness improves the prediction of the risk.
Published: 2012

46. Spectrum of mutations in Gitelman syndrome

Author: Annabelle Venisse, Diana Kahila, Claire Rigothier, Bernard Grisart, Bruno Moulin, Marie-Christine Vantyghem, Ivan Tack, Anne-Paule Gimenez-Roqueplo, Franck Bridoux, Jean-Philippe Haymann, Olivier Devuyst, Hubert Nivet, Rosa Vargas-Poussou, Laurence Dubourg, Eva Riveira-Munoz, Anne Blanchard, Karin Dahan, Michel Godin, Pascal Houillier, Huguette Debaix, Bertrand Dussol, Robert J. Unwin, Xavier Jeunemaitre, Service de néphrologie - hémodialyse et transplantation rénale, Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Institute of Physiology, University of Zürich [Zürich] ( UZH ) -Zurich Center for Integrative Human Physiology, Klinik für Nephrologie, UniversitätsSpital, Division of Nephrology, UCL Medical School, Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), University of Zürich [Zürich] (UZH)-Zurich Center for Integrative Human Physiology, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Universität Zürich [Zürich] = University of Zurich (UZH)-Zurich Center for Integrative Human Physiology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, MESH : Molecular Sequence Data, MESH : Retrospective Studies, Receptors, Drug, Gene Dosage, 030232 urology & nephrology, MESH: Base Sequence, MESH : Child, Preschool, medicine.disease_cause, MESH: Gitelman Syndrome, MESH: Gene Dosage, MESH : Chloride Channels, 0302 clinical medicine, MESH : Child, MESH: Child, Missense mutation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Solute Carrier Family 12, Member 3, MESH : Female, MESH : Gene Dosage, Child, Gene Rearrangement, Genetics, 0303 health sciences, Mutation, MESH: Middle Aged, Symporters, MESH: Genetic Testing, MESH: Genetic Predisposition to Disease, General Medicine, Middle Aged, MESH : Adult, 3. Good health, Nephrology, MESH: Young Adult, Child, Preschool, MESH : Symporters, MESH: Solute Carrier Family 12, Member 3, MESH : Gitelman Syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Mutation, MESH : Sensitivity and Specificity, Gitelman Syndrome, Adult, MESH: Symporters, MESH: Mutation, Adolescent, MESH: Gene Rearrangement, MESH : Male, Molecular Sequence Data, Non-allelic homologous recombination, MESH : Young Adult, MESH : Solute Carrier Family 12, Member 3, Biology, Sensitivity and Specificity, Gene dosage, Young Adult, 03 medical and health sciences, Chloride Channels, MESH: Receptors, Drug, MESH : Adolescent, MESH : Genetic Testing, medicine, Humans, Genetic Predisposition to Disease, MESH : Middle Aged, Genetic Testing, Multiplex ligation-dependent probe amplification, Allele, Alleles, Retrospective Studies, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH : Receptors, Drug, MESH: Alleles, MESH: Child, Preschool, MESH: Chloride Channels, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, Gene rearrangement, MESH : Gene Rearrangement, Gitelman syndrome, medicine.disease, MESH: Male, MESH: Sensitivity and Specificity, Basic Research, MESH : Genetic Predisposition to Disease, MESH : Base Sequence, MESH : Alleles, MESH: Female
Abstract: International audience; Gitelman's syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene.
Published: 2011

47. Strong association between a new marker of hemolysis and glomerulopathy in sickle cell anemia

Author: Pierre Levy, Jean-Philippe Haymann, Katia Stankovic, Guillaume Lefèvre, François Lionnet, Jean-Pierre Perol, Robert Girot, Micheline Maier-Redelsperger, V. Avellino, Jacques Elion, Service d'oto-rhino-laryngologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie des maladies infectieuses et modélisation (ESIM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Remodelage et Reparation du Tissu Renal, Laboratoire de Génie Electrique de Grenoble (G2ELab), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Insern, UMR 763, Hôpital Robert Debré, Université Paris Diderot - Paris 7 (UPD7), Maier-Redelsperger M, Lévy P, Lionnet F, Stankovic K, Haymann JP, Lefèvre G, Avellino V, Perol JP, Girot R, Elion J., Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), and CHU Tenon [APHP]
Subjects: MESH: L-Lactate Dehydrogenase, Erythrocytes, Reticulocytes, Bilirubin, Cell Survival, Anemia, Sickle Cell, Biology, Hemolysis, 03 medical and health sciences, chemistry.chemical_compound, Hemoglobins, 0302 clinical medicine, Glomerulonephritis, Reticulocyte, Glomerulopathy, medicine, Albuminuria, Humans, Molecular Biology, MESH: Humans, L-Lactate Dehydrogenase, MESH: Erythrocytes, MESH: Biological Markers, Cell Biology, Hematology, medicine.disease, MESH: Reticulocytes, MESH: Hemolysis, Sickle cell anemia, MESH: Glomerulonephritis, 3. Good health, MESH: Albuminuria, Red blood cell, medicine.anatomical_structure, MESH: Hemoglobins, chemistry, MESH: Cell Survival, 030220 oncology & carcinogenesis, Immunology, Molecular Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Hemoglobin, medicine.symptom, MESH: Anemia, Sickle Cell, Biomarkers, 030215 immunology
Abstract: International audience; To perform a precise evaluation of the hemolytic status of patients with sickle cell anemia (SCA), advanced red blood cell parameters provided by the last generation analyzers were investigated in a series of SCA patients. The search for precise markers of hemolysis was performed to identify if patients so exposed develop organic complications related to a postulated hemolysis-linked endothelial dysfunction. Red blood cell survival was evaluated by the ratio between mature red blood cell (RBC) and reticulocyte (RET) hemoglobin (RBC-Hb/RET-Hb). In comparison with serum lactate dehydrogenase (LDH) and total bilirubin, the log (RBC-Hb/RET-Hb) was identified as the most discriminant hematological parameter to evaluate hemolysis. Furthermore, by combining this parameter with LDH, we defined a composite variable, which we called CVar, that is highly correlated with albuminuria and might constitute a powerful new marker of risk for this complication.
Published: 2010

48. Cellules souches et réparation tubulaire après ischémie rénale

Author: Laurent Baud, Jean-Philippe Haymann, Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Maylin, Françoise
Subjects: Pathology, medicine.medical_specialty, Urinary system, 030232 urology & nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, medicine, 030304 developmental biology, 0303 health sciences, Kidney, MESH: Kidney Diseases, MESH: Humans, Renal ischemia, Vascular disease, business.industry, MESH: Kidney Failure, Acute, General Medicine, MESH: Kidney, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Epithelium, medicine.anatomical_structure, Stem cell, MESH: Ischemia, MESH: Stem Cell Transplantation, business, Kidney disease
Published: 2005

49. Le rein profond dans la physiopathologie des lésions rénales : rôle des structures médullaires, des capillaires péritubulaires et de l'urothélium

Author: Tabibzadeh, Nathalie, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université, and Jean-Philippe Haymann
Subjects: Physiopathologie rénale, Microvascularization, Maladie rénale chronique, Urothélium, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Kidney medulla, Hyposthenuria, Médulla rénale, Hyposthénurie, Microvascularisation
Abstract: Le rein profond correspond aux structures médullaires, vasculaires post-glomérulaires, et à l’urothélium intrarénal. Cette définition regroupe des acteurs de la physiologie rénale dont l’étude est parfois difficile du fait de leur localisation. La fonction de concentration en particulier se rattache directement à ces structures profondes. L’objet de l’étude est donc une approche physiopathologique des altérations du rein profond, qu’elles soient à l’origine de la pathologie rénale, ou qu’elles en soient le reflet. La première partie du travail repose sur des données épidémiologiques de patients atteints d’une maladie rénale chronique et montre que la diminution de l’osmolalité urinaire à jeun est prédictive d’une dégradation du débit de filtration glomérulaire et d’une insuffisance rénale terminale chez ces patients. La deuxième étude porte sur le rôle des capillaires péritubulaires d’une part dans l’hémodynamique rénale, d’autre part dans l’apparition des lésions tubulaires. Dans un modèle d’hypertension artérielle, le rôle des capillaires péritubulaires dans la toxicité rénale de l’hème y est précisé. Enfin, la troisième partie concerne la structure la plus profonde du rein, l’urothélium intrarénal. Des données de la littérature laissant entrevoir son rôle potentiel dans les fonctions rénales, un modèle murin transgénique d’ablation conditionnelle de l’urothélium a été mis au point. L’osmolalité urinaire était diminuée et l’urée et la créatininémie étaient augmentées après ablation des cellules urothéliales. Ces résultats suggèrent un rôle de l’urothélium intrarénal dans la fonction de concentration des urines ; son rôle en physiopathologie doit encore être précisé.; Le rein profond correspond aux structures médullaires, vasculaires post-glomérulaires, et à l’urothélium intrarénal. Cette définition regroupe des acteurs de la physiologie rénale dont l’étude est parfois difficile du fait de leur localisation. La fonction de concentration en particulier se rattache directement à ces structures profondes. L’objet de l’étude est donc une approche physiopathologique des altérations du rein profond, qu’elles soient à l’origine de la pathologie rénale, ou qu’elles en soient le reflet. La première partie du travail repose sur des données épidémiologiques de patients atteints d’une maladie rénale chronique et montre que la diminution de l’osmolalité urinaire à jeun est prédictive d’une dégradation du débit de filtration glomérulaire et d’une insuffisance rénale terminale chez ces patients. La deuxième étude porte sur le rôle des capillaires péritubulaires d’une part dans l’hémodynamique rénale, d’autre part dans l’apparition des lésions tubulaires. Dans un modèle d’hypertension artérielle, le rôle des capillaires péritubulaires dans la toxicité rénale de l’hème y est précisé. Enfin, la troisième partie concerne la structure la plus profonde du rein, l’urothélium intrarénal. Des données de la littérature laissant entrevoir son rôle potentiel dans les fonctions rénales, un modèle murin transgénique d’ablation conditionnelle de l’urothélium a été mis au point. L’osmolalité urinaire était diminuée et l’urée et la créatininémie étaient augmentées après ablation des cellules urothéliales. Ces résultats suggèrent un rôle de l’urothélium intrarénal dans la fonction de concentration des urines ; son rôle en physiopathologie doit encore être précisé.
Published: 2018

50. Troubles hydro-électrolytiques associes a la néphropathie drépanocytaire : le cas particulier des phosphates

Author: Savenkoff, Benjamin, Université de Lorraine (UL), Université de Lorraine, and Jean-Philippe Haymann
Subjects: [SDV]Life Sciences [q-bio], Thèse d'exercice de médecine, Non disponible / Not available
Abstract: La drépanocytose homozygote est une maladie héréditaire fréquente. La néphropathie drépanocytaire est une des complications chroniques les plus fréquentes de cette maladie qui touche 50 à 80% des patients adultes. Les atteintes histologiques concernent à la fois les glomérules expliquant la forte prévalence d’une protéinurie mais aussi les vasa recta médullaires, à l’origine d’une néphropathie tubulo-interstitielle. Divers troubles hydroélectrolytiques sont associés à cette néphropathie. Les troubles de concentration des urines liés à un défaut de gradient osmotique cortico-papillaire sont les plus décrits et sont responsables d’un syndrome polyuropolydipsique. Des troubles de l’acidification urinaire à l’origine d’une acidose métabolique sont également décrits et seraient liés à un défaut du gradient d’ammonium cortico-papillaire. Les atteintes des fonctions proximales du tubule rénal sont moins bien connues. Il semble exister un hyperfonctionnement primitif du tube proximal avec notamment une hyper-réabsorption des phosphates responsable d’une hyperphosphatémie. Nous avons étudié la prévalence de l’hyperphosphatémie sur une cohorte de 429 patients drépanocytaires homozygotes adultes et ses déterminants dans un sous-groupe de 75 patients (non insuffisants rénaux) ayant bénéficiés d’une exploration du métabolisme phospho-calcique au cours d’un hôpitalde jour dans le Service d’Explorations Fonctionnelles de l’hôpital Tenon. La prévalence observée de l’hyperphosphatémie dans la population générale est de 12.8 % et de 42% dans le sous-groupe adressé pour le bilan d’une néphropathie (hyperfiltration et/ou albuminurie). Nos résultats confirment une nette augmentation du taux de réabsorption des phosphates, qui semble indépendant des principales hormones connues pour être impliquées dans ce mécanisme telles la PTH, Klotho, ou la GH avec une concentrationplasmatique du FGF-23 très élevée qui suggère une contre-régulation adaptée à l’hyperphosphatémie. Cette augmentation de la réabsorption tubulaire proximale concerne également d’autres solutés notamment l’acide urique et les SDMA. L’association de l’hyperphosphatémie avec une augmentation des SDMA, de l’albuminurie, de la vitesse de régurgitation tricuspide (évaluant une hypertension artérielle pulmonaire) et des antécédents de vasculopathie cérébrale suggère que cette anomalie hydro-électrolytique pourrait représenter un facteur de risque cardio-vasculaire dans cette population à l’instar d’autres populations comme les patients dialysés. Dans cette perspective, une étude interventionnelle par chélateurs des phosphates visant à normaliser la phosphatémie seraient intéressante à mener afin d’évaluer un effet potentiellement bénéfique sur le coeur,les vaisseaux et les reins
Published: 2015

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