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1. Markers of graft microvascular endothelial injury may identify harmful donor-specific anti-HLA antibodies and predict kidney allograft loss

Author

Alexandre Hertig, Matthieu Jamme, Jean-Luc Taupin, Nacera Ouali, Eric Rondeau, Isabelle Brocheriou, Yi-Chun Xu-Dubois, Marie Audouin, Chantal Jouanneau, Yosu Luque, David Buob, and Kevin Louis

Subjects
Graft Rejection, Male, Pathology, Biopsy, Vimentin, 030230 surgery, Kidney, 0302 clinical medicine, HLA Antigens, Immunology and Allergy, Pharmacology (medical), Renal Insufficiency, biology, medicine.diagnostic_test, Histocompatibility Testing, Microfilament Proteins, Middle Aged, Allografts, Tissue Donors, medicine.anatomical_structure, Immunohistochemistry, Female, Antibody, Adult, Reoperation, medicine.medical_specialty, Human leukocyte antigen, Antibodies, Endothelial activation, 03 medical and health sciences, Complement C4b, medicine, Humans, HSP47 Heat-Shock Proteins, Aged, Antilymphocyte Serum, Retrospective Studies, Fascin, Transplantation, business.industry, Microcirculation, Kidney Transplantation, Peptide Fragments, body regions, biology.protein, Endothelium, Vascular, Carrier Proteins, business, Biomarkers, Follow-Up Studies
Abstract

Graft microvasculature is a major target of donor-specific antibodies (DSA) and endothelial damage is direct evidence of antibody-mediated rejection (ABMR). Using immunohistochemistry, we analyzed the expression of three microvascular endothelial activation markers (fascin, vimentin, and hsp47), suggestive of endothelial-to-mesenchymal transition (EndMT) in 351 graft biopsies from 248 kidney recipients, with concomitant screening of circulating antihuman leukocyte antigen (HLA) DSA at the time of the biopsy. The factors associated with EndMT marker expression were DSA and the presence of microvascular inflammation (MI). EndMT expressing grafts had significantly more allograft loss compared to EndMT negative grafts (P < .0001). The expression of EndMT markers positively correlated with anti-HLA DSA class II mean fluorescence intensity (MFI) levels and especially identified DQ and DR antibodies as being more closely associated with microvascular injury. Moreover, only DSA linked to positive EndMT score affected allograft survival, regardless of DSA MFI levels or presence of C4d deposition. Thus, EndMT markers could represent a clinically relevant tool for early identification of ongoing endothelial injury, harmful DSA, and patients at high risk for allograft failure.

Published
2019
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2. Chemical composition and distribution of tattoo inks within tattoo‐associated keratoacanthoma

Author

Chantal Jouanneau, Ivan T. Lucas, R. Amode, Nicolas Kluger, Dominique Bazin, L. Deschamps, Hester Colboc, Philippe Moguelet, S. Reguer, Vincent Descamps, Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Wound Healing Department, Rothschild Hospital, Sorbonne Université (SU), Laboratoire Cellule Planing (LCP), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Synchrotron Soleil, DiffAbs beamline, Saint-Aubin, BP 48, 91192 Gif-sur-Yvette Cedex, France (SYNCHROTRON SOLEIL, DIFFABS BEAMLINE, SAINT-AUBIN, BP 48, 91192 GIF-SUR-YVETTE CEDEX, FRANCE), Synchrotron Soleil, DiffAbs beamline, Saint-Aubin, BP 48, 91192 Gif-sur-Yvette Cedex, France, AP-HP - Hôpital Bichat - Claude Bernard [Paris], 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), Laboratoire Interfaces et Systèmes Electrochimiques (LISE), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Département de Génétique [AP-HP Hôpital Bichat] (Hôpitaux Universitaires Paris Nord Val de Seine - HUPNVS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Nord Val de Seine (HUPNVS), Helsinki University Hospital [Helsinki, Finlande], University of Helsinki, CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Maladies rénales fréquentes et rares : des mécanismes moléculaires à la médecine personnalisée (CoRaKID), and Helsingin yliopisto = Helsingfors universitet = University of Helsinki

Subjects
Keratoacanthoma, medicine.medical_specialty, 02 engineering and technology, Dermatology, azo pigment, tattooing, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Humans, [CHIM]Chemical Sciences, Medicine, Coloring Agents, Ultraviolet radiation, business.industry, 021001 nanoscience & nanotechnology, medicine.disease, synchroton radiation techniques, 3. Good health, body regions, Infectious Diseases, Multiple factors, Raman spectroscopy, Ink, 0210 nano-technology, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, circulatory and respiratory physiology
Abstract

International audience; Carcinogenic risk of tattoo inks remains unclear, and their composition is poorly regulated. Various types of carcinogenic compounds can be found in tattoo inks, including primary aromatic amines (PAA), cleavage products of organic azo colourants, found in coloured inks.1 Many cases of skin cancers occurring within tattoos have been reported, including cases of keratoacanthoma (KA) developed on red ink.2 Pathogenesis of KA on tattoos remains unclear and is probably due to multiple factors: trauma induced by the needle during the tattoo itself, inflammatory reactions, ultraviolet radiation, direct carcinogenicity of the tattoo inks and individual background

Published
2020
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3. Physicochemical characterization of inorganic deposits associated with granulomas in cutaneous sarcoidosis

Author

Michel Daudon, Dominique Bazin, Hester Colboc, Chantal Jouanneau, Vincent Frochot, J.-F. Bernaudin, Claude Bachmeyer, Philippe Moguelet, Emmanuel Letavernier, Raphael Weil, Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service d’Anatomie et cytologie pathologiques [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), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (LCMCP-SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Service de Médecine Interne [CHU Tenon], 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), Service de pneumologie [Avicenne], Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et cytologie pathologiques [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), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], and Gestionnaire, Hal Sorbonne Université

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Granuloma formation, Chemical Phenomena, Sarcoidosis, Cutaneous Sarcoidosis, Dermatology, Skin Diseases, Calcium Carbonate, 030207 dermatology & venereal diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Spectroscopy, Fourier Transform Infrared, Medicine, Humans, Inorganic particles, Combined method, Aged, Skin, Granuloma, business.industry, Field emission scanning electron microscopy, Spectrometry, X-Ray Emission, Mean age, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, Middle Aged, medicine.disease, Silicon Dioxide, 3. Good health, Infectious Diseases, 030228 respiratory system, Inorganic Chemicals, Microscopy, Electron, Scanning, Female, Microscopy, Polarization, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract

International audience; BACKGROUND: Sarcoidosis, characterized by epithelioid granulomas, is considered to be caused by a complex interplay between genetics and environmental agents. It has been hypothesized that exogenous inorganic particles as crystalline silica could be a causal or adjuvant agent in sarcoidosis onset.OBJECTIVES: To investigate the location, frequency and physicochemical characteristics of foreign materials and mineral tissue deposits in the granulomatous area of cutaneous sarcoidosis.METHODS: Skin biopsies (n = 14) from patients diagnosed with cutaneous sarcoidosis (mean age 43 years; 11 patients with extracutaneous involvement) were investigated using polarized light examination (PLE), μFourier Transform Infra-Red (μFT-IR) spectroscopy and Field Emission Scanning Electron Microscopy coupled with Energy Dispersive X-ray Spectroscopy (FE-SEM/EDX).RESULTS: Combined PLE, μFT-IR, FE-SEM/EDX analysis allowed to characterize mineral deposits in 7/14 biopsies (50%). It identified crystalline silica (SiO2 ) inside granulomas in three biopsies and calcite (CaCO3 ) at their periphery in 4.CONCLUSION: This study emphasizes the need of using combined methods for assessment of mineral deposits in granulomatous diseases. According to the location and characteristics of deposits, we can hypothesize that SiO2 particles contribute to the granuloma formation, whereas CaCO3 deposits are related to the granuloma biology. However, the significance of the association between SiO2 deposits and sarcoidosis is still disputed.

Published
2019
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4. Flyscan opportunities in medicine: the case of quantum rattle based on gold quantum dots

Author

Julien Berthault, Chantal Jouanneau, Dominique Thiaudière, Corinne Chanéac, Nicolas Leclercq, Jean-François Greisch, Emmanuel Esteve, Bernard Leyh, Dominique Bazin, Solenn Reguer, Pierre Ronco, Michel Daudon, Cédric Boissière, Cristian Mocuta, Gustavo Lugo, 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), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Synchrotron SOLEIL (SSOLEIL), Centre National de la Recherche Scientifique (CNRS), Matériaux Hybrides et Nanomatériaux (LCMCP-MHN), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Chemistry [Liège], Université de Liège, Institute of Nanotechnology [Karlsruhe] (INT), Karlsruhe Institute of Technology (KIT), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (LCMCP-SMiLES), Matériaux Hybrides et Procédés (LCMCP-MHP ), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Nuclear and High Energy Physics, Materials science, X-ray fluorescence, Nanotechnology, 02 engineering and technology, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, 010402 general chemistry, 01 natural sciences, law.invention, Data acquisition, law, gold-cluster-enriched mesoporous silica nanospheres, Absorption (electromagnetic radiation), xanes, Instrumentation, Quantum, Radiation, business.industry, [CHIM.MATE]Chemical Sciences/Material chemistry, Mesoporous silica, 021001 nanoscience & nanotechnology, [SDE.ES]Environmental Sciences/Environmental and Society, Synchrotron, Flyscan method, 0104 chemical sciences, 3. Good health, Beamline, Quantum dot, Optoelectronics, 0210 nano-technology, business, theranostic vectors
Abstract

International audience; The new rapid scan method, Flyscan mode, implemented on the DiffAbs beamline at Synchrotron SOLEIL, allows fast micro-X-ray fluorescence data acquisition. It paves the way for applications in the biomedical field where a large amount of data is needed to generate meaningful information for the clinician. This study presents a complete set of data acquired after injection of gold-cluster-enriched mesoporous silica nanospheres, used as potential theranostic vectors, into rats. While classical X-ray fluorescence investigations (using step-by-step acquisitions) are based on a limited number of samples (approximately one per day at the DiffAbs beamline), the Flyscan mode has enabled gathering information on the interaction of nanometer-scale vectors in different organs such as liver, spleen and kidney at the micrometer scale, for five rats, in only a single five-day synchrotron shift. Moreover, numerous X-ray absorption near-edge structure spectra, which are beam-time-consuming taking into account the low concentration of these theranostic vectors, were collected

Published
2017
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5. Vancomycin-Associated Cast Nephropathy

Author

Sophie Vandermeersch, Dominique Bazin, Yosu Luque, Vincent Frochot, Sandrine Placier, Alice Wolfromm, Clément Gosset, Emmanuel Esteve, Chantal Jouanneau, Emmanuel Letavernier, Perrine Frere, Michel Daudon, Kevin Louis, Laurent Mesnard, Marie-Christine Verpont, Maren Burbach, Anna Boueilh, Eric Rondeau, Dominique Langui, CHU Tenon [AP-HP], 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), Service d'immuno-hématologie pédiatrique [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), Service d'Anatomie pathologique [CHU Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de Néphrologie-Transplantation [CHU Saint-Louis], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), HAL-UPMC, Gestionnaire, 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), Service d'Explorations fonctionnelles multidisciplinaires [CHU Tenon], 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), 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), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP]

Subjects
Pathology, medicine.medical_specialty, Tamm–Horsfall protein, medicine.drug_class, Antibiotics, 030232 urology & nephrology, Kidney, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Nephropathy, Nephrotoxicity, 03 medical and health sciences, 0302 clinical medicine, Vancomycin, Hypovolemia, medicine, Humans, 030212 general & internal medicine, Acute tubular necrosis, biology, medicine.diagnostic_test, business.industry, General Medicine, biochemical phenomena, metabolism, and nutrition, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, Nephrology, biology.protein, Kidney Diseases, Renal biopsy, medicine.symptom, Brief Communications, business, medicine.drug
Abstract

International audience; Vancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient’s renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different in vivo imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury.

Published
2017
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6. 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
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7. FP731MARKERS OF MICRO-VASCULAR ENDOTHELIAL CELL ACTIVATION IDENTIFY POOR RENAL GRAFT OUTCOME IN EARLY BIOPSY WITH ACUTE TUBULAR NECROSIS

Author

Benoit Barrou, Philippe Rouvier, Nadia Arzouk Snanoudj, Alexandre Hertig, Jean-Luc Taupin, Eric Rondeau, Chantal Jouanneau, Yi-Chun Xu-Dubois, David Buob, Kevin Louis, Pedram Ahmadpoor, Pierre Galichon, Isabelle Brocheriou, and Anthony Corchia

Subjects
Endothelial stem cell, Transplantation, Pathology, medicine.medical_specialty, medicine.diagnostic_test, Nephrology, business.industry, Biopsy, Renal graft, Medicine, business, medicine.disease, Acute tubular necrosis
Published
2018
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8. Markers of Endothelial-to-Mesenchymal Transition: Evidence for Antibody-Endothelium Interaction during Antibody-Mediated Rejection in Kidney Recipients

Author

Isabelle Brocheriou, Nacera Ouali, Shannon R. Reese, Nuala Mooney, Pierre Levy, Yi-Chun Xu-Dubois, Arjang Djamali, Julie Peltier, Zela Keuylian, Julien Lion, Chantal Jouanneau, Alexandre Hertig, Eric Rondeau, and Caroline Suberbielle-Boissel

Subjects
Graft Rejection, Male, Pathology, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Endothelium, 030232 urology & nephrology, Vimentin, 030230 surgery, Peritubular capillaries, Antibodies, Endothelial activation, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Transplantation Immunology, Biopsy, medicine, Humans, Heat shock protein 47, Retrospective Studies, Kidney, medicine.diagnostic_test, biology, business.industry, General Medicine, Middle Aged, Capillaritis, medicine.disease, Kidney Transplantation, medicine.anatomical_structure, Nephrology, biology.protein, Female, Endothelium, Vascular, business, Biomarkers
Abstract

Antibody-mediated rejection (ABMR) is a leading cause of allograft loss. Treatment efficacy depends on accurate diagnosis at an early stage. However, sensitive and reliable markers of antibody-endothelium interaction during ABMR are not available for routine use. Using immunohistochemistry, we retrospectively studied the diagnostic value of three markers of endothelial-to-mesenchymal transition (EndMT), fascin1, vimentin, and heat shock protein 47, for ABMR in 53 renal transplant biopsy specimens, including 20 ABMR specimens, 24 cell-mediated rejection specimens, and nine normal grafts. We validated our results in an independent set of 74 unselected biopsy specimens. Endothelial cells of the peritubular capillaries in grafts with ABMR expressed fascin1, vimentin, and heat shock protein 47 strongly, whereas those from normal renal grafts did not. The level of EndMT marker expression was significantly associated with current ABMR criteria, including capillaritis, glomerulitis, peritubular capillary C4d deposition, and donor-specific antibodies. These markers allowed us to identify C4d-negative ABMR and to predict late occurrence of disease. EndMT markers were more specific than capillaritis for the diagnosis and prognosis of ABMR and predicted late (up to 4 years after biopsy) renal graft dysfunction and proteinuria. In the independent set of 74 renal graft biopsy specimens, the EndMT markers for the diagnosis of ABMR had a sensitivity of 100% and a specificity of 85%. Fascin1 expression in peritubular capillaries was also induced in a rat model of ABMR. In conclusion, EndMT markers are a sensitive and reliable diagnostic tool for detecting endothelial activation during ABMR and predicting late loss of allograft function.

Published
2015

9. Spectrum and Prognosis of Noninfectious Renal Mixed Cryoglobulinemic GN

Author

Mohamad, Zaidan, Benjamin, Terrier, Agnieszka, Pozdzik, Thierry, Frouget, Nathalie, Rioux-Leclercq, Christian, Combe, Sébastien, Lepreux, Aurélie, Hummel, Laure-Hélène, Noël, Isabelle, Marie, Bruno, Legallicier, Arnaud, François, Antoine, Huart, David, Launay, Gilles, Kaplanski, Frank, Bridoux, Philippe, Vanhille, Raifah, Makdassi, Jean-François, Augusto, Philippe, Rouvier, Alexandre, Karras, Chantal, Jouanneau, Marie-Christine, Verpont, Patrice, Callard, Fabrice, Carrat, Olivier, Hermine, Jean-Marc, Léger, Xavier, Mariette, Patricia, Senet, David, Saadoun, Pierre, Ronco, Isabelle, Brochériou, Patrice, Cacoub, Emmanuelle, Plaisier, Thierry, Zénone, CHU Necker - Enfants Malades [AP-HP], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [APHP], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Department of Nephrology - Dialysis and Renal Transplantation, Hôpital Erasmes, Laboratory of Experimental Nephrology - Department of Biochimie, Université Libre de Bruxelles [Bruxelles] (ULB), Service de néphrologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Néphrologie-transplantation-dialyse [Bordeaux], CHU Bordeaux [Bordeaux], Centre de compétences des microangiopathies thrombotiques, Université Bordeaux Segalen - Bordeaux 2, Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de Médecine Interne [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service d'Anatomie et Cytologie Pathologique [Rouen], Service de Néphrologie et Immunopathologie Clinique, Centre Hospitalier Universitaire de Toulouse, PRES Université de Toulouse, Laboratoire d'Immunologie (EA 2686), Université de Lille, Droit et Santé, Inflammation: mécanismes et régulation et interactions avec la nutrition et les candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Service de Médecine Interne et d'Immunologie clinique, Centre National de Référence Maladies rares-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de néphrologie - hémodialyse et transplantation rénale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de médecine interne et néphrologie, CH Valenciennes, Université d'Angers - Faculté de médecine (UA UFR Médecine), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Université d'Angers (UA), 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), 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 [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), CHU Saint-Antoine [APHP], Centre de référence des mastocytoses, Service d'Hématologie Adulte, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Régulation de la réponse immune, infection VIH-1 et autoimmunité, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Immunologie - Immunopathologie - Immunothérapie (I3), 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 d'immunologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Sorbonne Universités, Service de Néphrologie et Dialyses [CHU Tenon], Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] ( DHU - I2B ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université Libre de Bruxelles [Bruxelles] ( ULB ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Laboratoire d'Immunologie ( EA 2686 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lille, Droit et Santé, Centre National de Référence Maladies rares-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -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, Université d'Angers - Faculté de médecine ( UA UFR Médecine ), Université d'Angers ( UA ) -CHU Angers, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Institut Pierre Louis d'Epidémiologie et de Santé Publique ( iPLESP ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Département de santé publique, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre d'Immunologie et de Maladies Infectieuses ( CIMI ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie - Immunopathologie - Immunothérapie ( I3 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Anatomopathologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Université libre de Bruxelles (ULB), Service de néphrologie [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Médecine Interne [CHU Rouen], Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), 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), CHU Tenon [AP-HP], CHU Saint-Antoine [AP-HP], Centre de référence des mastocytoses (CEREMAST), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie et allergologie [CHU Tenon], Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service Médecine interne et immunopathologie clinique [CHU Toulouse], Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pitié-Salpêtrière [APHP]-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université de Lille, Droit et Santé-Institut National de la Santé et de la Recherche Médicale (INSERM), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)

Subjects
Male, medicine.medical_specialty, Pathology, Cyclophosphamide, Glomerulonephritis, Membranoproliferative, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Lymphoproliferative disorders, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Clinical Research, Internal medicine, medicine, Humans, Cause of death, Retrospective Studies, 030203 arthritis & rheumatology, Proteinuria, [ SDV ] Life Sciences [q-bio], business.industry, General Medicine, membranoproliferative GN, Middle Aged, medicine.disease, Prognosis, Cryoglobulinemia, 3. Good health, Lymphoma, Regimen, Nephrology, histopathology, Rituximab, Female, medicine.symptom, business, Immunosuppressive Agents, medicine.drug
Abstract

International audience; Noninfectious mixed cryoglobulinemic GN (MCGN) has been poorly investigated. We analyzed presentation and outcome of 80 patients with biopsy-proven MCGN, which were identified in the retrospective French CryoVas survey. MCGN was related to primary Sjögren's syndrome in 22.5% of patients and to lymphoproliferative disorders in 28.7% of patients, and was defined as essential in 48.8% of patients. At presentation, hematuria, proteinuria ≥1 g/d, hypertension, and renal failure were observed in 97.4%, 84.8%, 85.3%, and 82.3% of cases, respectively. Mean±eGFR was 39.5±20.4 ml/min per 1.73 m2. Membranoproliferative GN was the predominant histologic pattern, observed in 89.6% of cases. Renal interstitium inflammatory infiltrates were observed in 50% of cases. First-line treatment consisted of steroids alone (27.6%) or in association with rituximab (21.1%), alkylating agents (36.8%) or a combination of cyclophosphamide and rituximab (10.5%). After a mean follow-up of 49.9±45.5 months, 42.7% of patients relapsed with a renal flare in 75% of cases. At last follow-up, mean eGFR was 50.2±26.1 ml/min per 1.73 m2 with 9% of patients having reached ESRD; 59% and 50% of patients achieved complete clinical and renal remission, respectively. A rituximab+steroids regimen prevented relapses more effectively than steroids alone or a cyclophosphamide+steroids combination did, but was associated with a higher rate of early death when used as first-line therapy. Severe infections and new-onset B-cell lymphoma occurred in 29.1% and 8.9% of cases, respectively; 24% of patients died. In conclusion, noninfectious MCGN has a poor long-term outcome with severe infections as the main cause of death

Published
2015
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10. Risk Factors for Early Epithelial to Mesenchymal Transition in Renal Grafts

Author

P. Sebe, Alexandre Hertig, Denis Glotz, Chantal Jouanneau, Nacera Ouali, Jérôme Verine, Eric Rondeau, Pierre-Yves Ancel, Yi-Chun Xu-Dubois, and Béatrice Mougenot

Subjects
Adult, Graft Rejection, Male, Pathology, medicine.medical_specialty, Biopsy, Vimentin, Nephropathy, Mesoderm, Risk Factors, Chronic allograft nephropathy, Cadaver, medicine, Renal fibrosis, Humans, Immunology and Allergy, Pharmacology (medical), Epithelial–mesenchymal transition, Transplantation, Kidney, biology, business.industry, Epithelial Cells, Middle Aged, medicine.disease, Immunohistochemistry, Kidney Transplantation, Tissue Donors, medicine.anatomical_structure, embryonic structures, biology.protein, Female, business, Kidney disease
Abstract

Epithelial-to-mesenchymal transition (EMT) of tubular epithelial cells (TECs) may participate in the pathogenesis of renal fibrosis. We performed a prospective study of EMT markers in protocol biopsies obtained 3 months after engraftment from 56 patients who received deceased donor kidneys and who had stable renal function. The presence of EMT was examined, and quantified by immunohistochemical staining for vimentin and translocation of beta-catenin to the cytoplasm. EMT status was defined as the presence of EMT markers inor = 10% of TECs. EMT features were virtually absent in implantation biopsies, whereas 41% of the grafts were EMT-positive in the absence of advanced chronic allograft nephropathy. Thirteen patients (23%) had borderline changes or acute rejection. EMT features were more frequent in these patients than in those with normal kidney grafts (vimentin expression, p = 0.003; beta-catenin translocation, p = 0.002). EMT in grafts corresponded with elevated serum creatinine of the donor before the recovery of kidney (p = 0.02) and longer cold ischemia time (p = 0.02). In contrast, the donor age had no influence on the expression of EMT markers. These results suggest that EMT is an early and frequent phenomenon in kidney transplants that could be triggered by immunological and/or ischemic tubular injury.

Published
2006
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11. Long-Term Renal Effects of Low-Dose Cyclosporine in Uveitis-Treated Patients

Author

Gilbert Deray, Alain Mallet, Philippe Maksud, Chantal Jouanneau, Marie Chantal Jaudon, Corinne Isnard Bagnis, Phuc LeHoang, Sophie Tezenas du Montcel, and Hélène Beaufils

Subjects
Adult, Male, medicine.medical_specialty, Side effect, Urology, Renal function, Kidney, Drug Administration Schedule, Nephrotoxicity, Cohort Studies, Uveitis, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Dose-Response Relationship, Drug, business.industry, General Medicine, Effective renal plasma flow, Middle Aged, medicine.disease, Fibrosis, Kidney Tubules, Endocrinology, medicine.anatomical_structure, Nephrology, Creatinine, Hypertension, Cyclosporine, Trough level, Female, Atrophy, business, Immunosuppressive Agents, Follow-Up Studies, Glomerular Filtration Rate, Kidney disease
Abstract

Cyclosporine (CsA), a widely used immunosuppressive drug, is an effective treatment of sight-threatening posterior idiopathic uveitis. CsA's main side effect is nephrotoxicity. The aim of this single-center prospective cohort study (conducted in a tertiary care teaching hospital in Paris, France) was to assess the long-term renal tolerance of a low-dose CsA treatment in patients with previously healthy kidneys on clinical, biologic, and pathologic criteria. Forty-one patients treated with 4.3 +/- 1.6 mg/kg body wt per day CsA for 44.9 +/- 3.6 mo were included. Mean follow-up was 55.4 +/- 0.2 mo. BP, CsA trough level, and renal function were prospectively monitored together with blood urea, creatinine clearance, GFR, and effective renal plasma flow. Eleven patients underwent serial kidney biopsies before and after 2 yr of a 4 +/- 0.9 mg/kg daily CsA treatment. Sustained low-dose CsA treatment induced a significant increase in plasma creatinine (P < 0.0001), a significant decrease in creatinine clearance (P < 0.0001), and isotopic GFR (P < 0.0001) over time. The highest dose induced more severe alterations in any of the renal parameters than the lowest dose. Prevalence of hypertension was particularly high. Histopathologic data showed significant interstitial fibrosis (P < 0.003) and tubular atrophy (P < 0.003) after 2 yr. Low-dose long-term CsA treatment induces significant renal impairment and a high incidence of hypertension. Our study suggests that lowering daily dosage may prevent CsA-induced nephrotoxicity if a daily dose of < or =3 mg/kg is used. Whether once established it is reversible is still prospective, although the occurrence of interstitial fibrosis in the kidney would argue against reversibility.

Published
2002
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12. Expression of the transcriptional regulator snail1 in kidney transplants displaying epithelial-to-mesenchymal transition features

Author

Yi-Chun Xu-Dubois, Pierre Galichon, Nacera Ouali, Alexandre Hertig, Chantal Jouanneau, Eric Rondeau, Romain Morichon, Isabelle Brocheriou, Edith Baugey, 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), Université Pierre et Marie Curie - Paris 6 (UPMC), 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), Remodelage et Reparation du Tissu Renal, Service de néphrologie [Rennes], CHU Pontchaillou [Rennes]-Hôpital Pontchaillou-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Cytométrie et Imagerie Saint-Antoine (CISA), Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes]

Subjects
Graft Rejection, Male, Pathology, medicine.medical_specialty, Epithelial-Mesenchymal Transition, Biopsy, Vimentin, Smad2 Protein, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Peritubular capillaries, Fibrosis, medicine, Humans, Epithelial–mesenchymal transition, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Transplantation, Kidney, medicine.diagnostic_test, biology, business.industry, Epithelial Cells, Middle Aged, medicine.disease, Immunohistochemistry, Kidney Transplantation, medicine.anatomical_structure, Kidney Tubules, Nephrology, biology.protein, Kidney Failure, Chronic, Female, business
Abstract

Background. The epithelial response to injury is stereotypical and reminiscent of epithelial-to-mesenchymal transitions (EMTs), such as those observed during embryogenesis and tumour metastasis. In the context of solid organ transplantation, EMT-like features are often acquired by epithelial cells and are predictive of graft fibrosis. Here, we studied the possible involvement of several major transcriptional regulators, including snail1, phospho-Smad 2/3 and zeb1, in EMT induction in human renal grafts. Methods. We used immunohistochemistry to detect the presence of these EMT transcriptional regulators along with that of two validated EMT markers (intra-cytoplasmic translocation of β-catenin, de novo expression of vimentin), in 103 renal graft biopsy samples taken for routine surveillance or for a clinical indication. Results. We observed the nuclear accumulation of snail1 and phospho-smad2/3 in tubular cells displaying EMT. The level of snail1 was significantly correlated with the scores of EMT markers (β-catenin: ρ= 0.94, P < 0.0001; vimentin: ρ= 0.93, P < 0.0001) and with deteriorated graft function and proteinuria at the time of biopsy. Furthermore, intense staining for both snail1 and vimentin in tubular cells (≥10% of tubules) was predictive of graft dysfunction 21 months post-biopsy, independently of the other known risk factor for long-term graft dysfunction. In contrast, in both normal and diseased graft, zeb1 expression was detected exclusively in the endothelial cells of glomeruli and peritubular capillaries. Conclusion. This study suggests that snail1 is closely related to the fibrogenic, EMT-like response of the tubular epithelium in human renal grafts and predictive of graft function loss.

Published
2014
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13. Erythropoietin enhances recovery after cisplatin‐induced acute renal failure in the rat

Author

Corinne Isnard Bagnis, Claude Jacobs, Gilbert Deray, Claude Jacquiaud, Hélène Beaufils, Marie Chantal Jaudon, Chantal Jouanneau, Yvette Adabra, Gilles Le Nahour, and Richard Bourbouze

Subjects
Male, medicine.medical_specialty, medicine.medical_treatment, Intraperitoneal injection, Renal function, Antineoplastic Agents, Urine, Kidney, Rats, Sprague-Dawley, Internal medicine, medicine, Animals, Erythropoietin, Cisplatin, Transplantation, Chemotherapy, business.industry, Acute Kidney Injury, medicine.disease, Diuresis, Rats, medicine.anatomical_structure, Endocrinology, Nephrology, Renal blood flow, business, Glomerular Filtration Rate, Kidney disease, medicine.drug
Abstract

Background Erythropoietin (Epo) is a growth factor whose synthesis mainly takes place in the kidney. Epo has been shown to support the growth not only of erythroid progenitor cells but also of certain other cell types. We attempted to establish whether Epo enhances the recovery from acute renal failure induced by cisplatin. Methods Sprague-Dawley rats were randomized into three groups. In the cisplatin group, animals received one intraperitoneal injection of cisplatin (6 mg/kg) and a daily injection of placebo for 9 days. In the cisplatin+Epo group, animals received intrapertoneal cisplatin and a daily injection of Epo (100 IU/kg) for 9 days. In the control group, animals received both placebo preparations alone. Para-aminohippuric acid and inulin clearances were determined after 4 and 9 days to evaluate renal blood flow and glomerular filtration rate. In addition, light microscopy and immunohistochemistry examinations were performed, and in situ proliferating cell nuclear antigen (PCNA) staining was done to estimate the degree of renal tubular cell regenerative activity. The potential role of epithelial growth factor (EGF) was evaluated by semi-quantitative assessment of EGF immunostaining. Results Renal blood flow and glomerular filtration rate decreased significantly in cisplatin and cisplatin+Epo groups versus control group at day 4. However, at day 9, they both were significantly greater in cisplatin+Epo-treated animals than in rats that had received cisplatin alone. Tubular cell regeneration was significantly enhanced at day 4 in cisplatin+Epo group, compared with cisplatin and control groups respectively. EGF immunostaining was not significantly different between the three groups. Conclusion Epo significantly enhanced the rate of recovery from acute renal failure induced by cisplatin. PCNA staining indicated that Epo might act directly via stimulation of tubular cell regeneration.

Published
2001
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14. Comparative Effects of Low- and High-Osmolar Contrast Media on the Renal Function during Early Degenerative Gentamicin-lnduced Nephropathy in Rats

Author

Richard Bourbouze, Bruno Koeltz, Alice M. Huntsman, Robin Santus, Jean-Marc Idée, Chantal Jouanneau, Christine Balut, Bruno Bonnemain, and Hélène Beaufils

Subjects
Male, Pathology, medicine.medical_specialty, Ioxaglic acid, Urology, Diatrizoate, Kidney, Nephrotoxicity, Nephropathy, Rats, Sprague-Dawley, Acetylglucosaminidase, Ioxaglic Acid, medicine, Animals, Antibacterial agent, business.industry, Osmolar Concentration, Acute kidney injury, Acute Kidney Injury, medicine.disease, Rats, Contrast medium, medicine.anatomical_structure, Nephrology, Creatinine, Gentamicins, business, Glomerular Filtration Rate, medicine.drug
Abstract

The nephrotoxic potentials of a high-osmolar contrast medium, diatrizoate, and of a low-osmolar contrast medium, ioxaglate, were compared during early degenerative gentamicin-induced nephropathy in the rat. Male rats (13-22/group) were uninephrectomized. Six days later, the aorta was clamped above the renal artery, and either diatrizoate or ioxaglate was administered (1 ml/min for 3 min) via an aortic puncture into the remaining kidney. Some of the rats received chronic treatment with gentamicin (50 mg/kg/day i.m., 4 days), starting 2 days before and ending 1 day after contrast medium administration. Two control groups, only one of which received gentamicin, were subjected to a 3-min renal ischemia. The creatinine clearance (CrCl) per 100 g body weight was determined before and 24 and 48 h after contrast medium injection. A second study (6 rats/group) evaluated urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion and the histologic appearance of the kidneys (blinded analysis) in the same experimental groups. Gentamicin induced a significant decrease in CrCl at baseline (0.35 +/- 0.19 vs. 0.41 +/- 0.19 ml/min; p0.01) and an increase in urinary NAG (128 +/- 92 vs. 39 +/- 57 mumol/h/mmol creatinine; p0.01). Taking into account these differences at baseline, univariate repeated-measures analysis showed that on day 1 diatrizoate caused a more marked decrease in CrCl than ioxaglate (p0.05), whether or not gentamicin was also administered. On day 2, the depressant effect of diatrizoate associated with gentamicin persisted (CrCl vs. day 0 = -0.19 +/- 0.10 ml/min), while that of diatrizoate alone returned to baseline (-0.05 +/- 0.24 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1995
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15. Genetic inhibition of discoidin domain receptor 1 protects mice against crescentic glomerulonephritis

Author

Monique Kerroch, Dominique Guerrot, Pierre Ronco, Chantal Jouanneau, Jean-Claude Dussaule, Laurent Mesnard, Jean-Jacques Boffa, Sophie Vandermeersch, Christos Chatziantoniou, Eric Rondeau, Sandrine Placier, RONCO, Pierre, 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), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
MESH: Mice, Mutant Strains, Kidney Glomerulus, Lupus nephritis, Fluorescent Antibody Technique, Blood Pressure, Biochemistry, Collagen receptor, Blood Urea Nitrogen, Mice, 0302 clinical medicine, Glomerulonephritis, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Animals, MESH: Blood Urea Nitrogen, Receptor, Blood urea nitrogen, MESH: Fluorescent Antibody Technique, 0303 health sciences, biology, Reverse Transcriptase Polymerase Chain Reaction, MESH: Blood Pressure, prevention of chronic kidney disease, renal fibrosis, Immunohistochemistry, MESH: Glomerulonephritis, 3. Good health, Proteinuria, MESH: Receptors, Mitogen, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Receptor Protein-Tyrosine Kinases, Female, Biotechnology, renal inflammation, medicine.medical_specialty, MESH: Mice, Transgenic, Blotting, Western, Mice, Transgenic, Nephrin, 03 medical and health sciences, MESH: Proteinuria, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, MESH: Blotting, Western, Animals, Humans, Molecular Biology, MESH: Mice, Discoidin Domain Receptors, 030304 developmental biology, DDR1, MESH: Humans, business.industry, Receptor Protein-Tyrosine Kinases, MESH: Immunohistochemistry, MESH: Kidney Glomerulus, medicine.disease, Mice, Mutant Strains, Endocrinology, Receptors, Mitogen, biology.protein, business, MESH: Female, Discoidin domain, renal pharmacogenetics
Abstract

International audience; This study investigated the role of discoidin domain receptor 1 (DDR1), a collagen receptor that displays tyrosine-kinase activity, in the development of glomerulonephritis. Crescentic glomerulonephritis was induced in DDR1-deficient mice and their wild-type (WT) littermates as controls, by injection of alloimmune sheep nephrotoxic serum (NTS). Histological, functional and transcriptomic studies were performed. Glomerulonephritis produced a 17-fold increase of DDR1 expression, predominantly in glomeruli. DDR1 deletion protected NTS-treated mice against glomerular disease (proteinuria/creatininuria 5.5±1.1 vs. 13.2±0.8 g/mmol in WT, crescents 12±2 vs. 24±2% of glomeruli, urea 16±2 vs. 28±5 mM), hypertension (123±11 vs. 157±8 mmHg), and premature death (70 vs. 10% survival) (all P

Published
2012
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16. Thrombospondin-1 plays a profibrotic and pro-inflammatory role during ureteric obstruction

Author

Sophie Vandermeersch, Naïke Bigé, Pierre Ronco, Safa Benhassine, Christos Chatziantoniou, Chantal Jouanneau, Jean-Jacques Boffa, Jean-Claude Dussaule, Nasim Shweke, RONCO, Pierre, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), CHU Saint-Antoine [AP-HP], Institut National de la Santé et de la Recherche Médicale and Université Pierre et Marie Curie., and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, Vascular Endothelial Growth Factor A, MESH: Signal Transduction, Time Factors, Apoptosis, MESH: Rats, Sprague-Dawley, Kidney, urologic and male genital diseases, Peritubular capillaries, Nephrectomy, MESH: Mice, Knockout, Rats, Sprague-Dawley, Thrombospondin 1, Mice, MESH: Transforming Growth Factor beta1, 0302 clinical medicine, Fibrosis, MESH: Animals, Renal stem cell, Chemokine CCL2, MESH: Thrombospondin 1, Mice, Knockout, MESH: Collagen Type III, 0303 health sciences, Nephritis, renal progression, renal fibrosis, MESH: Gene Expression Regulation, 3. Good health, medicine.anatomical_structure, Nephrology, 030220 oncology & carcinogenesis, MESH: Fibrosis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Kidney Diseases, medicine.symptom, Inflammation Mediators, MESH: Nephritis, Signal Transduction, Ureteral Obstruction, TGF-β, medicine.medical_specialty, MESH: Rats, MESH: Inflammation Mediators, Inflammation, MESH: Atrophy, Transforming Growth Factor beta1, 03 medical and health sciences, Internal medicine, MESH: Cell Proliferation, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Renal fibrosis, Animals, MESH: Mice, MESH: Chemokine CCL2, 030304 developmental biology, Cell Proliferation, MESH: Capillaries, MESH: Kidney Diseases, business.industry, MESH: Apoptosis, MESH: Vascular Endothelial Growth Factor A, MESH: Chronic Disease, MESH: Time Factors, Kidney metabolism, MESH: Kidney, medicine.disease, MESH: Male, Capillaries, Rats, MESH: Nephrectomy, Disease Models, Animal, Endocrinology, Collagen Type III, Gene Expression Regulation, Chronic Disease, Atrophy, MESH: Ureteral Obstruction, MESH: Disease Models, Animal, business, Kidney disease, Transforming growth factor
Abstract

International audience; Thrombospondin-1 (TSP-1) is an endogenous activator of transforming growth factor-β (TGF-β), and an anti-angiogenic factor, which may prevent kidney repair. Here we investigated whether TSP-1 is involved in the development of chronic kidney disease using rats with unilateral ureteral obstruction, a well-known model to study renal fibrosis. Obstruction of 10 days duration induced inflammation, tubular cell atrophy, dilation, apoptosis, and proliferation, leading to interstitial fibrosis. TSP-1 expression was increased in parallel to that of collagen III and TGF-β. Relief of the obstruction at day 10 produced a gradual improvement in renal structure and function, the reappearance of peritubular capillaries, and restoration of renal VEGF content over a 7- to 15-day post-relief period. TSP-1 expression decreased in parallel with that of TGF-β1 and collagen III. Mice in which the TSP-1 gene was knocked out displayed less inflammation and had better preservation of renal tissue and the peritubular capillary network compared to wild-type mice. Additional studies showed that the inflammatory effect of TSP-1 was mediated, at least in part, by monocyte chemoattractant protein-1 and activation of the Th17 pathway. Thus, TSP-1 is an important profibrotic and inflammatory mediator of renal disease. Blockade of its action may be a treatment against the development of chronic kidney disease.

Published
2012
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17. Autoantibodies specific for the phospholipase A2 receptor in recurrent and De Novo membranous nephropathy

Author

Laurent Mesnard, Eric Rondeau, Christiane Mousson, G. Dautin, Pierre Ronco, Hanna Debiec, Chantal Jouanneau, L. Martin, 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 ), Urgences Néphrologiques & Transplantation Rénale, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne ( UB ), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), EFS Bourgogne Franche-Comté ( EFS-BFC ), Etablissement Français du Sang (EFS), Service de néphrologie (CHU de Dijon), Agence de la Biomédecine, Fondation pour la Recherche Médicale and 'Association pour l'Utilisation du Rein Artificiel' (AURA). H.D. is the recipient of a 'Contrat d'Interface' from Assistance Publique-Hôpitaux de Paris., 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), Université de Bourgogne (UB), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Etablissement Français du Sang de Bourgogne Franche-Comté (site de Dijon) (EFS BFC (site de Dijon)), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), RONCO, Pierre, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)

Subjects
Male, MESH : Recurrence, MESH : DNA, Complementary, MESH: Glomerulonephritis, Membranous, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Glomerulonephritis, Membranous, 0302 clinical medicine, Recurrence, [ SHS.INFO ] Humanities and Social Sciences/Library and information sciences, Immunology and Allergy, Medicine, MESH: Autoantibodies, MESH : Fluorescent Antibody Technique, Direct, Pharmacology (medical), MESH : Female, MESH : Glomerulonephritis, Membranous, Receptor, MESH: Middle Aged, biology, MESH : Receptors, Phospholipase A2, Glomerulonephritis, Middle Aged, respiratory system, MESH : Adult, 3. Good health, Fluorescent Antibody Technique, Direct, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, lipids (amino acids, peptides, and proteins), De novo, Antibody, MESH: Fluorescent Antibody Technique, Direct, Adult, DNA, Complementary, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, MESH : Male, macromolecular substances, [SHS.INFO] Humanities and Social Sciences/Library and information sciences, 03 medical and health sciences, recurrent, Antigen, Membranous nephropathy, stomatognathic system, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH : Autoantibodies, MESH: Receptors, Phospholipase A2, Humans, MESH : Middle Aged, Direct fluorescent antibody, PLA2R1, Autoantibodies, Transplantation, MESH: Humans, business.industry, Receptors, Phospholipase A2, MESH : Humans, Autoantibody, membranous nephropathy, MESH: Adult, MESH: DNA, Complementary, medicine.disease, equipment and supplies, MESH: Male, MESH: Recurrence, Immunology, biology.protein, business, MESH: Female
Abstract

International audience; Recent findings in idiopathic membranous nephropathy (MN) suggest that in most patients, the disease is because of anti-phospholipase A(2) receptor (PLA(2) R1) autoantibodies. Our aim was to analyze the prevalence and significance of anti-PLA(2) R1 antibodies in recurrent and de novo MN after transplantation. We assessed circulating PLA(2) R1 autoantibodies by a direct immunofluorescence assay based on human embryonic kidney cells transfected with a PLA(2) R1 cDNA, and the presence of PLA(2) R1 antigen in immune deposits. We showed that PLA(2) R1 was involved in 5 of 10 patients with recurrent MN, but in none of the 9 patients with de novo MN. We also showed a marked heterogeneity in the kinetics and titers of anti-PLA(2) R1, which may relate to different pathogenic potential. We provide evidence that some patients with PLA(2) R1-related idiopathic MN and anti-PLA(2) R1 antibodies at the time of transplantation will not develop recurrence. Because PLA(2) R1 autoantibody was not always associated with recurrence, its predictive value should be carefully analyzed in prospective studies.

Published
2011
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18. Asymmetric dimethylarginine (ADMA) induces chronic kidney disease through a mechanism involving collagen and TGF-β1 synthesis

Author

Christos Chatziantoniou, Jean-Claude Dussaule, Chantal Jouanneau, Pierre Ronco, Nasim Shweke, Jean-Jacques Boffa, Fabrice Mihout, and Naïke Bigé

Subjects
Male, medicine.medical_specialty, Mice, Inbred Strains, urologic and male genital diseases, Arginine, Kidney, Peritubular capillaries, Pathology and Forensic Medicine, Nitric oxide, Transforming Growth Factor beta1, chemistry.chemical_compound, Mice, Fibrosis, Internal medicine, medicine, Renal fibrosis, Animals, RNA, Messenger, Endothelial dysfunction, Enzyme Inhibitors, Renal Insufficiency, Chronic, Endothelin-1, business.industry, Reverse Transcriptase Polymerase Chain Reaction, medicine.disease, Hypoxia-Inducible Factor 1, alpha Subunit, Oxidative Stress, Endocrinology, medicine.anatomical_structure, NG-Nitroarginine Methyl Ester, chemistry, Gene Expression Regulation, Hypertension, Collagen, Nitric Oxide Synthase, Asymmetric dimethylarginine, business, Kidney disease
Abstract

Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, is accumulated in plasma during chronic kidney disease (CKD). It is considered an independent mortality and cardiovascular risk factor in CKD patients. To test the involvement of ADMA in CKD progression, we investigated the effects of chronic ADMA administration on renal structure and compared these effects with NG-nitro-L-arginine methyl ester (L-NAME) treatment, a widely used exogenous inhibitor of NOS that induces CKD. Three groups of uninephrectomized mice were studied: ADMA (60 mg/kg per day), L-NAME (60 mg/kg per day), and isotonic saline (control) were infused through osmotic mini-pumps for 8 weeks. ADMA and L-NAME induced hypertension (PAS 167 ± 16 and 168 ± 10 versus 100 ± 4 mmHg, p < 0.01, respectively). High level of ADMA was associated with increased renal oxidative stress. ADMA treatment induced glomerular and vascular fibrosis as evidenced by the elevated deposits of collagen I, III, and fibronectin (p < 0.01). A similar profile was observed in the L-NAME group. Mice treated with ADMA had reduced peritubular capillaries versus controls (p < 0.01). Collagen I mRNA expression and renal TGF-β1 concentrations were higher in the ADMA and L-NAME groups. Increased level of TGF-β1 was associated with a significant rise of HIF-1α and endothelin-1 expression. These results demonstrate for the first time that elevated concentrations of ADMA are associated with the development of renal fibrosis. These data suggest that in pathophysiological conditions of endothelial dysfunction, the exaggerated endogenous synthesis of ADMA could contribute to CKD progression by favouring hypertension, extracellular matrix synthesis, and rarefaction of peritubular capillaries.

Published
2010

19. HIV-associated IgA nephropathy—A post-mortem study

Author

C. Katlama, J. J. Hauw, Hélène Beaufils, Chantal Jouanneau, and V. Sazdovitch

Subjects
Immunoglobulin A, Transplantation, Aids patients, Pathology, medicine.medical_specialty, Kidney, biology, business.industry, Urinary system, Human immunodeficiency virus (HIV), Immunofluorescence Microscopy, medicine.disease, medicine.disease_cause, Nephropathy, Muscle hypertrophy, medicine.anatomical_structure, Nephrology, medicine, biology.protein, business
Abstract

Between November 1983 and December 1991, we undertook a systematic study of kidney in deceased AIDS patients using light and immunofluorescence microscopy. Among the 116 examined kidneys (from 106 men and 10 women), nine (7.75%) showed diffuse mesangial IgA deposits. By light microscopy, glomerular lesions were absent or moderate (mesangial hypertrophy or some mesangial deposits). Urinary abnormalities were mild in all cases. Our study shows that the association between IgA nephropathy and HIV infection is not rare, and a review of the literature disclosed 18 reported cases. Some reported immunopathogenic data support the possibility of a link between HIV infection and IgA nephropathy.

Published
1995
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20. Chronic cisplatin nephropathy in rats

Author

Chantal Jouanneau, Georges Brillet, Claude Jacobs, Gilbert Deray, P. Maksud, Martine Dubois, Richard Bourbouze, and Hélène Beaufils

Subjects
Male, medicine.medical_specialty, Urinary system, medicine.medical_treatment, Renal function, Kidney, Nephropathy, Rats, Sprague-Dawley, Excretion, Internal medicine, Animals, Medicine, Cisplatin, Transplantation, Chemotherapy, Dose-Response Relationship, Drug, business.industry, Body Weight, medicine.disease, Rats, Endocrinology, medicine.anatomical_structure, Nephrology, Creatinine, Toxicity, business, Glomerular Filtration Rate, medicine.drug
Abstract

The long-term renal effects of cisplatin have been very poorly studied. Therefore we investigated the chronic renal effects of various doses of cisplatin in three groups of male Sprague-Dawley rats. Group I received two injections of 5 mg/kg body weight (bw) at 4-week intervals, group II four injections of 2.5 mg/kg bw at 4-weeks intervals, and group III one injection of 5 mg/kg bw and four injections of 2.5 mg/kg bw at 4-weeks intervals. Controls received an equivalent amount of isotonic saline. Each group was evaluated 1, 3, or 6 months after the last injection of cisplatin. One, 3 and 6 months after the last injection, cisplatin induced a marked decrease in glomerular filtration rate (GFR) evaluated as clearance of [99mTc]DTPA and creatinine clearance in all treated rats. Urinary NAG excretion remained unaltered. At 3 months post-cisplatin treatment GFR was significantly less (P < 0.05) in group III (0.18 +/- 0.02 ml/min/100 g bw) when compared with group I (0.23 +/- 0.02 ml/min/100 g bw) or II (0.23 +/- 0.04 ml/min/100 g bw). In group I GFR was similar 1 month (0.24 +/- 0.02), 3 months (0.23 +/- 0.02) and 6 months (0.23 +/- 0.03 ml/min/100 g bw) after cisplatin treatment. Cisplatin induced atrophy and dilatation of tubules with mononuclear cell infiltration associated with cyst formation. The glomerular and tubulointerstitial lesions were significantly enhanced in group III when compared with groups I and II. This study indicates that repeated administration of cisplatin may induce a chronic tubulointerstitial nephropathy associated with a marked decrease in GFR, which is stable over time. The incidence and severity of chronic cisplatin toxicity is dose-related and is not modified by dividing the dose.

Published
1993
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