Author: "Pierre, Ronco" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Pierre, Ronco"' showing total 361 results

Start Over Author "Pierre, Ronco" Topic medicine

361 results on '"Pierre, Ronco"'

1. Combining robust urine biomarkers to assess chronic kidney disease progressionResearch in context

Author: Frank Bienaimé, Mordi Muorah, Marie Metzger, Melanie Broeuilh, Pascal Houiller, Martin Flamant, Jean-Philippe Haymann, Jacky Vonderscher, Jacques Mizrahi, Gérard Friedlander, Bénédicte Stengel, Fabiola Terzi, François Vrtovsnik, Eric Daugas, Emmanuelle Vidal-Petiot, Christian Jacquot, Alexandre Karras, Stéphane Roueff, Eric Thervet, Pascal Houillier, Marie Courbebaisse, Dominique Eladari et Gérard Maruani, Pablo Urena-Torres, Jean-Jacques Boffa, Pierre Ronco, H. Fessi, Eric Rondeau, Emmanuel Letavernier, and Nahid Tabibzadeh
Subjects: Chronic kidney disease progression, Urinary biomarkers, EGF, TGF-α, CCL2, NGAL, Medicine, Medicine (General), R5-920
Abstract: Summary: Background: Urinary biomarkers may improve the prediction of chronic kidney disease (CKD) progression. Yet, data reporting the applicability of most commercial biomarker assays to the detection of their target analyte in urine together with an evaluation of their predictive performance are scarce. Methods: 30 commercial assays (ELISA) were tested for their ability to quantify the target analyte in urine using strict (FDA-approved) validation criteria. In an exploratory analysis, LASSO (Least Absolute Shrinkage and Selection Operator) logistic regression analysis was used to identify potentially complementary biomarkers predicting fast CKD progression, determined as the 51CrEDTA clearance-based measured glomerular filtration rate (mGFR) decline (>10% per year) in a subsample of 229 CKD patients (mean age, 61 years; 66% men; baseline mGFR, 38 mL/min) from the NephroTest prospective cohort. Findings: Among the 30 assays, directed against 24 candidate biomarkers, encompassing different pathophysiological mechanisms of CKD progression, 16 assays fulfilled the FDA-approved criteria. LASSO logistic regressions identified a combination of five biomarkers including CCL2, EGF, KIM1, NGAL, and TGF-α that improved the prediction of fast mGFR decline compared to the kidney failure risk equation variables alone: age, gender, mGFR, and albuminuria. Mean area under the curves (AUC) estimated from 100 re-samples was higher in the model with than without these biomarkers, 0.722 (95% confidence interval 0.652–0.795) vs. 0.682 (0.614–0.748), respectively. Fully-adjusted odds-ratios (95% confidence interval) for fast progression were 1.87 (1.22, 2.98), 1.86 (1.23, 2.89), 0.43 (0.25, 0.70), 1.10 (0.71, 1.83), 0.55 (0.33, 0.89), and 2.99 (1.89, 5.01) for albumin, CCL2, EGF, KIM1, NGAL, and TGF-α, respectively. Interpretation: This study provides a rigorous validation of multiple assays for relevant urinary biomarkers of CKD progression which combination may improve the prediction of CKD progression. Funding: This work was supported by Institut National de la Santé et de la Recherche Médicale, Université de Paris, Assistance Publique Hôpitaux de Paris, Agence Nationale de la Recherche, MSDAVENIR, Pharma Research and Early Development Roche Laboratories (Basel, Switzerland), and Institut Roche de Recherche et Médecine Translationnelle (Paris, France).
Published: 2023
Full Text: View/download PDF

2. Treatment needs and expectations for Fabry disease in France: development of a new Patient Needs Questionnaire

Author: Esther Noël, Bertrand Dussol, Didier Lacombe, Najya Bedreddine, Alain Fouilhoux, Pierre Ronco, Delphine Genevaz, Soumeya Bekri, Albert Hagège, Frédérique Dupuis-Siméon, Valérie Derrien Ansquer, Dominique P. Germain, and Olivier Lidove
Subjects: Fabry disease, Patient association, Patient-reported outcome measure, Patient self-reported tool, Patient Needs Questionnaire, Psychometric analysis, Medicine
Abstract: Abstract Background Fabry disease (FD) is a rare, X-linked, inherited lysosomal disease caused by absent or reduced α-galactosidase A activity. Due to the heterogeneity of disease presentation and progression, generic patient-reported outcome (PRO) tools do not provide accurate insight into patients’ daily lives and impact of disease specific treatments. Also, the French National Health Authority, (HAS) actively encourages a patient-centric approach to improve the quality of care throughout the patient journey. In response to this initiative, we aimed to develop and validate a specific, self-reported, Patient Needs Questionnaire for people living with Fabry disease to appraise patient needs and expectations towards their treatment (PNQ Fabry). This endeavour was led with the help of French patient associations (APMF & VML) and dedicated expert centres. PNQ Fabry was developed according to the FDA/EMA methodologies and best practices for the development of PRO tools in rare diseases. Our approach comprised of three steps, as follows: concept elicitation and item generation, item reduction, and final validation of the questionnaire through a two-stage survey. Results Intrinsic and extrinsic reliability was established, using a validated benchmark questionnaire. With the invaluable help of patient associations, we recruited a satisfactory population in this rare disease setting, to ensure robust participation to validate our PNQ (final number of questionnaires: 76). At the end of the process, a 26-item patient-reported questionnaire was obtained with excellent psychometric properties, exhibiting very satisfactory measurement outcomes for reliability and validity. The results of this initiative demonstrate that the PNQ Fabry is accurate, suitable and tailored to FD patients, as it addresses themes identified during patient interviews, that were further validated through statistical analyses of quantitative surveys. An ongoing phase IV study is using this tool. Conclusion We believe the PNQ Fabry will be a reliable and insightful tool in clinical practice, to improve patient management in FD.
Published: 2019
Full Text: View/download PDF

3. Contactin 1, a Potential New Antigen Target in Membranous Nephropathy: A Case Report

Author: Domenico Santoro, Pierre Ronco, Hanna Debiec, Elisa Longhitano, Antonella Barreca, Giorgina Barbara Piccoli, Massimo Torreggiani, Elisa Vegezzi, Massimo Russo, Antonio Toscano, and Anna Mazzeo
Subjects: Pathology, medicine.medical_specialty, Proteinuria, medicine.diagnostic_test, biology, business.industry, Autoantibody, medicine.disease, Western blot, Membranous nephropathy, Antigen, Nephrology, Biopsy, medicine, biology.protein, medicine.symptom, Antibody, business, Nephrotic syndrome
Abstract: Several novel antigens have recently been characterized in membranous nephropathy (MN), but those involved in the rare cases of MN associated with inflammatory neuropathies (IN) remain elusive. Although several antibody specificities were identified in the serum, there is no evidence so far for their deposition in glomeruli. We report the case of a 73 y/o woman who was referred because of subacute onset of proximal asymmetric lower limb weakness together with ataxic gait. She was diagnosed with IN. Blood tests showed an eGFR of 73 ml/min/1.73m2, hypoalbuminemia (2.89 g/dl) and proteinuria (3.6 g/24h). Autoantibodies (ANA, ENA, DNA, LAC, anti-cardiolipin, ANCA) were undetectable. Serum Ig and complement levels were normal. A kidney biopsy with electron microscopy examination showed a classical picture of MN. Anti-PLA2R antibody was negative in the serum and PLA2R and THSD7A antigens were not detected in kidney tissue. Anti-contactin1 (CNTN1) antibody was found by ELISA at 1:100 serum dilution and shown to be mostly of IgG4 subclass by Western blot. CNTN1 antigen was co-localized with IgG4 within immune deposits by confocal microscopy. This observation suggests a pathophysiological link between IN and MN. CNTN1 should be considered as a potential candidate antigen involved in MN and tested in PLA2R negative forms associated with IN.
Published: 2022

4. Improving Clinical Trials for Anticomplement Therapies in Complement-Mediated Glomerulopathies: Report of a Scientific Workshop Sponsored by the National Kidney Foundation

Author: Minnie M. Sarwal, Nicole Arceneaux, Jonathan Barratt, Mark D. Stegall, Christine B. Sethna, Debbie S. Gipson, Shadab Ali, Richard J.H. Smith, Matthew C. Pickering, Lindsey Fuller, Brad H. Rovin, Ashley Frazer-Abel, Carla M. Nester, Rasheed Gbadegesin, Fernando C. Fervenza, Gerald B. Appel, Samir V. Parikh, Daniel C. Cattran, Véronique Frémeaux-Bacchi, Cathie Spino, Sanjay Ram, Pierre Ronco, Laura Bailey-Wickins, Paolo Cravedi, Jonathan J. Hogan, Joshua M. Thurman, Laurence H. Beck, John D. Mahan, Marina Vivarelli, Isa Ashoor, Michelle N. Rheault, Elif Erkan, David L. Feldman, Richard J. Quigg, Richard A. Lafayette, Peter S. Heeger, Andrew S. Bomback, Moglie le Quintrec-Donnette, Michelle A. Hladunewich, Christoph Licht, Krzysztof Kiryluk, and Howard Trachtman
Subjects: medicine.medical_specialty, business.industry, Clinical study design, MEDLINE, Foundation (evidence), Complement (complexity), Clinical trial, Nephrology, medicine, Patient representatives, Intensive care medicine, Risk assessment, business, Therapeutic strategy
Abstract: Blocking the complement system as a therapeutic strategy has been proposed for numerous glomerular diseases but presents a myriad of questions and challenges, not the least of which is demonstrating efficacy and safety. In light of these potential issues and because there are an increasing number of anti-complement therapy trials either planned or underway, the National Kidney Foundation (NKF) facilitated an all-virtual format scientific workshop entitled, "Improving Clinical Trials for Anti-complement Therapies in Complement-mediated Glomerulopathies." Attended by patient representatives and experts in glomerular diseases, complement physiology, and clinical trial design, the aim of this workshop was to develop standards applicable for designing and conducting clinical trials for anti-complement therapies across a wide spectrum of complement-mediated glomerulopathies. Discussions focused on study design, subject risk assessment and mitigation, laboratory measurements and biomarkers to support these studies, and identification of optimal outcome measures to detect benefit, specifically for trials in complement-mediated diseases. This report summarizes the discussions from this workshop and outlines consensus recommendations.
Published: 2022

5. Executive summary of the KDIGO 2021 Guideline for the Management of Glomerular Diseases

Author: Frank Bridoux, David Jayne, Yusuke Suzuki, Amy Earley, Kelly A. Burdge, Marina Vivarelli, Zhihong Liu, Jai Radhakrishnan, Adrian Liew, Keisha L. Gibson, Marcello Tonelli, Richard J. Glassock, Sydney C.W. Tang, Sharon G. Adler, Jan-Stephan F. Sanders, H. Terence Cook, Jonathan C. Craig, Vladimir Tesar, Sanjeev Sethi, Jonathan Barratt, Pierre Ronco, Elizabeth M. Rave, Michael Cheung, Brad H. Rovin, David J. Tunnicliffe, Carla M. Nester, Juan M. Mejia-Vilet, Vivekanand Jha, Martin Howell, Fernando C. Fervenza, Tak Mao Chan, Lyubov Lytvyn, Jürgen Floege, Jack F.M. Wetzels, Heather N. Reich, Groningen Kidney Center (GKC), Groningen Institute for Organ Transplantation (GIOT), Jayne, David [0000-0002-1712-0637], and Apollo - University of Cambridge Repository
Subjects: Adult, medicine.medical_specialty, Evidence-based practice, Kidney, Glomerulonephritis, Membranous, anti-GBM, Nephropathy, IgA vasculitis, Glomerulonephritis, Focal segmental glomerulosclerosis, systematic review, Membranous nephropathy, evidence-based, medicine, Humans, complement, Minimal change disease, C3, Child, Intensive care medicine, glomerular diseases, infection-related glomerulonephritis, KDIGO, lupus nephritis, ANCA, nephrotic syndrome, business.industry, MPGN, Nephrosis, Lipoid, membranous nephropathy, AAV, Glomerulonephritis, IGA, IgA nephropathy, Guideline, medicine.disease, FSGS, minimal change disease, Systematic review, Nephrology, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, guideline
Abstract: Kidney international 100(4), 753-779 (2021). doi:10.1016/j.kint.2021.05.015, Published by Elsevier, New York, NY
Published: 2021

6. A Fresh Perspective on Monoclonal Gammopathies of Renal Significance

Author: Pierre Ronco, Pierre Aucouturier, Vivette D. D'Agati, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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 d'immunologie et hématologies biologiques [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Columbia University Medical Center (CUMC), Columbia University [New York], Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Aucouturier, Pierre, Centre de Recherche Saint-Antoine (CRSA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunoglobulin Isotypes, 030232 urology & nephrology, Review, 030204 cardiovascular system & hematology, Bioinformatics, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, glomerulopathy, 03 medical and health sciences, 0302 clinical medicine, Medicine, immunoglobulin isotypes, immunoglobulin variable regions, business.industry, monoclonal gammopathy, monoclonalgammopathy, IgG3, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, monotypic deposits, 3. Good health, Monoclonal gammopathy, PGNMID, Nephrology, Monoclonal, [SDV.IMM]Life Sciences [q-bio]/Immunology, Treatment strategy, medicine.symptom, business, Clone (B-cell biology)
Abstract: International audience; Monoclonal gammopathies of renal significance (MGRS) encompass a remarkable variety of kidney diseases that result from intrinsic nephrotoxic properties of certain monoclonal Igs or their subunits. Effective disease-modifying treatments rely on the targeting of a malignant B-cell clone that may be demonstrable but often is quite hypothetical. Hence, convincing arguments for the genuine monoclonal character of the causative mono-isotypic Ig tissue deposits is needed for design of appropriate treatment strategies. The purpose of this article was to critically analyze distinct situations of suspected MGRS that occur in the practice of pathologists, nephrologists, hematologists, and immunologists. A particular focus of interest is the group of conditions known as proliferative glomerulonephritis with mono-isotypic immunoglobulin deposits (PGNMIDs), which illustrates the difficulties and ambiguities surrounding a definitive assignment of MGRS status.
Published: 2021

7. The Exostosin Immunohistochemical Status Differentiates Lupus Membranous Nephropathy Subsets With Different Outcomes

Author: Xavier Belenfant, Philippe Rouvier, Pierre Ronco, Isabelle Brocheriou, Emmanuel Esteve, Michèle Saïdi, David Buob, Tim Ulinski, Sophie Tuffet, Hanna Debiec, Zahir Amoura, Makoto Miyara, 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'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [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), Unité de Recherche Clinique de l’Est Parisien [CHU Saint-Antoine] (URC-EST), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-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)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Centre Hospitalier Intercommunal André Grégoire [Montreuil] (CHI André Gregoire), Service de néphrologie et pédiatrie générale [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), 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], 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)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Trousseau [APHP], HAL-SU, Gestionnaire, and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP]
Subjects: Pathology, medicine.medical_specialty, 030232 urology & nephrology, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 03 medical and health sciences, 0302 clinical medicine, renal biopsy, systemic lupus erythematosus, Membranous nephropathy, Research Letter, medicine, skin and connective tissue diseases, 030304 developmental biology, 0303 health sciences, Systemic lupus erythematosus, medicine.diagnostic_test, business.industry, membranous nephropathy, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 3. Good health, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Nephrology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, exostosin, immunohistochemistry, Immunohistochemistry, Renal biopsy, business
Abstract: International audience; Exostosin (EXT) 1 and EXT2 proteins are recently discovered major components of the subepithelial deposits in a subset of patients with membranous nephropathy (MN).1,2 Although the detection of EXT1/2 seems to be a distinctive feature of MN related to systemic lupus erythematosus (SLE),1 the exact frequency of EXT-positive, SLE-associated MN (SLE-MN) and its potential clinical significance are not well determined.Here, we retrospectively evaluated 86 consecutive patients with biopsy-proven pure class 5 SLE-MN diagnosed between January 2010 and December 2018 in 2 nephropathology centers (La Pitié Salpêtrière and Tenon hospitals) in Paris, France; mixed classes (3 + 5 and 4 + 5 of the 2003 ISN/Renal Pathology Society classification)3 were excluded.
Published: 2021

8. Immune response to SARS-CoV-2 infection and vaccination in patients receiving kidney replacement therapy

Author: T. Alp Ikizler, Pierre Ronco, Brad H. Rovin, and P. Toby Coates
Subjects: Male, 0301 basic medicine, COVID-19 Vaccines, medicine.medical_treatment, 030232 urology & nephrology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Renal Dialysis, Immunity, medicine, Humans, Renal replacement therapy, Pandemics, Letter to the Editor, Kidney transplantation, Dialysis, Aged, SARS-CoV-2, business.industry, Immunogenicity, Vaccination, Antibody titer, COVID-19, Middle Aged, medicine.disease, Kidney Transplantation, Renal Replacement Therapy, Outcome and Process Assessment, Health Care, 030104 developmental biology, Nephrology, Immunology, Commentary, Female, business
Abstract: In this issue of Kidney International, the initial experience regarding the immunogenicity of prior coronavirus disease 2019 (COVID-19) infection and the response to the COVID-19 vaccines among patients on maintenance dialysis and kidney transplant recipients is summarized. Preliminary data suggest that there is durability of immune response after COVID-19 infection. Although immune response to the first dose of vaccine is less in infection-naïve patients than healthy individuals in both groups, after the second vaccine dose a significant portion of patients receiving maintenance dialysis develop robust antibody titers, whereas kidney transplant recipients show a less-strong immune response.
Published: 2021

9. Contactin-1–associated membranous nephropathy: complete immunologic and clinical remission with rituximab

Author: Pierre Ronco, Emmanuelle Plaisier, Adeline Not, Hanna Debiec, and David Buob
Subjects: medicine.medical_specialty, Contactin 1, Membranous nephropathy, Nephrology, business.industry, Internal medicine, Medicine, Rituximab, business, medicine.disease, Gastroenterology, medicine.drug
Published: 2021

10. Time to Abandon Kidney Biopsy to Diagnose Membranous Nephropathy?

Author: Emmanuelle Plaisier and Pierre Ronco
Subjects: Nephrology, Transplantation, Kidney, medicine.medical_specialty, Pathology, biology, medicine.diagnostic_test, Epidemiology, business.industry, Editorials, Glomerulosclerosis, Disease, Critical Care and Intensive Care Medicine, medicine.disease, Serology, medicine.anatomical_structure, Membranous nephropathy, Internal medicine, Biopsy, medicine, biology.protein, Antibody, business
Abstract: The discovery of phospholipase A2 receptor (PLA2R) antibody by Beck and associates ([1][1]) has been transformative for the diagnosis of membranous nephropathy and for the monitoring of patients affected with the disease. Less than 2 years after this discovery, serologic tests were developed: first
Published: 2021

11. When contactin antibodies hit the podocyte: a new neurorenal syndrome

Author: Hanna Debiec and Pierre Ronco
Subjects: Pathology, medicine.medical_specialty, Kidney, biology, Podocytes, business.industry, Cell adhesion molecule, Disease, medicine.disease, Glomerulonephritis, Membranous, Antibodies, Podocyte, medicine.anatomical_structure, Membranous nephropathy, Antigen, Contactins, Nephrology, biology.protein, Humans, Medicine, In patient, Antibody, business
Abstract: Membranous nephropathy can be associated with various etiologies and antigens. In this issue of Kidney International, Le Quintrec et al. described contactin-1 cell adhesion molecule as a novel target antigen shared by the peripheral nerve and podocyte in patients with neurological disease and membranous nephropathy.
Published: 2021

12. Prognostic value of PLA2R autoimmunity detected by measurement of anti-PLA2R antibodies combined with detection of PLA2R antigen in membranous nephropathy: A single-centre study over 14 years.

Author: Franck Pourcine, Karine Dahan, Fabrice Mihout, Marine Cachanado, Isabelle Brocheriou, Hanna Debiec, and Pierre Ronco
Subjects: Medicine, Science
Abstract: INTRODUCTION:Clinical course of membranous nephropathy (MN) is difficult to predict. Measurement of circulating anti-PLA2R autoantibodies (PLA2R-Ab) and detection in immune deposits of PLA2R antigen (PLA2R-Ag) are major advances in disease understanding. We evaluated the clinical significance of these biomarkers. METHODS:In this 14-year retrospective study, we collected data from 108 MN patients and assessed the relationship between clinical course, PLA2R-Ab and PLA2R-Ag. We also assessed THSD7A status. RESULTS:Eighty-five patients suffered from primary MN (PMN) and 23 patients from a secondary form. The median follow-up was 30.4 months [interquartile range, 17.7;56.7]. Among the 77 patients with PMN and available serum and/or biopsy, 69 (89.6%) had PLA2R-related disease as shown by anti-PLA2R-Ab and/or PLA2R-Ag, while 8 patients (8/77, 10.4%) were negative for both. There was no significant difference between these two groups in age at diagnosis and outcome assessed by proteinuria, serum albumin level and eGFR. Two of the 8 negative patients were positive for THSD7A. In patients with PLA2R related PMN, younger age, lower proteinuria, higher eGFR, and lower PLA2R-Ab level at baseline and after 6 months were associated with remission of proteinuria. Initial PLA2R-Ab titer ≤ 97.6 RU/mL and complete depletion of PLA2R-Ab within 6-months were significantly associated with spontaneous remission at the end of follow-up. In rituximab treated patients, lower PLA2R-Ab titer at initiation of treatment, and absence of PLA2R-Ab and higher serum albumin level at 3 months were significantly associated with remission. Noticeably, 81.8% of the patients who achieved remission completely cleared PLA2R-Ab. Depletion of PLA2R-Ab and increase of serum albumin level preceded the decrease of proteinuria. CONCLUSION:Assessment of PLA2R autoimmunity is essential for patient management. Combination of PLA2R-Ab and PLA2R-Ag increases diagnosis sensitivity. PLA2R-Ab titer is a biomarker of disease severity at initial assessment, and the kinetics of the antibody are significantly correlated to disease evolution.
Published: 2017
Full Text: View/download PDF

13. HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients

Author: Ann M. Moyer, Petra Mrázová, Guillaume Canaud, Jack F.M. Wetzels, Nadhir Yousfi, Maryvonne Hourmant, Christophe Legendre, Manish J. Gandhi, Vladimir Tesar, Mariam P. Alexander, Ondrej Viklický, Christiane Mousson, Hanna Debiec, Pierre Ronco, Philippe Rieu, Valérie Dubois, Anne-Els van de Logt, Paul Brenchley, Sylvain Guibert, Vincent Vuiblet, Charlène Levi, Patrick Hamilton, Armando Torres, Bruno Moulin, Eric Letouzé, Josep M. Cruzado, José Aurelio Ballarín Castan, Lena Berchtold, Gabriel Choukroun, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Geneva University Hospital (HUG), 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), Mayo Clinic [Rochester], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service Néphrologie et transplantation rénale Adultes [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), Radboud University Medical Center [Nijmegen], University of Manchester [Manchester], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biospectroscopie Translationnelle - EA 7506 (BIOSPECT), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), University of Barcelona, Universidad de La Laguna [Tenerife - SP] (ULL), Charles University [Prague] (CU), Institute for Clinical and Experimental Medicine (IKEM), Centre hospitalier universitaire de Nantes (CHU Nantes), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), CHU Amiens-Picardie, Département de Néphrologie [CHU Necker], Service de néphrologie et de 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), Gestionnaire, Hal Sorbonne Université, 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 Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, 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'Urgences néphrologiques et transplantation rénale [CHU Tenon], CHU Tenon [AP-HP], 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, Oncology, medicine.medical_specialty, Linkage disequilibrium, recurrence, HLA-D, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Locus (genetics), Single-nucleotide polymorphism, Glomerulonephritis, Membranous, Polymorphism, Single Nucleotide, genetic risk score, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Internal medicine, medicine, Humans, genetics, PLA2R1, Alleles, Retrospective Studies, Genetic testing, next generation sequencing, medicine.diagnostic_test, business.industry, Donor selection, Receptors, Phospholipase A2, membranous nephropathy, Retrospective cohort study, medicine.disease, Kidney Transplantation, 3. Good health, [SDV] Life Sciences [q-bio], Transplantation, 030104 developmental biology, Nephrology, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, transplantation
Abstract: Contains fulltext : 234032.pdf (Publisher’s version ) (Closed access) Recurrence of primary membranous nephropathy after transplantation occurs in up to 44% of patients and is driven by PLA2R antibody. Here, we asked whether genetic determinants could improve risk prediction. First, we sequenced PLA2R1 and HLA-D loci in 248 patients with primary membranous nephropathy and identified two independent single nucleotide polymorphisms (SNPs) at risk for primary membranous nephropathy at each locus. These were rs9271188 (intergenic between HLA-DRB1 and HLA-DQA1,) and rs9275086 (intergenic between HLA-DQB1 and HLA-DQA2) at the HLA-D locus along with rs6726925 and rs13018963 at the PLA2R1 locus. Then we investigated whether primary membranous nephropathy at-risk variants were associated with recurrence in a retrospective cohort of 105 donor-recipient pairs and a replication cohort of 40 pairs. Seven SNPs located between HLA-DRB1 and HLA-DQA1 in linkage disequilibrium with rs9271188, and three SNPs in the PLA2R1 region predicted recurrence when presented by the donor, but not when presented by the recipient. The two SNPs in the HLA-D region most strongly associated with recurrence (rs9271705 and rs9271550) were confirmed in the replication cohort. A genetic risk score based on the two best predictors at each locus (rs9271705, rs9271550, rs17830558, and rs3828323) identified a group of patients with high risk of recurrence. Thus, our results suggest that the graft contributes to recurrence of primary membranous nephropathy through the disease susceptibility HLA-D and PLA2R1 SNPs in an autoimmune milieu. Further studies are needed before implementation of genetic testing for these in donor selection.
Published: 2021

14. The clinicopathologic spectrum of segmental membranous glomerulopathy

Author: Pietro A. Canetta, M. Barry Stokes, Glen S. Markowitz, Satoru Kudose, Dominick Santoriello, Vivette D. D'Agati, Hanna Debiec, Andrew S. Bomback, Pierre Ronco, and Ibrahim Batal
Subjects: 0301 basic medicine, medicine.medical_specialty, Nephrotic Syndrome, Biopsy, medicine.medical_treatment, 030232 urology & nephrology, Renal function, Immunofluorescence, Glomerulonephritis, Membranous, Stain, Gastroenterology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, Stage (cooking), Retrospective Studies, Creatinine, medicine.diagnostic_test, business.industry, Immunosuppression, medicine.disease, Staining, 030104 developmental biology, chemistry, Nephrology, business, Nephrotic syndrome, Immunosuppressive Agents
Abstract: Membranous glomerulopathy (MGN) is characterized by global subepithelial immune deposits that stain most intensely by immunofluorescence for IgG. Here we describe the clinical and pathologic findings in a cohort of patients with MGN in which, by definition, only segmental immune deposits are present. This rare variant, termed segmental MGN (sMGN), is poorly characterized. We retrospectively identified all patients with sMGN diagnosed at Columbia University from January 2010 to October 2018, excluding those with systemic lupus erythematosus. Data on presenting features, pathologic findings, and outcomes were collected. Fifty cases of sMGN were identified, representing 2.5% of MGN. In 21 of 50 biopsies, there was an alternative, predominant disease process. The remaining 29 patients with isolated sMGN had a median creatinine of 0.97 mg/dl, median 24-hour urine protein 3.1 g/day, and 32% had nephrotic syndrome. Staining for NELL-1 (a protein kinase C binding protein) was positive in five of 17 cases. Staining for PLA2R, THSD7A, and exostosin 1 (autoantigens in primary MGN) was negative in all biopsies evaluated. Ultrastructural evaluation revealed predominantly early stage sMGN (stage 1 or 1-2 in 14/29). Follow-up was available for 21 of the 29 patients with isolated sMGN (median 12 months), including seven who received immunosuppression (primarily glucocorticoids). During follow-up, 86% had stable/improved kidney function and 45% achieved complete while 15% achieved partial remission. Among the 15 patients with isolated sMGN without full nephrotic syndrome, only two received immunosuppression; nonetheless, 50% achieved complete while 21% achieved partial remission. Thus, sMGN is a rare PLA2R-negative variant of MGN with 29% NELL-1 positivity and favorable prognosis, even in the absence of immunosuppressive treatment.
Published: 2021

15. Epidemiology of Histologically Proven Glomerulonephritis in Africa: A Systematic Review and Meta-Analysis.

Author: Ikechi G Okpechi, Oluwatoyin I Ameh, Aminu K Bello, Pierre Ronco, Charles R Swanepoel, and Andre P Kengne
Subjects: Medicine, Science
Abstract: BACKGROUND AND AIM:Glomerulonephritis (GN) is a leading cause of end-stage renal disease (ESRD) in Africa. Data on epidemiology and outcomes of glomerular diseases from Africa is still limited. We conducted a systematic review on the epidemiology of histologically proven glomerular diseases in Africa between 1980 and 2014. MATERIALS AND METHODS:We searched literature using PubMed, AfricaWide, the Cumulative Index to Nursing and Allied Health Literature on EBSCO Host, Scopus, African Journals online databases, and the African Index Medicus, for relevant studies. The review was conducted using standard methods and frameworks using only biopsy-confirmed data. RESULTS:Twenty four (24) studies comprising 12,093 reported biopsies from 13 countries were included in this analysis. The median number of biopsies per study was 127.0 (50-4436), most of the studies (70.0%) originated from North Africa and the number of performed kidney biopsies varied from 5.2 to 617 biopsies/year. Nephrotic syndrome was the commonest indication of renal biopsy. The frequency of reported primary pathologic patterns included, minimal change disease (MCD); 16.5% (95%CI: 11.2-22.6), focal segmental glomerulosclerosis (FSGS); 15.9% (11.3-21.1), mesangiocapillary GN (MCGN); 11.8% (9.2-14.6), crescentic GN; 2.0% (0.9-3.5) and IgA nephropathy 2.8% (1.3-4.9). Glomerular diseases related to hepatitis B and systemic lupus erythematosus had the highest prevalence among assessed secondary diseases: 8.4% (2.0-18.4) and 7.7% (4.5-11.7) respectively. There was no evidence of publication bias and regional differences were seen mostly for secondary GNs. CONCLUSIONS:Glomerular diseases remain poorly characterized in sub-Saharan Africa due to declining renal biopsy rates and consequent paucity of data on pathologic patterns of key renal diseases. Development of renal biopsy registries in Africa is likely to enable adequate characterization of the prevalence and patterns of glomerular diseases; this could have a positive impact on chronic kidney disease evaluation and treatment in the African continent since most glomerulopathies are amenable to treatment.
Published: 2016
Full Text: View/download PDF

16. Semaphorin 3B–associated membranous nephropathy is a distinct type of disease predominantly present in pediatric patients

Author: David Buob, Hanna Debiec, Francesco Emma, Cheryl L. Tran, Fernando C. Fervenza, M. Cristine Charlesworth, Aishwarya Ravindran, Tim Ulinski, Benjamin J. Madden, Francesca Diomedi-Camassei, Sanjeev Sethi, Marina Vivarelli, Pierre Ronco, and Lou Ann Gross
Subjects: 0301 basic medicine, Immunoglobulin A, Pathology, medicine.medical_specialty, 030232 urology & nephrology, Semaphorins, Glomerulonephritis, Membranous, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Semaphorin, Glomerular Basement Membrane, Biopsy, Humans, Medicine, Child, Frozen section procedure, Membrane Glycoproteins, Microscopy, Confocal, biology, medicine.diagnostic_test, business.industry, Glomerular basement membrane, medicine.disease, Immunohistochemistry, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, Nephrology, Immunoglobulin M, biology.protein, business
Abstract: Membranous nephropathy results from subepithelial antigen-antibody complex deposition along the glomerular basement membrane. Although PLA2R, THSD7A, and NELL-1 account for a majority (about 80%) of the target antigens, the target antigen in the remaining cases is not known. Using laser microdissection of PLA2R-negative glomeruli of patients with membranous nephropathy followed by mass spectrometry we identified a unique protein, Semaphorin 3B, in three cases. Mass spectrometry failed to detect Semaphorin-3B in 23 PLA2R-associated cases of membranous nephropathy and 88 controls. Semaphorin 3B in all three cases was localized to granular deposits along the glomerular basement membrane by immunohistochemistry. Next, an additional eight cases of Semaphorin 3B-associated membranous nephropathy were identified in three validation cohorts by immunofluorescence microscopy. In four of 11 cases, kidney biopsy also showed tubular basement membrane deposits of IgG on frozen sections. Confocal microscopy showed that both IgG and Semaphorin 3B co-localized to the glomerular basement membrane. Western blot analysis of five available sera showed reactivity to reduced Semaphorin 3B in four of four patients with active disease and no reactivity in one patient in clinical remission; there was also no reactivity in control sera. Eight of the 11 cases of Semaphorin 3B-associated membranous nephropathy were pediatric cases. Furthermore, in five cases, the disease started at or below the age of two. Thus, Semaphorin 3B-associated membranous nephropathy appears to be a distinct type of disease; more likely to be present in pediatric patients.
Published: 2020

17. Nomenclature for kidney function and disease: report of a Kidney Disease

Author: Caroline Vinck, Andrew S. Levey, Mark Lambie, Josephine P. Briggs, Andrew Davenport, Susan J. Allison, Stacy L. Christiansen, Shari E. Leventhal, Stephen B. Walsh, Joseph Laycock, Jonathan S. Bromberg, Paul M. Palevsky, Denis Fouque, Brenda R. Hemmelgarn, Jennifer St. Clair Russell, Lesley A. Inker, Pascale H. Lane, Michael Cheung, Rajnish Mehrotra, Detlef Bockenhauer, Adeera Levin, Matthias Kretzler, Mark A. Perazella, Ron T. Gansevoort, Kai-Uwe Eckardt, Lesley Rees, Daniel E. Weiner, John S. Gill, Harold I. Feldman, Julie R. Ingelfinger, Allison Tong, Michael Mittelman, Michel Jadoul, Pierre Ronco, Nijsje M. Dorman, Marlies Ostermann, Patricia Morrissey, Wolfgang C. Winkelmayer, Franz Schaefer, Eddie L. Greene, Ewout J. Hoorn, School of Metallurgy and Materials, University of Birmingham [Birmingham], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), California Institute of Technology (CALTECH), 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), Sorbonne Université (SU), UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), and Internal Medicine
Subjects: 0301 basic medicine, medicine.medical_specialty, Glossary, kidney disease, precision medicine, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Renal function, Disease, Q1, 03 medical and health sciences, 0302 clinical medicine, kidney measures, medicine, patient-centeredness, Intensive care medicine, kidney function, Kidney, acute kidney diseases and disorders, business.industry, urogenital system, Acute kidney injury, Precision medicine, medicine.disease, R1, 3. Good health, kidney failure, 030104 developmental biology, medicine.anatomical_structure, acute kidney injury, Nephrology, Albuminuria, nomenclature, medicine.symptom, business, chronic kidney disease, Kidney disease
Abstract: The worldwide burden of kidney disease is rising, but public awareness remains limited, underscoring the need for more effective communication by stakeholders in the kidney health community. Despite this need for clarity, the nomenclature for describing kidney function and disease lacks uniformity. In June 2019, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Consensus Conference with the goal of standardizing and refining the nomenclature used in the English language to describe kidney function and disease, and of developing a glossary that could be used in scientific publications. Guiding principles of the conference were that the revised nomenclature should be patient-centered, precise, and consistent with nomenclature used in the KDIGO guidelines. Conference attendees reached general consensus on the following recommendations: (i) to use "kidney" rather than "renal" or "nephro-" when referring to kidney disease and kidney function; (ii) to use "kidney failure" with appropriate descriptions of presence or absence of symptoms, signs, and treatment, rather than "end-stage kidney disease"; (iii) to use the KDIGO definition and classification of acute kidney diseases and disorders (AKD) and acute kidney injury (AKI), rather than alternative descriptions, to define and classify severity of AKD and AKI; (iv) to use the KDIGO definition and classification of chronic kidney disease (CKD) rather than alternative descriptions to define and classify severity of CKD; and (v) to use specific kidney measures, such as albuminuria or decreased glomerular filtration rate (GFR), rather than "abnormal" or "reduced" kidney function to describe alterations in kidney structure and function. A proposed 5-part glossary contains specific items for which there was general agreement. Conference attendees acknowledged limitations of the recommendations and glossary, but they considered standardization of scientific nomenclature to be essential for improving communication.
Published: 2020

18. Nanometric Chemical Speciation of Abnormal Deposits in Kidney Biopsy: Infrared-Nanospectroscopy Reveals Heterogeneities within Vancomycin Casts

Author: Laurent Mesnard, Ariane Deniset-Besseau, Yosu Luque, Dominique Bazin, Alexandre Dazzi, Emmanuel Esteve, Michel Daudon, Pierre Ronco, Jehan Waeytens, Chantal Jouanneau, Laboratoire de Chimie-Physique (LCP), and Université de Cocody
Subjects: Chemical imaging, Spectrophotometry, Infrared, Infrared, Biopsy, Chimie analytique, Infrared spectroscopy, 010402 general chemistry, 01 natural sciences, Analytical Chemistry, Nuclear magnetic resonance, Vancomycin, medicine, Humans, [CHIM]Chemical Sciences, Molecule, ComputingMilieux_MISCELLANEOUS, medicine.diagnostic_test, Chemical speciation, Chemistry, 010401 analytical chemistry, Resolution (electron density), Médecine pathologie humaine, 0104 chemical sciences, Tubule, Microscopy, Electron, Scanning, Nanoparticles, Kidney Diseases, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Infrared (IR) spectromicroscopy allows chemical mapping of a kidney biopsy. It is particularly interesting for chemical speciation of abnormal tubular deposits and calcification. In 2017, using IR spectromicroscopy, we described a new entity called vancomycin cast nephropathy. However, despite recent progresses, the IR microspectrometer spatial resolution is intrinsically limited by diffraction (a few micrometers). Combining atomic force microscopy and IR lasers (AFMIR) allows acquisition of infrared absorption spectra with a resolution and sensitivity in between 10 and 100 nm. Here we show that AFMIR can be used on standard paraffin embedded kidney biopsies. Vancomycin cast could be identified in a damaged tubule. Interestingly unlike standard IR spectromicroscopy, AFMIR revealed heterogeneity of the deposits and established that vancomycin coprecipitated with phosphate containing molecules. These findings highlight the high potential of this approach with nanometric spatial resolution which opens new perspectives for studies on drug-induced nephritis, nanocrystals, and local lipid or carbohydrates alterations.
Published: 2020

19. Proteomic Analysis of Complement Proteins in Membranous Nephropathy

Author: Hanna Debiec, Daniel C. Cattran, Richard J.H. Smith, Benjamin J. Madden, Aishwarya Ravindran, Sanjeev Sethi, Amit Sethi, Rishi Sharma, M. Cristine Charlesworth, Fernando C. Fervenza, and Pierre Ronco
Subjects: Clusterin, biology, business.industry, 030232 urology & nephrology, CD59, 030204 cardiovascular system & hematology, medicine.disease, Proteomics, lcsh:Diseases of the genitourinary system. Urology, lcsh:RC870-923, Molecular biology, Complement system, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Nephrology, medicine, biology.protein, Alternative complement pathway, Properdin, Vitronectin, business
Abstract: Introduction: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in Caucasian adults. Phospholipase A2 receptor (PLA2R)– and exostosin 1 (EXT1)/exostosin 2 (EXT2)–associated MN represent the most common primary and secondary forms of MN. The complement profile using a proteomics approach has not been studied in these 2 common forms of MN. Methods: We used laser microdissection and mass spectrometry (MS/MS) to dissect glomeruli and identify glomerular complement proteins in PLA2R-associated (n = 7), EXT1/EXT2-associated MN (n = 21), and 11 control cases (time 0 transplant biopsies). Results: MS/MS identified high total spectral counts for PLA2R and EXT1/EXT2 in corresponding cases of PLA2R- and EXT1/EXT2-positive MN. Both PLA2R- and EXT1/EXT2-associated MN had high spectral counts of complement proteins C3, C4, C5, C6, C7, C8, and C9. Complement protein C1 was present in low spectral counts in EXT1/EXT2-associated MN. Regulators of complement activation that were detected in MN included higher spectral counts of FH, FHR-1, FHR-5, clusterin, vitronectin and lower spectral counts of FHR-3, FHR-4, and CD59. Low spectral counts of FB and properdin, key components of the alternative pathway, also were detected. IgG4 and IgG1 were the most abundant IgG subclasses in PLA2R- and EXT1/EXT2-associated MN. Lower spectral counts for C3, C4, and C5 were detected in control cases when compared with MN. Conclusion: Significant complement activation is present in MN as evidenced by large spectral counts of complement proteins from C3- and C4-based pathways, including regulatory proteins of complement pathways. These data suggest that anticomplement drugs may be effective in treatment for MN. Keywords: complement, laser microdissection, mass spectrometry, membranous nephropathy
Published: 2020

20. Development of a Standardized Chemiluminescence Immunoassay for the Detection of Autoantibodies Against Human M-Type Phospholipase A2 Receptor in Primary Membranous Nephropathy

Author: Iva Gunnarsson, Hanna Debiec, Cornelia Dähnrich, Sandra Saschenbrecker, Wolfgang Schlumberger, Pierre Ronco, Karolinska Institutet [Stockholm], Karolinska University Hospital [Stockholm], 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, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: anti-PLA2R, Chemiluminescence immunoassay, 030232 urology & nephrology, 030204 cardiovascular system & hematology, lcsh:RC870-923, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, law.invention, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Clinical Research, law, parasitic diseases, medicine, Indirect immunofluorescence, phospholipase A2 receptor, business.industry, Antibody titer, Autoantibody, membranous nephropathy, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, Molecular biology, 3. Good health, chemiluminescence immunoassay, Fully automated, Nephrology, Recombinant DNA, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, Phospholipase A2 receptor, autoantibody
Abstract: Introduction Autoantibodies against the M-type phospholipase A2 receptor (PLA2R) are important markers in the diagnosis and monitoring of primary membranous nephropathy (pMN). For the detection of anti-PLA2R autoantibodies, a standardized recombinant cell-based indirect immunofluorescence assay (RC-IFA) and enzyme-linked immunosorbent assay (ELISA) are widely used, the former providing higher sensitivity but lacking a finely graduated quantification of antibody titers. In this study, we evaluated the diagnostic performance characteristics of a novel standardized chemiluminescence immunoassay (ChLIA) by comparison with the established anti-PLA2R test systems. Methods Sera from 155 patients with biopsy-proven pMN and 154 disease controls were analyzed for autoantibodies against PLA2R by the novel ChLIA as well as by ELISA and RC-IFA. Results The clinical sensitivity of the ChLIA (83.9%) was higher compared with ELISA (73.5%) and equaled that of RC-IFA (83.2%), at similar specificities (≥99.4%). Among ELISA-negative pMN samples, ChLIA and RC-IFA yielded positive results in 39.0% and 36.6%, respectively. The qualitative agreement amounted to 94.5% (ChLIA vs. ELISA) and 99.4% (ChLIA vs. RC-IFA). Conclusion The novel anti-PLA2R ChLIA outperforms the ELISA in detecting patients with pMN and demonstrates almost perfect agreement with RC-IFA. It thus presents a promising alternative tool for accurate anti-PLA2R testing, with the advantage of rapid turnaround times and fully automated random-access processing., Graphical abstract
Published: 2020

21. KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases

Author: Carla M. Nester, Adrian Liew, Jürgen Floege, Elizabeth M. Rave, Sharon G. Adler, Kelly A. Burdge, Richard J. Glassock, Sydney C.W. Tang, Vivekanand Jha, Brad H. Rovin, Pierre Ronco, Jai Radhakrishnan, Jan-Stephan F. Sanders, Jonathan Barratt, Yusuke Suzuki, David Jayne, Sanjeev Sethi, Zhihong Liu, Juan M. Mejia-Vilet, Keisha L. Gibson, Heather N. Reich, Fernando C. Fervenza, Tak Mao Chan, Marina Vivarelli, H. Terence Cook, Vladimir Tesar, Jack F.M. Wetzels, Frank Bridoux, Apollo - University of Cambridge Repository, Rovin, Brad H., Adler, Sharon G., Jayne, David R. W., Jha, Vivekanand, Liew, Adrian, Liu, Zhi-Hong, Mejía-Vilet, Juan Manuel, Nester, Carla M., Radhakrishnan, Jai, Rave, Elizabeth M., Reich, Heather N., Ronco, Pierre, Barratt, Jonathan, Sanders, Jan-Stephan F., Sethi, Sanjeev, Suzuki, Yusuke, Tang, Sydney C. W., Tesar, Vladimir, Vivarelli, Marina, Wetzels, Jack F. M., Floege, Jürgen, Bridoux, Frank, Burdge, Kelly A., Chan, Tak Mao, Cook, H. Terence, Fervenza, Fernando C., Gibson, Keisha L., and Glassock, Richard J.
Subjects: medicine.medical_specialty, business.industry, 1103 Clinical Sciences, Guideline, Urology & Nephrology, Clinical Practice, Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group, Nephrology, Medicine, Humans, Kidney Diseases, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], Renal Insufficiency, Chronic, business, Intensive care medicine, Glomerular diseases, Glomerular Filtration Rate
Abstract: Kidney international 100(4, Supplement) S1-S276 (2021). doi:10.1016/j.kint.2021.05.021 special issue: "KDIGO 2021 Clinical Practice Guideline for the Management of Glomerular Diseases", Published by Elsevier, New York, NY
Published: 2021
Full Text: View/download PDF

22. Antenatal Membranous Nephropathy and Type 2 (Axonal) Charcot-Marie-Tooth With Mutations in the Metallo-Membrane Endopeptidase Gene: A Call for Family Screening and Pharmacovigilance

Author: Hanna Debiec, Gauthier Remiche, Marina Vivarelli, Nicolette C. Notermans, Jeroen Nauta, Guilhem Solé, Paul Delrée, Pierre Ronco, Joëlle Nortier, Daria Diodato, Pediatrics, Centre Hospitalier Universitaire Brugmann [Bruxelles] (CHU), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Eramus MC-Sophia Children’s Hospital, Partenaires INRAE, University Medical Center [Utrecht], Bambino Gesù Children’s Hospital [Rome, Italy], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gestionnaire, HAL Sorbonne Université 5
Subjects: peripheral neuropathy, Pharmacology, neprilysin, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Pharmacovigilance, Research Letter, medicine, 030212 general & internal medicine, Neprilysin, Gene, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, maternofetal allo-immunization, MME gene, membranous nephropathy, Généralités, medicine.disease, congenital nephropathy, neutral endopeptidase, Endopeptidase, 3. Good health, Peripheral neuropathy, Nephrology, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2021

23. High-Dose Rituximab and Early Remission in PLA2R1-Related Membranous Nephropathy

Author: Hanna Debiec, Christelle Zaghrini, Alessandra Rosenthal, Michel Ticchioni, Karine Dahan, Gérard Lambeau, Alexandra Rousseau, Barbara Seitz-Polski, Vincent L.M. Esnault, Marine Andreani, Ghislaine Bernard, Pierre Ronco, Sylvia Benzaken, Departement d'immunologie, hôpital de l'Archet, CHU de Nice, Département de Néphrologie - Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), 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), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d'Immunologie, Centre Hospitalier Universitaire de Nice (CHU de Nice)-Groupe hospitalier l'Archet (Nice), Laboratoire Immunologie [Nice], Hôpital de l'Archet-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)
Subjects: Male, medicine.medical_specialty, Epidemiology, 030232 urology & nephrology, Nice, Early remission, Critical Care and Intensive Care Medicine, Glomerulonephritis, Membranous, Gastroenterology, Cohort Studies, Epitopes, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Interquartile range, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, medicine, Immunologic Factors, Humans, Prospective Studies, ComputingMilieux_MISCELLANEOUS, Aged, 030304 developmental biology, computer.programming_language, Epitope spreading, 0303 health sciences, Transplantation, business.industry, Receptors, Phospholipase A2, Remission Induction, Editorials, Original Articles, Middle Aged, 16. Peace & justice, medicine.disease, 3. Good health, Nephrology, Cohort, Female, Rituximab, business, computer, medicine.drug, Cohort study
Abstract: BACKGROUND AND OBJECTIVES: Different rituximab protocols are used to treat membranous nephropathy. We compared two rituximab protocols in patients with membranous nephropathy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Twenty-eight participants from the NICE cohort received two infusions of 1-g rituximab at 2-week intervals, whereas 27 participants from the Prospective Randomized Multicentric Open Label Study to Evaluate Rituximab Treatment for Membranous Nephropathy (GEMRITUX) cohort received two infusions of 375 mg/m(2) at 1-week interval. We measured serum rituximab levels and compared remission at month 6 and before any treatment modification and analyzed factors associated with remission and relapses. RESULTS: Remissions occurred in 18 (64%) versus eight (30%) from the NICE and GEMRITUX cohort (P=0.02) at month 6, respectively, and in 24 (86%) versus 18 (67%) participants (P=0.12) before treatment modification, respectively. Median time to remission was 3 [interquartile range (IQR), 3–9] and 9 [IQR, 6–12] months for NICE and GEMRITUX cohorts respectively (P=0.01). Participants from the NICE cohort had higher circulating level of rituximab and lower CD19 counts (3.3 µg/L [IQR, 0.0–10.8] versus 0.0 [IQR, 0.0–0.0] P
Published: 2019

24. Prevalence of tubulopathy and association with renal function loss in HIV-infected patients

Author: Emmanuelle Plaisier, Marie-Gisèle Lebrette, Pierre Ronco, Emmanuel Esteve, Jacqueline Capeau, J.-B. Guiard-Schmid, Soraya Fellahi, Anne-Line Eme, Gilles Pialoux, François-Xavier Lescure, Dominique Costagliola, Jean-Philippe Bastard, Service des Maladies Infectieuses et Tropicales [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Nord, Université Paris Diderot - Paris 7 (UPD7), Université Sorbonne Paris Cité (USPC), Service de biochimie et hormonologie [CHU Tenon], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Sorbonne Université (SU), Service des maladies infectieuses et tropicales [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP]-Sorbonne Université (SU), Service de Néphrologie et Dialyses [CHU Tenon], Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), 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), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, microalbuminuria, Anti-HIV Agents, Population, proximal tubule dysfunction, 030232 urology & nephrology, Renal function, HIV Infections, urologic and male genital diseases, GFR, 03 medical and health sciences, 0302 clinical medicine, Tubulopathy, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, Prevalence, medicine, Humans, Prospective Studies, Renal Insufficiency, Chronic, Tenofovir, 10. No inequality, education, Transplantation, education.field_of_study, Proteinuria, business.industry, Incidence (epidemiology), Editorials, HIV, Odds ratio, Middle Aged, medicine.disease, 030112 virology, 3. Good health, Kidney Tubules, Nephrology, ethnicity, Female, Microalbuminuria, France, medicine.symptom, business, Biomarkers, Glomerular Filtration Rate, Kidney disease
Abstract: Background The incidence of chronic kidney disease (CKD) is 10 times higher in human immunodeficiency virus (HIV)-infected patients than in the general population. We explored the prevalence and determinants of proximal tubular dysfunction (PTD) in HIV-infected individuals, and assessed the impact of the tubulopathy on the estimated glomerular filtration rate (eGFR) outcome. Methods A cohort study was performed on 694 outpatients followed in a French centre to analyse the prevalence of PTD, the diagnosis performance of screening tools and the associated factors. eGFR was prospectively evaluated to analyse the predictive value of the tubulopathy on eGFR decrease. Results At inclusion, 14% of the patients presented with PTD and 5% with CKD. No individual tubular marker, including non-glomerular proteinuria, glycosuria dipstick or hypophosphataemia, registered sufficient performance to identify PTD. We found a significant interaction between tenofovir disoproxil fumarate exposure and ethnicity (P = 0.03) for tubulopathy risk. Tenofovir disoproxil fumarate exposure was associated with PTD in non-Africans [adjusted odds ratio (aOR) = 4.71, P Conclusion PTD is not rare in HIV-infected individuals but is less frequent in sub-Saharan African patients and is associated with tenofovir disoproxil fumarate exposure only in non-Africans. Its diagnosis requires multiple biochemical testing and it is not associated with an accelerated eGFR decline.
Published: 2019

25. Management and treatment of glomerular diseases (part 2): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Author: Brad H. Rovin, Dawn J. Caster, Daniel C. Cattran, Keisha L. Gibson, Jonathan J. Hogan, Marcus J. Moeller, Dario Roccatello, Michael Cheung, David C. Wheeler, Wolfgang C. Winkelmayer, Jürgen Floege, Sharon G. Adler, Charles E. Alpers, Isabelle Ayoub, Arvind Bagga, Sean J. Barbour, Jonathan Barratt, Daniel T.M. Chan, Anthony Chang, Jason Chon Jun Choo, H. Terence Cook, Rosanna Coppo, Fernando C. Fervenza, Agnes B. Fogo, Jonathan G. Fox, Richard J. Glassock, David Harris, Elisabeth M. Hodson, Elion Hoxha, Kunitoshi Iseki, J. Charles Jennette, Vivekanand Jha, David W. Johnson, Shinya Kaname, Ritsuko Katafuchi, A. Richard Kitching, Richard A. Lafayette, Philip K.T. Li, Adrian Liew, Jicheng Lv, Ana Malvar, Shoichi Maruyama, Juan Manuel Mejía-Vilet, Chi Chiu Mok, Patrick H. Nachman, Carla M. Nester, Eisei Noiri, Michelle M. O'Shaughnessy, Seza Özen, Samir M. Parikh, Hyeong-Cheon Park, Chen Au Peh, William F. Pendergraft, Matthew C. Pickering, Evangéline Pillebout, Jai Radhakrishnan, Manish Rathi, Pierre Ronco, William E. Smoyer, Sydney C.W. Tang, Vladimír Tesař, Joshua M. Thurman, Hernán Trimarchi, Marina Vivarelli, Giles D. Walters, Angela Yee-Moon Wang, Scott E. Wenderfer, Jack F.M. Wetzels, Baylor College of Medicine (BCM), Baylor University, Division of Nephrology, Rheinisch-Westfälische Technische Hochschule Aachen (RWTH), Department of Pediatrics, Division of Pediatric Nephrology and Genetics, All India Institute of Medical Sciences, University of British Columbia (UBC), Science of Turin Health Agency [Turin, Italy] (City of the Health), Regina Margherita University Children's Hospital [Turin, Italy], Mayo Clinic [Rochester], University College of London [London] (UCL), Molecular Otolaryngology and Renal Research Laboratories [Iowa City, IA, USA] (Carver College of Medicine), University of Iowa [Iowa City]-Carver College of Medicine, University of Iowa, Centre for Complement and Inflammation Research [London, UK] (Department of Medicine), Imperial College London, Service de rhumatologie, CHU Bordeaux [Bordeaux], CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Colorado [Denver], Department of Medicine, The University of Hong Kong (HKU), Department of Nephrology [Nijmegen, The Netherlands], and Radboud University Medical Centre [Nijmegen, The Netherlands]
Subjects: 0301 basic medicine, Nephrology, medicine.medical_specialty, membranoproliferative glomerulonephritis, Consensus Development Conferences as Topic, 030232 urology & nephrology, Lupus nephritis, Paraproteinemias, Context (language use), Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, anti-neutrophil cytoplasmic antibody–associated vasculitis, 03 medical and health sciences, 0302 clinical medicine, Glomerulonephritis, Risk Factors, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, Membranoproliferative glomerulonephritis, medicine, Humans, Minimal change disease, C3 glomerulopathy, Genetic Testing, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, KDIGO, lupus nephritis, business.industry, Podocytes, Nephrosis, Lipoid, monoclonal gammopathies of renal significance, Guideline, medicine.disease, focal and segmental glomerulosclerosis, 3. Good health, minimal change disease, 030104 developmental biology, Treatment Outcome, Practice Guidelines as Topic, Disease Progression, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, Biomarkers, Kidney disease, Glomerular Filtration Rate
Abstract: Contains fulltext : 203024.pdf (Publisher’s version ) (Open Access) In November 2017, the Kidney Disease: Improving Global Outcomes (KDIGO) initiative brought a diverse panel of experts in glomerular diseases together to discuss the 2012 KDIGO glomerulonephritis guideline in the context of new developments and insights that had occurred over the years since its publication. During this KDIGO Controversies Conference on Glomerular Diseases, the group examined data on disease pathogenesis, biomarkers, and treatments to identify areas of consensus and areas of controversy. This report summarizes the discussions on primary podocytopathies, lupus nephritis, anti-neutrophil cytoplasmic antibody-associated nephritis, complement-mediated kidney diseases, and monoclonal gammopathies of renal significance.
Published: 2019

26. Protocadherin 7-Associated Membranous Nephropathy

Author: Vivian Negron, Sanjeev Sethi, Hanna Debiec, Michel Jadoul, Lou Ann Gross, Benjamin J. Madden, David Buob, M. Cristine Charlesworth, Pierre Ronco, Sidharth Chaudhry, Johann Morelle, Fernando C. Fervenza, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, and UCL - (SLuc) Service de néphrologie
Subjects: Adult, Male, Pathology, medicine.medical_specialty, glomerular disease, Laser Capture Microdissection, Immunofluorescence, Glomerulonephritis, Membranous, Mass Spectrometry, Cohort Studies, Membranous nephropathy, Western blot, renal biopsy, Clinical Research, renal pathology, Biopsy, medicine, Humans, Aged, Microscopy, Confocal, medicine.diagnostic_test, Chemistry, nephrotic syndrome, Glomerular basement membrane, membranous nephropathy, General Medicine, Middle Aged, medicine.disease, Cadherins, Protocadherins, Staining, medicine.anatomical_structure, Nephrology, immunology and pathology, Case-Control Studies, Immunohistochemistry, Female, Renal biopsy
Abstract: Background Membranous nephropathy (MN) results from deposition of antigen-antibody complexes along the glomerular basement membrane (GBM). PLA2R, THSD7A, NELL1, and SEMA3B account for 80%-90% of target antigens in MN. Methods We performed laser microdissection and mass spectrometry (MS/MS) in kidney biopsies from 135 individuals with PLA2R-negative MN, and used immunohistochemistry/immunofluorescence and confocal microscopy to confirm the MS/MS finding, detect additional cases, and localize the novel protein. We also performed MS/MS and immunohistochemistry on 116 controls and used immunofluorescence microscopy to screen biopsy samples from two validation cohorts. Western blot and elution studies were performed to detect antibodies in serum and biopsy tissue. Results MS/MS studies detected a unique protein, protocadherin 7 (PCDH7), in glomeruli of ten (5.7%) PLA2R-negative MN cases, which also were negative for PLA2R, THSD7A, EXT1/EXT2, NELL1, and SEMA3B. Spectral counts ranged from six to 24 (average 13.2 [SD 6.6]). MS/MS did not detect PCDH7 in controls (which included 28 PLA2R-positive cases). In all ten PCDH7-positive cases, immunohistochemistry showed bright granular staining along the GBM, which was absent in the remaining cases of PLA2R-negative MN and control cases. Four of 69 (5.8%) cases in the validation cohorts (all of which were negative for PLA2R, THSD7A, EXT1, NELL1, and SEMA3B) were PCDH7-positive MN. Kidney biopsy showed minimal complement deposition in 12 of the 14 PCDH7-associated cases. Confocal microscopy showed colocalization of PCDH7 and IgG along the GBM. Western blot analysis using sera from six patients showed antibodies to nonreduced PCDH7. Elution of IgG from frozen tissue of PCDH7-associated MN showed reactivity against PCDH7. Conclusions MN associated with the protocadherin PCDH7 appears to be a distinct, previously unidentified type of MN.
Published: 2021

27. Diagnostic performance of glomerular PLA2R and THSD7A antibodies in biopsy confirmed primary membranous nephropathy in South Africans

Author: Ugochi S. Okpechi-Samuel, Pierre Ronco, Nicola Wearne, Ikechi G. Okpechi, Aminu K. Bello, Francois Cj Botha, Oluwatoyin I. Ameh, Bingileki F Lwezaula, and Udeme E. Ekrikpo
Subjects: Nephrology, Adult, Male, medicine.medical_specialty, PLA2R, Kidney Glomerulus, 030232 urology & nephrology, Lupus nephritis, 030204 cardiovascular system & hematology, lcsh:RC870-923, Gastroenterology, Glomerulonephritis, Membranous, Primary membranous nephropathy, Diabetic nephropathy, 03 medical and health sciences, South Africa, 0302 clinical medicine, Membranous nephropathy, Internal medicine, Biopsy, medicine, Humans, Autoantibodies, biology, medicine.diagnostic_test, business.industry, Receptors, Phospholipase A2, Histology, Middle Aged, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, Cross-Sectional Studies, THSD7A, biology.protein, Immunohistochemistry, Female, Antibody, business, Thrombospondins, Research Article, Africans
Abstract: Background: Serum and tissue-based tests using phospholipase A2 receptor 1 (PLA2R) and thrombospondin type-1 domain containing 7A (THSD7A) are established immune biomarkers for the diagnosis of primary membranous nephropathy (PMN). This study assessed the diagnostic performance of these biomarkers in the diagnosis of PMN in South Africans. Methods This was a cross-sectional analysis from a single centre in Cape Town, South Africa. Relevant biodata was collected from all patients. Histology, including slides for PLA2R and THSD7A were processed and assessed by typical microscopic and immunohistochemical features. Biopsy tissues of patients with membranous lupus nephritis (LN-V) and diabetic nephropathy (DN) were used as controls. The diagnostic accuracy for diagnosis of PMN using positive PLA2R and THSD7A were evaluated. Results Of the 88 patients included, 41 had PMN with a mean age of 44.5 ± 17.5 years and 61.0% were female. Histologically, PLA2R and THSD7A were only positive in the PMN group (51.2% and 4.9%, respectively) but negative in both control groups. The sensitivity of PLA2R and THSD7A for identifying PMN was 51.2% and 4.9%, respectively. The sensitivity of both tests together was 53.7% while the specificity and positive predictive values (PPV) for any of the tests (alone or in combination) was 100%. There was no difference in the sensitivity and specificity when using PLA2R alone compared to combining the two tests (p=0.32). Conclusion Glomerular staining of PLA2R and THSD7A could have potential diagnostic values in South Africans. This has implications on how immunotherapies can be initiated and used in these settings.
Published: 2021

28. Transcription factor 21 expression in injured podocytes of glomerular diseases

Author: Mayumi Takahashi-Kobayashi, Satoshi Yamazaki, Joichi Usui, Kunihiro Yamagata, Pierre Ronco, Surya V. Seshan, Shuzo Kaneko, Tetsuya Kawamura, Misa Yaguchi, Université de Tsukuba = University of Tsukuba, Weill Medical College of Cornell University [New York], Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Nephrotic Syndrome, Urinary system, [SDV]Life Sciences [q-bio], Kidney Glomerulus, 030232 urology & nephrology, lcsh:Medicine, Kidney development, Biology, Severity of Illness Index, Article, Podocyte, 03 medical and health sciences, Mice, 0302 clinical medicine, Internal medicine, medicine, Basic Helix-Loop-Helix Transcription Factors, Animals, Humans, lcsh:Science, Urinary Tract, Transcription factor, Multidisciplinary, Kidney diseases, Podocytes, lcsh:R, Middle Aged, medicine.disease, Actin cytoskeleton, Rats, [SDV] Life Sciences [q-bio], Actin Cytoskeleton, Disease Models, Animal, Proteinuria, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Cell culture, Apoptosis, Nephrology, lcsh:Q, Female, Nephrotic syndrome
Abstract: Transcription factor 21 (TCF21) is one of the essential transcription factors in kidney development. To elucidate its influence on glomerular disease, we have investigated TCF21 expression in human and rat kidney tissue, and its urinary concentration. Immunohistological analysis suggested the highest TCF21 expression in nephrotic syndrome along with the urinary protein level. Urinary TCF21 concentration in human showed a positive correlation with its podocyte expression level. In nephrotic rat models, TCF21 expression in podocytes increased along with the severity of nephrotic syndrome. Next, in vitro experiments using Tcf21-expressing murine podocyte cell line, we could observe some Tcf21-dependent effects, related with actin cytoskeleton dysregulation and apoptosis. Our study illustrated TCF21 expression changes in vivo and its in vitro-functional significance injured podocytes.
Published: 2020

29. The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis

Author: Taner Basturk, Ali G. Gharavi, Patrick Hamilton, Nan Chen, Kai-Uwe Eckardt, Weiming Wang, Paul Brenchley, Olivia Balderes, Dong Ki Kim, Elisabet Ars, Antonio Amoroso, Mehmet Sukru Sever, Neil Ashman, Bartosz Foroncewicz, Dan Zhang, Maddalena Marasa, Francesca Lugani, Elion Hoxha, Mario Bonomini, Gang Liu, Detlef Bockenhauer, Hakki Arikan, Pietro A. Canetta, Bruno Vogt, Magdalena Durlik, Carlo Sidore, Abdulmecit Yildiz, Mehmet Koc, Magdalena Zoledziewska, Simone Sanna-Cherchi, Antonello Pani, Domenico Santoro, Francesca Zanoni, Landino Allegri, Matthias Kretzler, Ireneusz Habura, Claudia Izzi, Naomi Issler, Carmelita Marcantoni, Isabella Pisani, Monica Bodria, Hajeong Lee, Krzysztof Mucha, Ruth J. F. Loos, Lawrence H. Beck, Laura H. Mariani, Rolf A.K. Stahl, Eimear E. Kenny, Gonca E. Karahan, Pierre Ronco, Robert Kleta, Francesco Scolari, José Ballarín, Francesco Londrino, Bénédicte Stengel, Dario Roccatello, Atlas Khan, Belong Cho, Gerald B. Appel, Lili Liu, Xiaofan Hu, Savas Ozturk, Karla Mehl, Ming hui Zhao, Ruth J. Pepper, Shreeram Akilesh, Zhao Cui, Yifu Li, Anna Köttgen, Lambertus A. Kiemeney, Fatih Ozay, Jack F.M. Wetzels, Stephen H. Powis, Jun Zhang, Silvana Savoldi, Hong Ren, Matthias Wuttke, John O. Connolly, Yon Su Kim, Gianluigi Zaza, Chris Cheshire, Simona Granata, Andrew S. Bomback, Nurhan Seyahi, Donatella Spotti, Vladimir Tesar, Stephanie Dufek, Fernando C. Fervenza, Krzysztof Kiryluk, Barbara Moszczuk, Leszek Pączek, Agnieszka Perkowska-Ptasińska, Nikol Mladkova, Shelly Harris, Loreto Gesualdo, Hitoshi Suzuki, Jin Ho Park, Jana Reiterova, Julia M. Hofstra, Francesco Cucca, Li Lin, Laila Yasmin Mani, Sanjana Gupta, Ben Sprangers, Iuliana Ionita-Laza, Daniel C. Cattran, Gian Marco Ghiggeri, Sebahat Akgul, Horia Stanescu, Matthew G. Sampson, Piergiorgio Messa, Xialian Yu, Marieke J H Coenen, Hanna Debiec, Jingyuan Xie, Jing Xu, Yasar Caliskan, Raphael J. Rosen, Priya Krithivasan, Marco Galliani, Xie, Jingyuan, Liu, Lili, Mladkova, Nikol, Li, Yifu, Ren, Hong, Wang, Weiming, Cui, Zhao, Lin, Li, Hu, Xiaofan, Yu, Xialian, Xu, Jing, Liu, Gang, Caliskan, Yasar, Sidore, Carlo, Balderes, Olivia, Rosen, Raphael J., Bodria, Monica, Zanoni, Francesca, Zhang, Jun Y., Krithivasan, Priya, Mehl, Karla, Marasa, Maddalena, Khan, Atlas, Ozay, Fatih, Canetta, Pietro A., Bomback, Andrew S., Appel, Gerald B., Sanna-Cherchi, Simone, Sampson, Matthew G., Mariani, Laura H., Perkowska-Ptasinska, Agnieszka, Durlik, Magdalena, Mucha, Krzysztof, Moszczuk, Barbara, Foroncewicz, Bartosz, Paczek, Leszek, Habura, Ireneusz, Ars, Elisabet, Ballarin, Jose, Mani, Laila-Yasmin, Vogt, Bruno, Ozturk, Savas, Yildiz, Abdulmecit, Seyahi, Nurhan, Arikan, Hakki, Koc, Mehmet, Basturk, Taner, Karahan, Gonca, Akgul, Sebahat Usta, Sever, Mehmet Sukru, Zhang, Dan, Santoro, Domenico, Bonomini, Mario, Londrino, Francesco, Gesualdo, Loreto, Reiterova, Jana, Tesar, Vladimir, Izzi, Claudia, Savoldi, Silvana, Spotti, Donatella, Marcantoni, Carmelita, Messa, Piergiorgio, Galliani, Marco, Roccatello, Dario, Granata, Simona, Zaza, Gianluigi, Lugani, Francesca, Ghiggeri, GianMarco, Pisani, Isabella, Allegri, Landino, Sprangers, Ben, Park, Jin-Ho, Cho, BeLong, Kim, Yon Su, Kim, Dong Ki, Suzuki, Hitoshi, Amoroso, Antonio, Cattran, Daniel C., Fervenza, Fernando C., Pani, Antonello, Hamilton, Patrick, Harris, Shelly, Gupta, Sanjana, Cheshire, Chris, Dufek, Stephanie, Issler, Naomi, Pepper, Ruth J., Connolly, John, Powis, Stephen, Bockenhauer, Detlef, Stanescu, Horia C., Ashman, Neil, Loos, Ruth J. F., Kenny, Eimear E., Wuttke, Matthias, Eckardt, Kai-Uwe, Koettgen, Anna, Hofstra, Julia M., Coenen, Marieke J. H., Kiemeney, Lambertus A., Akilesh, Shreeram, Kretzler, Matthias, Beck, Lawrence H., Stengel, Benedicte, Debiec, Hanna, Ronco, Pierre, Wetzels, Jack F. M., Zoledziewska, Magdalena, Cucca, Francesco, Ionita-Laza, Iuliana, Lee, Hajeong, Hoxha, Elion, Stahl, Rolf A. K., Brenchley, Paul, Scolari, Francesco, Zhao, Ming-hui, Gharavi, Ali G., Kleta, Robert, Chen, Nan, Kiryluk, Krzysztof, İÜC, Cerrahpaşa Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Bursa Uludağ Üniversitesi/Tıp Fakültesi/Dahili Tıp Bilimleri., Yıldız, Abdülmecit, and GJU-0662-2022
Subjects: diagnosis, Phospholipase A2 receptor, Genome-wide association study, Gene, Glomerulonephritis, Membranous, DISEASE, membranous nephropahty, PLA2R1 protein, human, 0302 clinical medicine, Models, Phospholipase A2, Ethnicity, GWAS, genetics, Membranous Nephropathy, lcsh:Science, Diagnostic test accuracy study, RISK ALLELES, NFKB1 protein, human, 3. Good health, HLA, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], Cohort analysis, Testing method, Human, medicine.medical_specialty, Science, Immunology, European Continental Ancestry Group, Case control study, Single-nucleotide polymorphism, Locus (genetics), Major clinical study, Human leukocyte antigen, European, Article, General Biochemistry, Genetics and Molecular Biology, White People, 03 medical and health sciences, Membranous nephropathy, Asian People, Humans, Amino Acid Sequence, Polymorphism, GENOME-WIDE ASSOCIATION, Antibody, Alleles, METAANALYSIS, Ancestry, Autoimmune disease, Receptors, Phospholipase A2, Case-control study, Molecular, medicine.disease, 030104 developmental biology, Immunoglobulin enhancer binding protein, Case-Control Studies, lcsh:Q, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], MHC, 0301 basic medicine, Models, Molecular, Enzyme linked immunosorbent assay, PLA2R1 gene, genetics, membranous nephropahty, GWAS, HLA, NF-KAPPA-B, 030232 urology & nephrology, General Physics and Astronomy, Gene locus, ACTIVATION, Glomerulonephritis, Receptors, Membranous Nephropathy, genome-wide association study (GWAS), diagnosis, Interferon regulatory factor 4, East Asian, Allele, Multidisciplinary, Genetic analysis, Membrane, Single Nucleotide, Sensitivity and specificity, Interferon regulatory factor, Interferon Regulatory Factors, Asian Continental Ancestry Group, EXPRESSION, Detection method, HLA antigen, SUSCEPTIBILITY LOCI, 610 Medicine & health, Caucasian, Membranous, Polymorphism, Single Nucleotide, Multidisciplinary sciences, Molecular model, Non invasive measurement, Internal medicine, NF-kappa B p50 Subunit, Genome-Wide Association Study, medicine, Human tissue, Membranous glomerulonephritis, Genetic risk, Multifactorial Inheritance, Summary Statistic, Single Nucleotide Polymorphism, RECEPTOR, business.industry, General Chemistry, genome-wide association study (GWAS), Single nucleotide polymorphism, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], business, Controlled study, Meta analysis
Abstract: Vogt, Bruno/0000-0002-1548-6387; Dufek, Stephanie/0000-0002-6323-6673; Liu, Lili/0000-0002-2622-9669; Paczek, Leszek/0000-0003-0160-3009; Cui, Zhao/0000-0002-5837-1926; amoroso, antonio/0000-0002-9437-9407; Rosen, Raphael/0000-0003-1025-1965; Loos, Ruth/0000-0002-8532-5087; coenen, marieke/0000-0001-8796-2031; zanoni, francesca/0000-0001-9567-6713; CUCCA, Francesco/0000-0002-7414-1995; Ars, Elisabet/0000-0002-4118-4358; Hamilton, Patrick/0000-0001-6703-3745 WOS:000563559600001 PubMed ID: 32231244 Membranous Nephropathy (MN) is a rare autoimmune cause of kidney failure. Here we report a genome-wide association study (GWAS) for primary MN in 3,782 cases and 9,038 controls of East Asian and European ancestries. We discover two previously unreported loci, NFKB1 (rs230540, OR = 1.25, P = 3.4 x 10(-12)) and IRF4 (rs9405192, OR = 1.29, P = 1.4 x 10(-14)), fine-map the PLA2R1 locus (rs17831251, OR = 2.25, P = 4.7 x 10(-103)) and report ancestry-specific effects of three classical HLA alleles: DRB1*1501 in East Asians (OR = 3.81, P = 2.0 x 10(-49)), DQA1*0501 in Europeans (OR = 2.88, P = 5.7 x 10(-93)), and DRB1*0301 in both ethnicities (OR = 3.50, P = 9.2 x 10(-23) and OR = 3.39, P = 5.2 x 10(-82), respectively). GWAS loci explain 32% of disease risk in East Asians and 25% in Europeans, and correctly re-classify 20-37% of the cases in validation cohorts that are antibody-negative by the serum anti-PLA2R ELISA diagnostic test. Our findings highlight an unusual genetic architecture of MN, with four loci and their interactions accounting for nearly one-third of the disease risk. National Institute for Diabetes and Digestive Kidney Diseases (NIDDK) [RC2-DK116690, R01-DK105124, R01-DK097053, R01-DK108805]; National Institute on Minority Health and Health Disparities (NIMHD)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Minority Health & Health Disparities (NIMHD) [R01-MD009223]; Charles Woodson Clinical Research Fund; Nephrotic Syndrome Study Network Consortium (NEPTUNE) [U54-DK-083912]; Columbia University, Columbia Glomerular Center; Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS); National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK); University of MichiganUniversity of Michigan System; NephCure Kidney International; Halpin Foundation; National Key Research and Development Program of China [2016YFC0904100]; Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81621092]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81870460, 81570598]; Science and Technology Innovation Action Plan of Shanghai Science and Technology Committee [17441902200]; Shanghai Municipal Education Commission, Gaofeng, Clinical Medicine Grant [20152207]; Shanghai Jiao Tong University School of Medicine, Multi-Center Clinical Research Project [DLY201510]; International Cooperation and Exchange Projects of Shanghai Science and Technology Committee [14430721000]; Outstanding Young Scholar Award [81622009]; Shanghai Health and Family Planning Committee Hundred Talents Program [2018BR37]; Seoul National University Hospital Human Biobank, a member of the National Biobank of Korea - Ministry of Health and Welfare, Republic of Korea; MRCMedical Research Council UK (MRC) [MR/J010847/1]; Manchester Academic Health Science Centre [MAHSC 186/200]; Greater Manchester Local Clinical Research Network; Kidneys for Life Charity; David and Elaine Potter Charitable Foundation; St Peter's Trust for Kidney, Bladder and Prostate Research; Kids Kidney Research UKKidney Research UK (KRUK); Kidney Research UKKidney Research UK (KRUK); Italian Ministry of Health grantMinistry of Health, Italy [GR-2011-02350438]; Department of Excellence Grant 2018-2022 - Italian Ministry of Education for the Department of Medical Sciences of the University of Turin; Columbia University; Poznan University of Medical Sciences, Poland; German Ministry of Education and Research (BMBF)Federal Ministry of Education & Research (BMBF) [01ER0804]; KfH Foundation for Preventive Medicine; Bayer Pharma AG; German Research FoundationGerman Research Foundation (DFG) [CRC 1140, KO 3598/3-1, CRC 992]; European Research CouncilEuropean Research Council (ERC) [ERC-2012ADG_2012-0314, 322947]; 7th Framework Programme of the European Community contract [2012-305608]; National Research Agency grant MNaims [ANR-17-CE17-0012-01]; Dutch Kidney Foundation [OW08, KJPB11.021]; National Human Genome Research Institute (NHGRI)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Human Genome Research Institute (NHGRI); NIMHD We are grateful to all study participants across multiple nephrology centres worldwide for their contributions to this work. This work was supported by the following institutions, grants and funding agencies in the US: Columbia University, Columbia Glomerular Center, National Institute for Diabetes and Digestive Kidney Diseases (NIDDK) grants RC2-DK116690 (K.K., M.K.), R01-DK105124 (K.K.), R01-DK097053 (L.H.B., M.K.), R01-DK108805 (M.G.S.), and National Institute on Minority Health and Health Disparities (NIMHD) grant R01-MD009223 (K.K., A.G.G., A.B.). M.G.S. is additionally supported by the Charles Woodson Clinical Research Fund. The Nephrotic Syndrome Study Network Consortium (NEPTUNE), U54-DK-083912, is a part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN), supported through a collaboration between the Office of Rare Diseases Research, National Center for Advancing Translational Sciences (NCATS) and the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK). Additional funding and/or programmatic support for this project has also been provided by the University of Michigan, the NephCure Kidney International and the Halpin Foundation. The recruitment and analysis of the Chinese cohorts were supported by the National Key Research and Development Program of China (2016YFC0904100), Natural Science Foundation of China to the Innovation Research Group (81621092), National Natural Science Foundation of China (No. 81870460, 81570598), Science and Technology Innovation Action Plan of Shanghai Science and Technology Committee (No.17441902200), Shanghai Municipal Education Commission, Gaofeng, Clinical Medicine Grant (No.20152207), Shanghai Jiao Tong University School of Medicine, Multi-Center Clinical Research Project (No.DLY201510), International Cooperation and Exchange Projects of Shanghai Science and Technology Committee (No.14430721000), the Outstanding Young Scholar Award for Zhao Cui (No.81622009), and Shanghai Health and Family Planning Committee Hundred Talents Program for Jingyuan Xie (No.2018BR37). The recruitment of the Korean cohort was supported by the Seoul National University Hospital Human Biobank, a member of the National Biobank of Korea, financed by the Ministry of Health and Welfare, Republic of Korea. P.B. and P.H. acknowledge financial support from MRC project "Autoimmunity in Membranous Nephropathy", grant MR/J010847/1 which funded the sample collection from MN patients across the UK. P.B., P.H. and S.H. acknowledge support from Manchester Academic Health Science Centre (MAHSC 186/200), the Greater Manchester Local Clinical Research Network and Kidneys for Life Charity for supporting research in MN in Manchester. We are grateful to the MENTOR study (clinical trials no. NCT01180036), for contributing blood samples of trial participants. The UK cohort was supported in part by grants from the David and Elaine Potter Charitable Foundation (to S.H.P. and R.K.), St Peter's Trust for Kidney, Bladder and Prostate Research (to D.B., H.C.S., S.H.P. and R.K.), Kids Kidney Research UK and Kidney Research UK (to D.B. and R.K.). The Italian cohorts were supported by the Italian Ministry of Health grant GR-2011-02350438 (G.Z., S.G.) and the Department of Excellence Grant 2018-2022 funded by the Italian Ministry of Education for the Department of Medical Sciences of the University of Turin (A.A.).; The recruitment of Polish cases was sponsored by the Polish Kidney Genetics Network (POLYGENES), a collaborative effort between Columbia University and Poznan University of Medical Sciences, Poland. The full list of POLYGENES collaborators can be found in the Supplementary Materials. The GCKD (German Chronic Kidney Disease) study was funded by grants from the German Ministry of Education and Research (BMBF, No. 01ER0804) and the KfH Foundation for Preventive Medicine, with genotyping supported by Bayer Pharma AG. The list of GCKD investigators can be found in the Supplementary Materials. The work of M.W. and A.K. was funded by the CRC 1140 Initiative and by KO 3598/3-1 and CRC 992 (A.K.) of the German Research Foundation. The work of E.H. and R.A.K.S. was funded by the CRC 1192 from the German Research Foundation (Projects B1 and C1). P.R. is a recipient of European Research Council ERC-2012ADG_2012-0314 grant 322947, 7th Framework Programme of the European Community contract 2012-305608 (European Consortium for High-Throughput Research in Rare Kidney Diseases), and the National Research Agency grant MNaims (ANR-17-CE17-0012-01). The Dutch studies were supported by grants from the Dutch Kidney Foundation to JMH and JFW (Nierstichting Nederland grant OW08 and grant KJPB11.021). We would like to thank the Population Architecture Using Genomics and Epidemiology (PAGE) consortium, funded by the National Human Genome Research Institute (NHGRI) with co-funding from the NIMHD, for providing population controls for this study. For full acknowledgment of the PAGE consortium, please see Supplementary Materials. The funding sources were not involved in the study design, collection, analysis, and interpretation of data, writing of the report, or in the decision to submit the paper for publication.
Published: 2020

30. 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

31. Milestones in nephrology and welcoming the future: the 61st anniversary of the International Society of Nephrology

Author: Pierre Ronco, Brad Rovin, Masaomi Nangaku, Christina Wyatt, Vivek Jha, P. Toby Coates, Olivier Devuyst, Tilman B. Drueke, Jürgen Floege, Agnes B. Fogo, T. Alp Ikizler, Jai Radhakrishnan, and Germaine Wong
Subjects: Nephrology, medicine.medical_specialty, Anniversaries and Special Events, business.industry, Family medicine, Internal medicine, medicine, Humans, Glomerulonephritis, IGA, business
Published: 2020

32. Management of acute kidney injury in symptomatic multiple myeloma

Author: Jean Paul Fermand, Frank Bridoux, Mohamed Belmouaz, Samih H. Nasr, Virginie Royal, Nelson Leung, and Pierre Ronco
Subjects: 0301 basic medicine, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, Urology, Nephropathy, Bortezomib, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, medicine, Humans, Dialysis, Multiple myeloma, Kidney, business.industry, Acute kidney injury, Acute Kidney Injury, medicine.disease, Transplantation, 030104 developmental biology, medicine.anatomical_structure, Nephrology, Quality of Life, Immunoglobulin Light Chains, Hemodialysis, business, Multiple Myeloma, medicine.drug
Abstract: Symptomatic multiple myeloma is commonly complicated by acute kidney injury through various mechanisms. The most frequent is the precipitation of monoclonal free light chains with uromodulin in the distal tubules, defining light chain cast nephropathy. Early diagnosis and identification of the cause of acute kidney injury are required for optimizing management and avoiding chronic kidney injury that strongly affects quality of life and patient survival. In light chain cast nephropathy, often manifesting with severe acute kidney injury, renal recovery requires urgent intervention based on vigorous rehydration, correction of precipitating factors, and efficient anti–plasma cell chemotherapy to rapidly reduce the secretion of nephrotoxic free light chains. Currently, the association of the proteasome inhibitor bortezomib with high-dose dexamethasone is the standard regimen in newly diagnosed patients. The addition of another drug such as cyclophosphamide or an immunodulatory agent may improve free light chain response but raises tolerance concerns in frail patients. Further studies are warranted to confirm the role of anti-CD38 monoclonal antibodies, whose efficacy and tolerance have been documented in patients without renal impairment. Despite controversial results from randomized studies, recent data suggest that in patients with light chain cast nephropathy and acute kidney injury requiring dialysis, the combination of chemotherapy with free light chain removal through high-cutoff hemodialysis may increase renal response recovery rates. Kidney biopsy may be helpful in guiding management and assessing renal prognosis that appears to depend on the extent of cast formation and interstitial fibrosis/tubular atrophy. Because of continuous improvement in life expectancy of patients with multiple myeloma, renal transplantation is likely to be increasingly considered in selected candidates.
Published: 2020

33. Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome

Author: Xiaoyuan Jia, Tomohiko Yamamura, Rasheed Gbadegesin, Michelle T. McNulty, Kyuyong Song, China Nagano, Yuki Hitomi, Dongwon Lee, Yoshihiro Aiba, Seik-Soon Khor, Kazuko Ueno, Yosuke Kawai, Masao Nagasaki, Eisei Noiri, Tomoko Horinouchi, Hiroshi Kaito, Riku Hamada, Takayuki Okamoto, Koichi Kamei, Yoshitsugu Kaku, Rika Fujimaru, Ryojiro Tanaka, Yuko Shima, Jiwon Baek, Hee Gyung Kang, Il-Soo Ha, Kyoung Hee Han, Eun Mi Yang, Asiri Abeyagunawardena, Brandon Lane, Megan Chryst-Stangl, Christopher Esezobor, Adaobi Solarin, Claire Dossier, Georges Deschênes, Marina Vivarelli, Hanna Debiec, Kenji Ishikura, Masafumi Matsuo, Kandai Nozu, Pierre Ronco, Hae Il Cheong, Matthew G. Sampson, Katsushi Tokunaga, Kazumoto Iijima, Yoshinori Araki, Yoshinobu Nagaoka, Yasuyuki Sato, Asako Hayashi, Toshiyuki Takahashi, Hayato Aoyagi, Michihiko Ueno, Masanori Nakanishi, Nariaki Toita, Kimiaki Uetake, Norio Kobayashi, Shoji Fujita, Kazushi Tsuruga, Naonori Kumagai, Hiroki Kudo, Eriko Tanaka, Tae Omori, Mari Okada, Yoshiho Hatai, Tomohiro Udagawa, Yaeko Motoyoshi, Masao Ogura, Mai Sato, Yuji Kano, Motoshi Hattori, Kenichiro Miura, Yutaka Harita, Shoichiro Kanda, Emi Sawanobori, Anna Kobayashi, Manabu Kojika, Yoko Ohwada, Kunimasa Yan, Hiroshi Hataya, Chikako Terano, Ryoko Harada, Yuko Hamasaki, Junya Hashimoto, Shuichi Ito, Hiroyuki Machida, Aya Inaba, Takeshi Matsuyama, Miwa Goto, Masaki Shimizu, Kazuhide Ohta, Yohei Ikezumi, Takeshi Yamada, Toshiaki Suzuki, Soichi Tamamura, Yukiko Mori, Yoshihiko Hidaka, Daisuke Matsuoka, Tatsuya Kinoshita, Shunsuke Noda, Masashi Kitahara, Naoya Fujita, Satoshi Hibino, Shogo Minamikawa, Keita Nakanishi, Junya Fujimura, Nana Sakakibara, Yuya Aoto, Shinya Ishiko, Kyoko Kanda, Yosuke Inaguma, Yuya Hashimura, Shingo Ishimori, Naohiro Kamiyoshi, Takayuki Shibano, Yasuhiro Takeshima, Hiroaki Ueda, Akira Ashida, Hideki Matsumura, Takuo Kubota, Taichi Kitaoka, Yusuke Okuda, Toshihiro Sawai, Tomoyuki Sakai, Taketsugu Hama, Mikiya Fujieda, Masayuki Ishihara, Shigeru Itoh, Takuma Iwaki, Maki Shimizu, Koji Nagatani, Shoji Kagami, Maki Urushihara, Manao Nishimura, Miwa Yoshino, Ken Hatae, Maiko Hinokiyama, Rie Kuroki, Yasufumi Ohtsuka, Masafumi Oka, Shinji Nishimura, Tadashi Sato, Seiji Tanaka, Ayuko Zaitsu, Hitoshi Nakazato, Hiroshi Tamura, Koichi Nakanishi, Min Hyun Cho, Tae-Sun Ha, Ji Hyun Kim, Peong Gang Park, Myung Hyun Cho, Alejandro Quiroga, Asha Moudgil, Blanche Chavers, Charles Kwon, Corinna Bowers, Deb Gipson, Deepa Chand, Donald Jack Weaver, Elizabeth Abraham, Halima Janjua, Jen-Jar Lin, Larry Greenbaum, Mahmoud Kallash, Michelle Rheault, Nilka De Jeus Gonzalez, Patrick Brophy, Shashi Nagaraj, Susan Massengill, Tarak Srivastava, Tray Hunley, Yi Cai, Abiodun Omoloja, Cynthia Silva, Adebowale Adeyemo, Shenal Thalgahagoda, Jameela A. Kari, Sherif El Desoky, Mohammed Abdelhadi, Rachida Akil, Sonia Azib, Romain Basmaci, Gregoire Benoist, Philippe Bensaid, Philippe Blanc, Olivia Boyer, Julie Bucher, Anne Chace, Arnaud Chalvon, Marion Cheminee, Sandrine Chendjou, Patrick Daoud, Ossam Elias, Chantal Gagliadone, Vincent Gajdos, Aurélien Galerne, Evelyne Jacqz Aigrain, Lydie Joly Sanchez, Mohamed Khaled, Fatima Khelfaoui, Yacine Laoudi, Anis Larakeb, Tarek Limani, Fouad Mahdi, Alexis Mandelcwaijg, Stephanie Muller, Kacem Nacer, Sylvie Nathanson, Béatrice Pellegrino, Isabelle Pharaon, Véronica Roudault, Sébastien Rouget, Marc Saf, Tabassom Simon, Cedric Tahiri, Tim Ulinski, Férielle Zenkhri, CHU Tenon [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Tumor Necrosis Factor Ligand Superfamily Member 15, 0301 basic medicine, podocyte, Steroid-sensitive nephrotic syndrome, 030232 urology & nephrology, Polygenic disease, glomerulus, Biology, Monogenic disease, Article, 03 medical and health sciences, 0302 clinical medicine, pediatric nephrology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Child, Gene, Allele frequency, Congenital nephrotic syndrome, Alleles, ComputingMilieux_MISCELLANEOUS, Genetics, nephrotic syndrome, Membrane Proteins, Odds ratio, medicine.disease, 3. Good health, 030104 developmental biology, Haplotypes, Nephrology, Mutation, Steroids, Nephrotic syndrome, Genome-Wide Association Study
Abstract: To understand the genetics of steroid-sensitive nephrotic syndrome (SSNS), we conducted a genome-wide association study in 987 childhood SSNS patients and 3,206 healthy controls with Japanese ancestry. Beyond known associations in the HLA-DR/DQ region, common variants in NPHS1-KIRREL2 (rs56117924, P=4.94E-20, odds ratio (OR) =1.90) and TNFSF15 (rs6478109, P=2.54E-8, OR=0.72) regions achieved genome-wide significance and were replicated in Korean, South Asian and African populations. Trans-ethnic meta-analyses including Japanese, Korean, South Asian, African, European, Hispanic and Maghrebian populations confirmed the significant associations of variants in NPHS1-KIRREL2 (P(meta)=6.71E-28, OR=1.88) and TNFSF15 (P(meta)=5.40E-11, OR=1.33) loci. Analysis of the NPHS1 risk alleles with glomerular NPHS1 mRNA expression from the same person revealed allele specific expression with significantly lower expression of the transcript derived from the risk haplotype (Wilcox test p=9.3E-4). Because rare pathogenic variants in NPHS1 cause congenital nephrotic syndrome of the Finnish type (CNSF), the present study provides further evidence that variation along the allele frequency spectrum in the same gene can cause or contribute to both a rare monogenic disease (CNSF) and a more complex, polygenic disease (SSNS).
Published: 2020

34. Kidney International and the COVID-19 infection

Author: Tilman B. Drüeke, T. Alp Ikizler, Brad H. Rovin, Jürgen Floege, Jai Radhakrishnan, Germaine Wong, Pierre Ronco, Christina M. Wyatt, Masaomi Nangaku, P. Toby Coates, Agnes B. Fogo, Olivier Devuyst, University of Zurich, Rovin, Brad H, Ohio State University [Columbus] (OSU), 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 Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Associate Editors, Entire Editorial Team, Bodescot, Myriam, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UCL - SSS/IREC/NEFR - Pôle de Néphrologie, and UCL - (SLuc) Service de néphrologie
Subjects: Nephrology, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), short review process, 610 Medicine & health, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, 10052 Institute of Physiology, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Kidney, 2727 Nephrology, business.industry, COVID-19, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Virology, medicine.anatomical_structure, 030228 respiratory system, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 570 Life sciences, biology, business
Abstract: International audience
Published: 2020

35. Screening for Cancer in Patients with Glomerular Diseases

Author: Emmanuelle Plaisier, Pierre Ronco, 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), 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 (SU), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [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), and Gestionnaire, Hal Sorbonne Université
Subjects: Nephrology, Oncology, Epidemiology, Paraneoplastic Syndromes, membranoproliferative glomerulonephritis, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, neoplasms, human PLA2R1 protein, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Glomerulonephritis, Membranous, nephrologists, 0302 clinical medicine, cytosolic phospholipases A2, phospholipase A2 receptors, Membranoproliferative glomerulonephritis, risk factors, humans, ComputingMilieux_MISCELLANEOUS, Cancer, Kidney, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, nephrotic syndrome, phospholipases A2, follow-up studies, 3. Good health, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Perspectives, medicine.medical_specialty, kidney, thrombospondins, recurrence, nephrology, Malignancy, immunosuppressive agents, 03 medical and health sciences, Membranous nephropathy, Internal medicine, medicine, In patient, Autoantibodies, treatment failure, Transplantation, urogenital system, business.industry, Receptors, Phospholipase A2, cost-benefit analysis, membranous nephropathy, medicine.disease, early detection of cancer, business, Nephrotic syndrome, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: The diagnosis of malignancy in the setting of nephrotic syndrome is associated with a poor overall and kidney survival regardless of whether the glomerular disease represents a paraneoplastic manifestation or the cancer is a coincidental finding. The diagnosis of the neoplasia leads to consideration
Published: 2020

36. Molecular Pathogenesis of Membranous Nephropathy

Author: Hanna Debiec, Pierre Ronco, CHU Tenon [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], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, 0301 basic medicine, 030232 urology & nephrology, Human leukocyte antigen, Glomerulonephritis, Membranous, Epitope, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, Antigen, Membranous nephropathy, HLA Antigens, Risk Factors, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, Genetic Predisposition to Disease, ComputingMilieux_MISCELLANEOUS, Autoantibodies, Autoimmune disease, Thrombospondin, biology, business.industry, Receptors, Phospholipase A2, Infant, Newborn, medicine.disease, 3. Good health, Complement system, 030104 developmental biology, Immunology, Disease Progression, biology.protein, Neprilysin, Antibody, Thrombospondins, business, Biomarkers
Abstract: Membranous nephropathy is a noninflammatory autoimmune disease of the kidney glomerulus, characterized by the formation of immune deposits, complement-mediated proteinuria, and risk of renal failure. Considerable advances in understanding the molecular pathogenesis have occurred with the identification of several antigens [neutral endopeptidase, phospholipase A2 receptor (PLA2R), thrombospondin domain-containing 7A (THSD7A)] in cases arising from the neonatal period to adulthood and the characterization of antibody-binding domains (that is, epitopes). Immunization against PLA2R occurs in 70% to 80% of adult cases. The development of highly specific and sensitive assays of circulating antibodies has induced a paradigm shift in diagnosis and treatment monitoring. In addition, several interacting loci in HLA-DQ, HLA-DR, and PLA2R1, as well as classical human leukocyte antigen (HLA)-D alleles have been identified as being risk factors, depending on a patient's ethnicity. Additionally, mechanisms of antibody pathogenicity and pathways of complement activation are now better understood. Further research is mandatory for designing new therapeutic strategies, including the identifying triggering events, the molecular bases of remission and progression, and the T cell epitopes involved.
Published: 2020

37. KDIGO Controversies Conference on onco-nephrology: kidney disease in hematological malignancies and the burden of cancer after kidney transplantation

Author: Farhad R. Danesh, Kunitoshi Iseki, Mitchell H. Rosner, Laura Cosmai, Kenar D. Jhaveri, Michael Cheung, Hatem Amer, Manuel Macía, Germaine Wong, Artur Jurczyszyn, Alicja Dębska-Ślizień, Rumeyza Kazancioglu, Elena Zakharova, Romano Danesi, Jeremy R. Chapman, Pierre Ronco, Aristotelis Bamias, Yang Li, Amit Lahoti, Anitha Vijayan, Petra Tesarova, Maria Jose Soler Romeo, Abhijat Kitchlu, Verônica Torres da Costa e Silva, Morie A. Gertz, Eisei Noiri, Walter M. Stadler, Wolfgang C. Winkelmayer, Maurizio Gallieni, Camillo Porta, Filippo De Stefano, Dionysios Mitropoulos, Christian Kollmannsberger, Paul E. Stevens, Edgar A. Jaimes, Vladimír Tesař, Gernot Beutel, Xiaohong Chen, Ali K. Abu-Alfa, Ben Sprangers, Biruh Workeneh, David H. Vesole, Jolanta Malyszko, Jan T. Kielstein, Ondřej Viklický, David C. Wheeler, Jerzy Chudek, Mark A. Perazella, Motoko Yanagita, and Takeshi Matsubara
Subjects: 0301 basic medicine, Nephrology, medicine.medical_specialty, medicine.medical_treatment, 030232 urology & nephrology, kidney transplantation, chemotherapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Intensive care medicine, Kidney transplantation, Multiple myeloma, Dialysis, business.industry, Acute kidney injury, Cancer, medicine.disease, Tumor lysis syndrome, 030104 developmental biology, chronic kidney disease, oncology, tumor lysis syndrome, business, Kidney disease
Abstract: The bidirectional relationship between cancer and chronic kidney disease (CKD) is complex. Patients with cancer, particularly those with hematological malignancies such as multiple myeloma and lymphoma, are at increased risk of developing acute kidney injury and CKD. On the other hand, emerging evidence from large observational registry analyses have consistently shown that cancer risk is increased by at least 2- to 3-fold in kidney transplant recipients, and the observed increased risk occurs not only in those who have received kidney transplants but also in those on dialysis and with mild- to moderate-stage CKD. The interactions between cancer and CKD have raised major therapeutic and clinical challenges in the management of these patients. Given the magnitude of the problem and uncertainties, and current controversies within the existing evidence, Kidney Disease: Improving Global Outcomes (KDIGO) assembled a global panel of multidisciplinary clinical and scientific expertise for a controversies conference on onco-nephrology to identify key management issues in nephrology relevant to patients with malignancy. This report covers the discussed controversies in kidney disease in hematological malignancies, as well as cancer after kidney transplantation. An overview of future research priorities is also discussed.
Published: 2020

38. Early experience with COVID-19 in kidney transplantation

Author: Jürgen Floege, Tilman B. Drüeke, T. Alp Ikizler, Agnes B. Fogo, Masaomi Nangaku, Pierre Ronco, P. Toby Coates, Jai Radhakrishnan, Olivier Devuyst, Germaine Wong, Brad H. Rovin, Christina M. Wyatt, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, University of Zurich, and Coates, P Toby
Subjects: Nephrology, medicine.medical_specialty, 2727 Nephrology, biology, Coronavirus disease 2019 (COVID-19), business.industry, 610 Medicine & health, biology.organism_classification, medicine.disease, medicine.disease_cause, Virology, 10052 Institute of Physiology, Transplantation, Pneumonia, Internal medicine, Pandemic, 570 Life sciences, Medicine, business, Betacoronavirus, Kidney transplantation, Coronavirus
Abstract: In this edition of Kidney International, we publish 2 series of patients who had undergone kidney transplantation during the coronavirus disease 2019 (COVID-19) pandemic that have taken different approaches to transplant immunosuppressive therapy and antiviral treatment in the early days of the developing pandemic in the United Kingdom and Italy. The first series of 7 cases of COVID-19 infection in patients who had undergone kidney transplantation comes from St. George's, St. Helier’s, and King’s College Hospitals in south London, United Kingdom,1 and the second series of 20 cases originates from Spedali Civili University Hospital in Brescia, Italy. [...]
Published: 2020

39. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy

Author: Gema Fernández-Juárez, Jorge Rojas-Rivera, Anne-Els van de Logt, Joana Justino, Angel Sevillano, Fernando Caravaca-Fontán, Ana Ávila, Cristina Rabasco, Virginia Cabello, Alfonso Varela, Montserrat Díez, Guillermo Martín-Reyes, Marian Goicoechea Diezhandino, Luis F. Quintana, Irene Agraz, Juan Ramón Gómez-Martino, Mercedes Cao, Antolina Rodríguez-Moreno, Begoña Rivas, Cristina Galeano, Jose Bonet, Ana Romera, Amir Shabaka, Emmanuelle Plaisier, Mario Espinosa, Jesus Egido, Alfonso Segarra, Gérard Lambeau, Pierre Ronco, Jack Wetzels, Manuel Praga, Fernando Caravaca-Fontan, Hernando Trujillo, Eduardo Gutiérrez, Gema Fernandez Juarez, Alberto Ortiz, Marian Goicoechea, Úrsula Verdalles, Alfons Segarra, Lara Perea, Ildefonso Valera, Mónica Martín, Miguel Angel Pérez Valdivia, Miquel Blasco, Andrés López Muñiz, Ana Avila, Tamara Malek, Montserrat Diaz, Iara DaSilva, Jordi Bonet, Maruja Navarro, Ana Huerta, Ezequiel Rodríguez-Paternina, Ana Vigil, Roberto Alcázar, Vicente Paraíso, Vicente Barrio, Julia Hofstra, Institut Català de la Salut, [Fernández-Juárez G] Nephrology Division, Hospital Universitario Fundación Alcorcón, Madrid, Spain. [Rojas-Rivera J] Nephrology Division, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. [Logt AV] Nephrology Division, Radboud University Medical Center, Nijmegen, The Netherlands. [Justino J] Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), Université Côte d’Azur, Centre National de la Recherche Scientifique (CNRS), Valbonne Sophia Antipolis, France. [Sevillano A, Caravaca-Fontán F] Nephrology Division, Instituto de Investigación Hospital Universitario 12 Octubre, Madrid, Spain. [Agraz I] Divisió de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Nephrology Division, Hospital Universitario Fundación Alcorcón, Madrid, Spain, Nephrology Division, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain, Radboud Institute for Health Sciences, Radboud University Medical Center [Nijmegen], Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 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), Hospital Universitario 12 de Octubre [Madrid], Dr Peset University Hospital, Hospital Reina Sofia, Cordoba, Hospital Universitario Virgen del Rocío [Sevilla], Hospital of Virgen de la Victoria de Malaga, Institut Investigacions Biomèdiques (IBB) Sant Pau [Barcelona, Spain], Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], Hospital General Universitario 'Gregorio Marañón' [Madrid], Department of Nephrology, Hospital Clinic, Barcelona, Spain., Vall d'Hebron University Hospital [Barcelona], San Pedro de Alcantara Hospital [Cáceres, Espagne], Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Universidade da Coruña (UDC), Spain, Hospital Clinico San Carlos, Hospital Clínico San Carlos, Hospital Universitario La Paz [Madrid, Espagne], Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Germans Trias i Pujol Hospital, Universitat Autònoma de Barcelona (UAB), Hospital General Universitario de Ciudad Real [Ciudad Real, Spain], 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), Radboud Institute for Health Sciences [Nijmegen, the Netherlands], Hospital Universitario Fundación Alcorcón, Hospital Universitario Fundación Jiménez Díaz [Madrid, Spain], Barcelona Centre for International Health Research, Hospital Clinic (CRESIB), Universitat de Barcelona (UB), Hospital Universitario, A Coruña, Fundació Puigvert [Barcelona, Spain], Germans Trias i Pujol University Hospital [Badalona, Barcelona, Spain] (GTPUH), Hospital Universitario Puerta de Hierro-Majadahonda [Madrid, Spain], Getafe University Hospital, Madrid, Severo Ochoa Hospital, Hospital Universitario Infanta Leonor [Madrid], Del Henares Hospital, Hospital Universitario Infanta Sofía, Radboud University Medical Center, PO Box 9101, 6500 HB Nijmegen, The Netherlan ds, Lambeau, Gerard, Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Hospital Regional Universitario de Málaga [Spain], Barcelona Autonomous University, Common and Rare Kidney Diseases = Maladies Rénales Fréquentes et Rares: des Mécanismes Moléculaires à la Médecine Personnalisée (CORAKID), and Germans Trias i Pujol University Hospital
Subjects: 0301 basic medicine, medicine.medical_specialty, Cyclophosphamide, medicine.drug_class, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores], Other subheadings::Other subheadings::/drug therapy [Other subheadings], Gastroenterology, Tacrolimus, Primary membranous nephropathy, law.invention, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Randomized controlled trial, law, Internal medicine, medicine, Corticosteroids, ComputingMilieux_MISCELLANEOUS, business.industry, Male Urogenital Diseases::Urologic Diseases::Kidney Diseases [DISEASES], diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], medicine.disease, Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], 3. Good health, [SDV] Life Sciences [q-bio], Regimen, 030104 developmental biology, Nephrology, Avaluació de resultats (Assistència sanitària), Corticosteroid, Rituximab, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business, Nephrotic syndrome, enfermedades urogenitales masculinas::enfermedades urológicas::enfermedades renales [ENFERMEDADES], Ronyons - Malalties - Tractament, medicine.drug
Abstract: Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Red de Investigación Renal (RedInRen); European Renal Association-European Dialysis and Transplant Association (ERA-EDTA); Fundación Renal Iñigo Álvarez de Toledo (FRIAT); Fundación para la Investigación Biomédica Hospital 12 de Octubre (i+12); Centre National de la Recherche Scientifique; Fondation Maladies Rares (LAM-RD_20170304); National Research Agency (ANR, grants MNaims ANR-17-CE17-0012-01); "Investments for the Future" Laboratory of Excellence SIGNALIFE, a network for innovation on signal transduction pathways in life sciences (ANR-11-LABX-0028-01); Initiative of Excellence (IDEX; UCAJedi ANR-15-IDEX-01); Fondation pour la Recherche Médicale (FRM, ING20140129210, DEQ20180339193, FDT201805005509). A cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). The primary outcome was complete or partial remission of nephrotic syndrome at 24 months. This composite outcome occurred in 36 patients (83.7%) in the corticosteroid-cyclophosphamide group and in 25 patients (58.1%) in the tacrolimus-rituximab group (relative risk 1.44; 95% confidence interval 1.08 to 1.92). Complete remission at 24 months occurred in 26 patients (60%) in the corticosteroid-cyclophosphamide group and in 11 patients (26%) in the tacrolimus-rituximab group (2.36; 1.34 to 4.16). Anti-PLA2R titers showed a significant decrease in both groups but the proportion of anti-PLA2R-positive patients who achieved immunological response (depletion of anti-PLA2R antibodies) was significantly higher at three and six months in the corticosteroid-cyclophosphamide group (77% and 92%, respectively), as compared to the tacrolimus-rituximab group (45% and 70%, respectively). Relapses occurred in one patient in the corticosteroid-cyclophosphamide group, and three patients in the tacrolimus-rituximab group. Serious adverse events were similar in both groups. Thus, treatment with corticosteroid-cyclophosphamide induced remission in a significantly greater number of patients with primary membranous nephropathy than tacrolimus-rituximab.
Published: 2020

40. How to assess kidney function in oncology patients

Author: Jolanta Malyszko, Giovambattista Capasso, Anna Capasso, Paweł Kulicki, Davide Viggiano, Pierre Ronco, Petra Tesarova, Paul E. Stevens, Michael W. Lee, Joanna Matuszkiewicz-Rowińska, Malyszko, J., Lee, M. W., Capasso, G., Kulicki, P., Matuszkiewicz-Rowinska, J., Ronco, P., Stevens, P., Tesarova, P., Viggiano, D., and Capasso, A.
Subjects: 0301 basic medicine, medicine.medical_specialty, Urinalysis, biomarkers, glomerular filtration rate, kidney function, oncology, medicine.medical_treatment, Population, 030232 urology & nephrology, Renal function, Kidney, Kidney Function Tests, Nephrotoxicity, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, medicine, Humans, Intensive care medicine, education, education.field_of_study, Chemotherapy, medicine.diagnostic_test, business.industry, urogenital system, Clinical trial, 030104 developmental biology, Nephrology, Creatinine, Toxicity, biomarker, Oncology patients, business
Abstract: Assessment of kidney function in oncology patients is a fundamental factor in profiling the survival risk, determining the appropriate dose of chemotherapeutic drugs, and defining a patient eligibility for clinical trials with novel agents. Both overestimation and underestimation of kidney function may affect the treatment efficacy and outcomes. Overestimation may lead to overdosing or inappropriate agent selection and the corresponding toxicity, whereas underestimation may be responsible for underdosing or inappropriate agent exclusion and subsequent treatment failure. This is of utmost importance in patients with cancer. Evaluation of kidney function is not only limited to the estimation of glomerular filtration rate or creatinine clearance. An accurate assessment of kidney function is advisable to reduce variability in decision making and ultimately the therapeutic outcomes of toxicity and clinical benefit. Therefore, additional studies are needed to investigate the validity of currently used formulas estimating kidney function in this population as well as their applicability to traditional chemotherapy, novel targeted therapies, and immunotherapies. Because of rapid discovery and development of new cancer agents, a reliable and comprehensive manner to screen for potential nephrotoxicity is critically important. As kidney function not only is limited to glomerular filtration rate changes but also involves tubular and even vascular dysfunction, urinalysis and kidney imaging studies should also be considered before therapeutic decisions are taken. However, several questions remain regarding these new technologies such as kidney-on-a-chip systems for the assessment of kidney function and injury, particularly in oncology, and it has yet to be implemented in clinical practice.
Published: 2020

41. Podocyte Antigen Staining to Identify Distinct Phenotypes and Outcomes in Membranous Nephropathy: A Retrospective Multicenter Cohort Study

Author: Hanna Debiec, Ashley Broughton, Michel Wauthier, Albert Hermant, Benoit Georges, Abdelhamid Lalaoui, Diego Castanares-Zapatero, Matthieu Lemaire, Fabienne Mestrez, Yves Pirson, Nicolas Hanset, Nada Kanaan, Gregory Van Ingelgem, Roxana Sava, Benoit Guillaume, Jean-Michel Pochet, Frédéric Debelle, Lionel Mazzoleni, Valentine Gillion, Michel Tintillier, Nicolas Cecere, Philippe Leroy, Jean-Claude Stolear, Gabriela Migali, Benjamin Seront, Pierre Ronco, Corinne Langen, Michele Muller, Georges Cornet, Arnaud Devresse, Guy Fomegne, Nathalie Demoulin, Yvan Philips, Charlotte Van Ende, Assma Ballout, Delphine Halleux, Nadejda Ranguelov, Pierre-Yves Decleire, Ahmed Goubella, Christine Hurtgen, Ralph Crott, Pauline Biller, Johann Morelle, An Van Audenhove, Philippe Durieux, Caroline Clerckx, Nathalie Godefroid, Dominique Becker, Charles Cuvelier, Selda Aydin, Hélène Munyentwali, Francois Reginster, Jean-Louis Christophe, Jean-Philippe Lengelé, René Cuvelier, Benoit Buysschaert, Joëlle Ghysen, Jean-Jacques Lafontaine, Jean-François Cambier, Eric Goffin, Fabrice Gankam, Agnès Dejardin, Olivier Mat, Laura Labriola, Jean Jamez, Jean-Pierre Cosyns, Gaetan Clerbaux, Pierre Bernis, Michel Jadoul, Miguel-Ange Guillen-Anaya, Gaëlle Gillerot, Marie Rommelaere, Bénédicte Vanderperren, Joseph Mbaba Mena, Alina Tirdea, Liesbeth Smets, Frédéric Houssiau, Zuzana Rihova, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - SSS/IREC/MORF - Pôle de Morphologie, UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales, UCL - (SLuc) Service de néphrologie, UCL - (SLuc) Service d'anatomie pathologique, UCL - (SLuc) Service de soins intensifs, UCL - (SLuc) Service de rhumatologie, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Cliniques Universitaires Saint-Luc [Bruxelles], Lille économie management - UMR 9221 (LEM), Université d'Artois (UA)-Université catholique de Lille (UCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Des Maladies Rénales Rares aux Maladies Fréquentes, Remodelage et Réparation, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Expérimentale et Clinique (IREC), ANR-17-CE17-0012,MNaims,Dissection moléculaire de la glomérulonéphrite extramembraneuse liée à PLA2R1: vers l'identification de nouveaux biomarqueurs cliniques(2017), and UCL - SSS/IREC - Institut de recherche expérimentale et clinique
Subjects: Male, Biopsy, 030232 urology & nephrology, glomerular disease, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, Glomerulonephritis, Membranous, phospholipase A(2) receptor (PLA(2)R), 0302 clinical medicine, Medicine, thrombospondin type 1 domain-containing 7A (THSD7A), 030212 general & internal medicine, Kidney, immunostaining, medicine.diagnostic_test, Podocytes, nephrotic syndrome, Middle Aged, 3. Good health, medicine.anatomical_structure, Phenotype, Nephrology, Disease Progression, outcome, Female, Adult, medicine.medical_specialty, kidney biopsy, thrombospondin type 1 domain-containing 7A, 03 medical and health sciences, Membranous nephropathy, Internal medicine, Humans, cancer, Aged, Autoantibodies, Retrospective Studies, phospholipase A2 receptor, Lupus erythematosus, Staining and Labeling, business.industry, membranous nephropathy, Cancer, Retrospective cohort study, medicine.disease, podocyte antigen, business, Nephrotic syndrome, Kidney disease, Follow-Up Studies, Membranous nephropathy (MN), malignancy
Abstract: Rationale & Objective Membranous nephropathy (MN) is characterized by the deposition of immune complexes along glomerular basement membranes. M-Type phospholipase A2 receptor (PLA2R), thrombospondin type 1 domain-containing 7A (THSD7A), exostosin 1 and 2 (EXT1/2), and neural epidermal growth factor-like 1 protein (NELL-1) have been identified as established or potential podocyte antigens in MN. We investigated the association of podocyte antigen staining with MN clinical phenotype and outcomes. Study Design Multicenter retrospective cohort study. Setting & Participants 177 consecutive patients with MN unrelated to lupus erythematosus, identified after screening of 3,875 native kidney biopsies performed in the Belgian UCLouvain Kidney Disease Network from 2000 through 2018. Predictor Positive immunostaining for podocyte antigens on archived kidney biopsy samples. Outcomes Association with different phenotypes (baseline characteristics of patients and pathologic findings on kidney biopsy), time to cancer and to kidney failure. Analytical Approach Kaplan-Meier estimates and Cox regression analyses to assess time to cancer and kidney failure. Results 177 patients were followed up for a median of 4.0 (IQR, 1.3-8.0) years. Diagnosis of PLA2R-positive (PLA2R+), THSD7A+, and double-negative (PLA2R−/THSD7A−) MN was made in 117 (66.1%), 6 (3.4%), and 54 (30.5%) patients, respectively. Progression to kidney failure was similar in all groups. Although the number of patients with THSD7A+ MN was small, they showed a higher incidence (50%) and increased risk for developing cancer during follow-up (adjusted HR, 5.0 [95% CI, 1.4-17.9]; P = 0.01). 8% and 5% of patients with double-negative MN stained positively for EXT1/2 and NELL-1, respectively. Most patients with EXT1/2+ MN were women, had features of systemic autoimmunity, and showed glomerular C1q deposits. Limitations Retrospective design; small number of patients in the THSD7A group; lack of evaluation of immunoglobulin G subclasses deposition. Conclusions Our real-world data describe the relative prevalence of subgroups of MN and support the hypothesis that a novel classification of MN based on podocyte antigen staining may be clinically relevant.
Published: 2020

42. Standardized reporting of monoclonal immunoglobulin-associated renal diseases: recommendations from a Mayo Clinic/Renal Pathology Society Working Group

Author: Shaji Kumar, Fernando G. Cosio, David L. Murray, Mariam P. Alexander, Gerald B. Appel, Mark Haas, Dario Roccatello, Ladan Zand, Virginie Royal, Hatem Amer, Loren P. Herrera Hernandez, Cynthia C. Nast, Richard J. Glassock, Anthony Chang, Antonello Pani, An S. De Vriese, Pingchuan Zhang, Kelly D. Smith, Nelson Leung, Vivette D. D'Agati, Ashutosh D. Wechalekar, Sanjeev Sethi, Glen S. Markowitz, Michael B. Stokes, Aishwarya Ravindran, Samih H. Nasr, Maria M. Picken, Pierre Ronco, Fernando C. Fervenza, Jack F.M. Wetzels, Mayo Clinic [Rochester], David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), New York University Langone Medical Center (NYU Langone Medical Center), NYU System (NYU), Melting the frontiers between Light, Shape and Matter (MANAO), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS)-Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Laboratoire Photonique, Numérique et Nanosciences (LP2N), and Université de Bordeaux (UB)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS)-Institut d'Optique Graduate School (IOGS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: medicine.medical_specialty, Kidney, business.industry, Paraproteinemias, Monoclonal immunoglobulin, monoclonal gammopathy of renal significance, kidney biopsy glomerulonephritis, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, monoclonal Ig, medicine.anatomical_structure, Renal pathology, Nephrology, Internal medicine, medicine, Humans, Kidney Diseases, Paraproteins, Renal disorders Radboud Institute for Health Sciences [Radboudumc 11], business
Abstract: Contains fulltext : 225148.pdf (Publisher’s version ) (Closed access)
Published: 2020

43. Rituximab in Patients With Phospholipase A2 Receptor-Associated Membranous Nephropathy and Severe CKD

Author: Nicolas Hanset, Karine Dahan, Patrick Fievet, Pierre Ronco, Catherine Johanet, P.A. Michel, Emmanuelle Plaisier, Laurent Mesnard, Johann Morelle, Emmanuel Esteve, Jean-Jacques Boffa, UCL - SSS/IREC/NEFR - Pôle de Néphrologie, UCL - (SLuc) Service de néphrologie, UCL - (SLuc) Service de médecine interne générale, Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Cliniques Universitaires Saint-Luc [Bruxelles], 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 Tenon [APHP], Service d'immunologie et hématologies biologiques [Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Sorbonne Université (SU)-CHU Saint-Antoine [APHP], 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), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immunologie et hématologies biologiques [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], 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: medicine.medical_specialty, Urinary system, PLA2R, 030232 urology & nephrology, Renal function, 030204 cardiovascular system & hematology, lcsh:RC870-923, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, rituximab, Membranous nephropathy, Clinical Research, Interquartile range, Internal medicine, medicine, CKD, ESKD, business.industry, membranous nephropathy, immunosuppressive treatment, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, 3. Good health, Regimen, Nephrology, Rituximab, business, Nephrotic syndrome, medicine.drug, Kidney disease
Abstract: Introduction Patients with phospholipase A2 receptor (PLA2R)–associated membranous nephropathy and stage 4 or 5 chronic kidney disease are at high risk of end-stage kidney disease. In recent years, rituximab (RTX) emerged as a safe and efficient treatment for patients with PLA2R-associated membranous nephropathy. Whether its use is also appropriate in patients with an estimated glomerular filtration rate, Graphical abstract
Published: 2020

44. KDIGO Controversies Conference on onco-nephrology: understanding kidney impairment and solid-organ malignancies, and managing kidney cancer

Author: Romano Danesi, Anitha Vijayan, Verônica Torres da Costa e Silva, Jolanta Malyszko, Maria Jose Soler Romeo, Maurizio Gallieni, Edgar A. Jaimes, David H. Vesole, Takeshi Matsubara, Christian Kollmannsberger, Camillo Porta, Motoko Yanagita, Walter M. Stadler, Dionysios Mitropoulos, Morie A. Gertz, Gernot Beutel, Ben Sprangers, Biruh Workeneh, Elena Zakharova, Aristotelis Bamias, Jerzy Chudek, Xiaohong Chen, Kenar D. Jhaveri, Kunitoshi Iseki, Amit Lahoti, Ali K. Abu-Alfa, Paul E. Stevens, Laura Cosmai, Michael Cheung, Mark A. Perazella, Eisei Noiri, Filippo De Stefano, Wolfgang C. Winkelmayer, Jan T. Kielstein, Abhijat Kitchlu, Manuel Macía, Mitchell H. Rosner, Farhad R. Danesh, Rumeyza Kazancioglu, David C. Wheeler, ladimír Tesař, Ondřej Viklický, Artur Jurczyszyn, Alicja Dębska-Ślizień, Jeremy R. Chapman, Pierre Ronco, Hatem Amer, Germaine Wong, Yang Li, Petra Tesarova, and KAZANCIOĞLU, RÜMEYZA
Subjects: 0301 basic medicine, Nephrology, medicine.medical_specialty, renal cell carcinoma, Palliative care, glomerular filtration rate, nephrotoxicity, oncology, 030232 urology & nephrology, Pharmacy, Malignancy, law.invention, 03 medical and health sciences, 0302 clinical medicine, law, Internal medicine, medicine, Intensive care medicine, Clinical pharmacology, business.industry, Cancer, medicine.disease, 030104 developmental biology, business, Kidney cancer, Kidney disease
Abstract: © 2020 Kidney Disease:Improving Global Outcomes (KDIGO)The association between kidney disease and cancer is multifaceted and complex. Persons with chronic kidney disease (CKD) have an increased incidence of cancer, and both cancer and cancer treatments can cause impaired kidney function. Renal issues in the setting of malignancy can worsen patient outcomes and diminish the adequacy of anticancer treatments. In addition, the oncology treatment landscape is changing rapidly, and data on tolerability of novel therapies in patients with CKD are often lacking. Caring for oncology patients has become more specialized and interdisciplinary, currently requiring collaboration among specialists in nephrology, medical oncology, critical care, clinical pharmacology/pharmacy, and palliative care, in addition to surgeons and urologists. To identify key management issues in nephrology relevant to patients with malignancy, KDIGO (Kidney Disease: Improving Global Outcomes) assembled a global panel of multidisciplinary clinical and scientific expertise for a controversies conference on onco-nephrology in December 2018. This report covers issues related to kidney impairment and solid organ malignancies as well as management and treatment of kidney cancer. Knowledge gaps, areas of controversy, and research priorities are described.
Published: 2020

45. HLA class II alleles differing by a single amino acid associate with clinical phenotype and outcome in patients with primary membranous nephropathy

Author: Hanna Debiec, Pierre Ronco, Li-qiang Meng, Ming-Hui Zhao, Fang Wang, Hong Zhang, Zhao Cui, Xu-yang Cheng, Li-jie Zhang, Yi-miao Zhang, Gang Liu, Zhen Qu, Zhi-yong Pei, Huai-yu Wang, Xu-jie Zhou, Jing Huang, Fang-jin Chen, Xin Wang, Li-jun Xie, Laboratoire Traitement et Communication de l'Information (LTCI), Télécom ParisTech-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), China Agriculture University [Beijing], Centre de Géosciences (GEOSCIENCES), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), China Agricultural University (CAU), 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], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Nanjing University of Science and Technology (NJUST), RONCO, Pierre, Peking University [Beijing], Renal Division [Beijing, China], Beijing Computing Center [Beijing, China], Beijing National Laboratory for Molecular Sciences (BNLMS), Beihang University (BUAA), Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Tsinghua-Peking Joint Center for Life Sciences, and Tsinghua University [Beijing] (THU)
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, 030232 urology & nephrology, Renal function, Human leukocyte antigen, Glomerulonephritis, Membranous, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, Genotype, medicine, Humans, Risk factor, ComputingMilieux_MISCELLANEOUS, Alleles, Aged, Autoantibodies, Proportional Hazards Models, Kidney, business.industry, Receptors, Phospholipase A2, Hazard ratio, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Molecular Docking Simulation, Phenotype, 030104 developmental biology, medicine.anatomical_structure, Nephrology, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, business, HLA-DRB1 Chains
Abstract: Genome-wide associations and HLA genotyping have revealed associations between HLA alleles and susceptibility to primary membranous nephropathy. However, associations with clinical phenotypes and kidney outcome are poorly defined. We previously identified DRB1*1501 and DRB1*0301 as independent risk alleles for primary membranous nephropathy. Here, we investigated HLA associations with demographic characteristics, anti-phospholipase A2 receptor (PLA2R) antibody, treatment response and kidney outcome after a median follow-up of 52 months in 258 patients. DRB1*0301, but not DRB1*1501, was associated with a significantly higher level of PLA2R antibody (odds ratio 1.58, 95% confidence interval 1.13-2.22). Although DRB1*1502, which differs from DRB1*1501 by a single amino acid, was not a risk allele for primary membranous nephropathy (odds ratio 1.01), it was associated with significantly lower estimated glomerular filtration rates both at baseline (1.79, 1.18-2.72) and at last follow-up (1.72, 1.17-2.53), a significantly worse renal outcome by Kaplan-Meier analysis and a significantly higher risk of end-stage renal disease by Cox regression analysis (hazard ratio 4.52, 1.22-16.74). Nevertheless, the absence of remission remained the only independent risk factor for end-stage renal disease by multivariate analysis. DRB1*1502 was also associated with a significantly higher median PLA2R antibody level [161.4 vs. 36.3 U/mL] and showed interaction with DRB1*0301 for this variable. Thus, HLA genes control PLA2R antibody production and primary membranous nephropathy severity and outcome. Additionally, DRB1*1502 behaves like a modifier gene with a strong predictor value when associated with HLA risk alleles. Other modifier genes need further investigations in larger cohorts.
Published: 2018

46. Clearance of carbapenem-resistant Enterobacteriaceae vs vancomycin-resistant enterococci carriage after faecal microbiota transplant: a prospective comparative study

Author: Lélia Escaut, B. Davido, R. Lepeule, Daniel Vittecoq, C. Lawrence, H. Michelon, Frédérique Bouchand, Clara Duran, F. Chast, I. Sobhani, H. Fessi, Rui Batista, Pierre Ronco, A. Dinh, Laboratoire d'automatique et de génie des procédés (LAGEP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Hôpital Raymond Poincaré [AP-HP], Service de Maladies Infectieuses et Tropicales [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies Infectieuses et Tropicales [CHU Raymond Poincaré], Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Adult, Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Adolescent, Drug-Related Side Effects and Adverse Reactions, medicine.drug_class, medicine.medical_treatment, 030106 microbiology, Antibiotics, Carbapenem-resistant enterobacteriaceae, Polymerase Chain Reaction, Vancomycin-Resistant Enterococci, Feces, Young Adult, 03 medical and health sciences, Interquartile range, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, medicine, Humans, Colonization, Prospective Studies, Adverse effect, Gram-Positive Bacterial Infections, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Bacteriological Techniques, business.industry, Enterobacteriaceae Infections, Immunosuppression, General Medicine, Fecal Microbiota Transplantation, Middle Aged, biochemical phenomena, metabolism, and nutrition, 3. Good health, Carbapenem-Resistant Enterobacteriaceae, Treatment Outcome, Infectious Diseases, Carriage, Concomitant, Carrier State, Female, business
Abstract: Summary Background Carbapenem-resistant Enterobacteriaceae (CRE) and vancomycin-resistant enterococci (VRE) carriage are increasing worldwide. Faecal microbiota transplantation (FMT) appears to be an attractive option for decolonization. This study aimed to evaluate CRE vs VRE clearance by FMT among carriers. Methods A multi-centre trial was undertaken on patients with CRE or VRE digestive tract colonization who received FMT between January 2015 and April 2017. Adult patients with CRE or VRE colonization, confirmed by three consecutive rectal swabs at weekly intervals, including one in the week prior to FMT, were included in the study. Patients with immunosuppression or concomitant antibiotic prescription at the time of FMT were excluded. Successful decolonization was determined by at least two consecutive negative rectal swabs [polymerase chain reaction (PCR) and culture] on Days 7, 14, 21 and 28, and monthly for three months following FMT. Results Seventeen patients were included, with a median age of 73 years [interquartile range (IQR) 64.3–79.0]. Median duration of carriage of CRE or VRE before FMT was 62.5 days (IQR 57.0–77.5). One week after FMT, three of eight patients were free of CRE colonization and three of nine patients were free of VRE colonization. After three months, four of eight patients were free of CRE colonization and seven of eight patients were free of VRE colonization. Qualitative PCR results were concordant with culture. Six patients received antibiotics during follow-up, three in each group. No adverse events were reported. Conclusion CRE and VRE clearance rates were not significantly different in this study, possibly due to the small sample size, but a trend was observed. These data should be confirmed by larger cohorts and randomized trials.
Published: 2018

47. Transethnic, Genome-Wide Analysis Reveals Immune-Related Risk Alleles and Phenotypic Correlates in Pediatric Steroid-Sensitive Nephrotic Syndrome

Author: Elisabet Ars, Claire Dossier, José Ballarín, Stéphanie Debette, Pierre Ronco, Eric Letouzé, Hanna Debiec, Tabassome Simon, Siham Chafai Elalaoui, Matthias Kretzler, Georges Deschênes, Marina Vivarelli, Manuela Colucci, Valery Elie, Matthew G. Sampson, Philippe Amouyel, Evelyne Jacqz-Aigrain, Christopher E. Gillies, Valérie Dubois, Francesco Emma, Abdelaziz Sefiani, Rosemary K B Putler, 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 de Néphrologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe labellisée Ligue contre le Cancer, Labex Immuno-oncology, Université Paris Descartes - Paris 5 (UPD5)-PRES Sorbonne Paris Cité, Unité de Formation et de Recherche Santé, Médecine, Biologie Humaine [Bobigny], Université Paris 13 (UP13)-Sorbonne Paris Cité, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Pediatric Nephrology [Ann Arbor, MI, USA] (School of Medicine), University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Nephrology and Dialysis Department [Rome, Italy], Istituto di Ricovero e Cura a Carattere Scientifico Ospedale Pediatrico Bambino Gesù [Rome, Italy], Molecular Biology Laboratory [Barcelona, Spain] (Fundació Puigvert - UAB), Universitat Autònoma de Barcelona (UAB)-Instituto de Investigaciones Biomédicas Sant Pau [Barcelona, Spain]-Fundació Puigvert [Barcelona, Spain], Centre d'Investigation Clinique 1426 (CIC 1426), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Department of Medical Genetics [Rabat, Morocco], Institut National d’Hygiène [Rabat, Morocco], Human Genomic Center [Rabat, Morocco], Université Mohamed V - Souissi, Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche Clinique de l’Est Parisien [CHU Saint-Antoine] (URC-EST), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-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)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Internal Medicine and Computational Medicine and Bioinformatics [Ann Arbor, MI, USA], Department of Nephrology [Barcelona, Spain], Fundación Puigvert [Barcelona, Spain], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), 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), This study was funded by European Research Council grant ERC-2012- ADG_20120314 (grant agreement 322947) and Agence Nationale pour la Recherche 'Genetransnephrose' grant ANR-16-CE17-004-01. M.G.S. is supported by the Charles Woodson Clinical Research Fund and National Institutes of Health grant R01-DK108805. The Nephrotic Syndrome Study Network Consortium (NEPTUNE, U54-DK-083912) is a part of the National Center for Advancing Translational Sciences (NCATS) Rare Disease Clinical Research Network (RDCRN) supportedthrough a collaboration between the Office of Rare Diseases Research(ORDR), the NCATS, and the National Institute of Diabetes, Digestive,and Kidney Diseases. The RDCRN is an initiative of the ORDR of theNCATS. Additional funding and/or programmatic support for thisproject has also been provided by the University of Michigan, NephCureKidney International, and the Halpin Foundation. The NEPHROVIRcohort has been supported by two grants from the Programme Hospitalier de Recherche Clinique: grants PHRC 2007-AOM07018 and PHRC 2011-AOM11002. The NEPHROVIR network is coordinated by the Pediatric Nephrology Unit of Robert Debré Hospital, the 'Unité de Recherche Clinique de l’Est Parisien,' and the 'Délégation de la Recherche Clinique de la Région Ile-de-France.' M.V. and M.C. are supported by the Associazone per la Cura del bambino Nefropatico Organizzazione Non Lucrativa di Utilità Sociale., Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Universitat Autònoma de Barcelona (UAB)-Fundació Puigvert [Barcelona, Spain]-Instituto de Investigaciones Biomédicas Sant Pau [Barcelona, Spain], Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Mohammed V de Rabat [Agdal] (UM5), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-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)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Direction de la Recherche Clinique et de l'Innovation [AP-HP] (DRCI), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Département de Néphrologie = Service de Néphrologie et Dialyses [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), and RONCO, Pierre
Subjects: Male, 0301 basic medicine, 030232 urology & nephrology, Genome-wide association study, Cohort Studies, 0302 clinical medicine, Africa, Northern, HLA-DQ beta-Chains, Medicine, Child, Genetics, nephrotic syndrome, genetic renal disease, General Medicine, Phenotype, Italy, Nephrology, Child, Preschool, Cohort, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Steroids, France, pediatrics, Quantitative Trait Loci, Black People, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, White People, 03 medical and health sciences, HLA-DQ Antigens, Up Front Matters, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, SNP, Allele, Alleles, Genetic association, focal segmental glomerulosclerosis, genome-wide association study, Butyrophilins, business.industry, HLA-DR Antigens, Genetic architecture, HLA-DRB5 Chains, 030104 developmental biology, Spain, Case-Control Studies, Expression quantitative trait loci, gene expression, business, HLA-DRB1 Chains
Abstract: Background Steroid-sensitive nephrotic syndrome (SSNS) is a childhood disease with unclear pathophysiology and genetic architecture. We investigated the genomic basis of SSNS in children recruited in Europe and the biopsy-based North American NEPTUNE cohort. Methods We performed three ancestry-matched, genome-wide association studies (GWAS) in 273 children with NS (Children Cohort Nephrosis and Virus [NEPHROVIR] cohort: 132 European, 56 African, and 85 Maghrebian) followed by independent replication in 112 European children, transethnic meta-analysis, and conditional analysis. GWAS alleles were used to perform glomerular cis -expression quantitative trait loci studies in 39 children in the NEPTUNE cohort and epidemiologic studies in GWAS and NEPTUNE (97 children) cohorts. Results Transethnic meta-analysis identified one SSNS-associated single-nucleotide polymorphism (SNP) rs1063348 in the 3′ untranslated region of HLA-DQB1 ( P =9.3×10 −23 ). Conditional analysis identified two additional independent risk alleles upstream of HLA-DRB1 (rs28366266, P =3.7×10 −11 ) and in the 3′ untranslated region of BTNL2 (rs9348883, P =9.4×10 −7 ) within introns of HCG23 and LOC101929163 . These three risk alleles were independent of the risk haplotype DRB1*07:01-DQA1*02:01-DQB1*02:02 identified in European patients. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS. Increased burden of risk alleles across independent loci was associated with higher odds of SSNS, with younger age of onset across all cohorts, and with increased odds of complete remission across histologies in NEPTUNE children. rs1063348 associated with decreased glomerular expression of HLA-DRB1, HLA-DRB5, and HLA-DQB1. Conclusions Transethnic GWAS empowered discovery of three independent risk SNPs for pediatric SSNS. Characterization of these SNPs provide an entry for understanding immune dysregulation in NS and introducing a genomically defined classification.
Published: 2018

48. Acidic organelles mediate TGF-β1-induced cellular fibrosis via (pro)renin receptor and vacuolar ATPase trafficking in human peritoneal mesothelial cells

Author: Sadayoshi Ito, Yoshikazu Muroya, Yusuke Ohsaki, Kazuhito Totsune, Ikuko Oba-Yabana, Takuo Hirose, Rémi Piedagnel, Chika Takahashi, Satoshi Kinugasa, Emiko Sato, Pierre Ronco, Takefumi Mori, Genevieve Nguyen, Tohoku University [Sendai], Centre interdisciplinaire de recherche en biologie (CIRB), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Collège de France (CdF)-PSL Research University (PSL), AGroécologie, Innovations, teRritoires (AGIR), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), 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 [APHP], Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Université Pierre et Marie Curie - Paris 6 (UPMC), 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), École normale supérieure - Paris (ENS-PSL), 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-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), Service d'Urgences néphrologiques et transplantation rénale [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), and HAL UPMC, Gestionnaire
Subjects: Male, MAPK/ERK pathway, 030232 urology & nephrology, lcsh:Medicine, 030204 cardiovascular system & hematology, Pharmacology, Kidney, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Epithelium, chemistry.chemical_compound, 0302 clinical medicine, Cell Movement, Fibrosis, Dialysis Solutions, Renin, Receptor, lcsh:Science, Peritoneal Cavity, Peritoneal Fibrosis, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, Methylglyoxal, Hydrogen-Ion Concentration, Middle Aged, Protein Transport, Female, Peritoneum, Peritoneal Dialysis, Vacuolar Proton-Translocating ATPases, Receptors, Cell Surface, Article, Transforming Growth Factor beta1, 03 medical and health sciences, Downregulation and upregulation, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Renin–angiotensin system, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Rats, Wistar, Aged, Organelles, lcsh:R, Kidney metabolism, medicine.disease, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Rats, Glucose, chemistry, lcsh:Q
Abstract: TGF-β1, which can cause renal tubular injury through a vacuolar-type H+-ATPase (V-ATPase)-mediated pathway, is induced by the glucose degradation product methylglyoxal to yield peritoneal injury and fibrosis. The present study investigated the roles of V-ATPase and its accessory protein, the (pro)renin receptor, in peritoneal fibrosis during peritoneal dialysis. Rats daily administered 20 mM methylglyoxal intraperitoneally developed significant peritoneal fibrosis after 7 days with increased expression of TGF-β and V-ATPase, which was reduced by the inhibition of V-ATPase with co-administration of 100 mM bafilomycin A1. The (pro)renin receptor and V-ATPase were expressed in acidic organelles and cell membranes of human peritoneal mesothelial cells. TGF-β1 upregulated the expression of collagens, α-SMA, and EDA-fibronectin, together with ERK1/2 phosphorylation, which was reduced by inhibition of V-ATPase, (pro)renin receptor, or the MAPK pathway. Fibronectin and the soluble (pro)renin receptor were excreted from cells by acidic organelle trafficking in response to TGF-β1; this excretion was also suppressed by inhibition of V-ATPase. Soluble (pro)renin receptor concentrations in effluents of patients undergoing peritoneal dialysis were associated with the dialysate-to-plasma ratio of creatinine. Together, these results demonstrate a novel fibrosis mechanism through the (pro)renin receptor and V-ATPase in the acidic organelles of peritoneal mesothelial cells.
Published: 2018

49. Membranous Nephropathy and Intrarenal Extramedullary Hematopoiesis in a Patient With Myelofibrosis

Author: Pierre Ronco, Carole Philipponnet, Julien Aniort, Jean-Louis Kemeny, and Anne-Elisabeth Heng
Subjects: Male, Pathology, medicine.medical_specialty, Nephrotic Syndrome, 030232 urology & nephrology, Renal function, Antineoplastic Agents, Kidney, Glomerulonephritis, Membranous, 03 medical and health sciences, 0302 clinical medicine, Membranous nephropathy, Nitriles, medicine, Edema, Humans, Hydroxyurea, Myelofibrosis, urogenital system, business.industry, Glomerulonephritis, Acute Kidney Injury, Middle Aged, medicine.disease, Extramedullary hematopoiesis, Pyrimidines, medicine.anatomical_structure, Primary Myelofibrosis, Nephrology, Hematopoiesis, Extramedullary, 030220 oncology & carcinogenesis, Pyrazoles, business, Nephrotic syndrome, Kidney disease
Abstract: Kidney disease in the setting of a hematologic malignancy is common, with the frequency and type of kidney disease varying depending on the specific malignancy. Various glomerular diseases and tumor infiltration of the kidneys have been reported in patients with lymphoproliferative disorders. Descriptions of kidney involvement in myeloproliferative disorders have been much rarer. We report a case of membranous nephropathy accompanied by kidney injury in a patient with primary myelofibrosis with additional features considered related to the patient's myeloproliferative disorder. A 63-year-old patient with primary myelofibrosis underwent kidney biopsy to investigate nephrotic-range proteinuria and reduced kidney function. Histologic analysis revealed mesangial sclerosis and hypercellularity, changes indicative of membranous nephropathy, and infiltration of hematopoietic cells into the renal interstitium, peritubular capillaries, and perirenal tissue consistent with extramedullary hematopoiesis. He was treated with renin-angiotensin blockade and a Janus kinase inhibitor, resulting in improvement in kidney function and proteinuria.
Published: 2017

50. Corrigendum to Berchtold L, Letouzé E, Alexander MP, et al. HLA-D and PLA2R1 risk alleles associate with recurrent primary membranous nephropathy in kidney transplant recipients. Kidney Int. 2021;99:671–685

Author: Valérie Dubois, Eric Letouzé, Paul Brenchley, Christophe Legendre, Pierre Ronco, Philippe Rieu, Manish J. Gandhi, Hanna Debiec, Vincent Vuiblet, Maryvonne Hourmant, Petra Mrázová, Sylvain Guibert, Ann M. Moyer, Guillaume Canaud, Jack F.M. Wetzels, Anne Els van de Logt, José Aurelio Ballarín Castan, Christiane Mousson, Patrick Hamilton, Nadhir Yousfi, Charlène Levi, Mariam P. Alexander, Ondřej Viklický, B. Moulin, Gabriel Choukroun, Lena Berchtold, Armando Torres, Josep M. Cruzado, and Vladimir Tesar
Subjects: Kidney, medicine.medical_specialty, business.industry, INT, medicine.disease, Gastroenterology, Kidney transplant, medicine.anatomical_structure, Membranous nephropathy, Nephrology, Internal medicine, Risk allele, medicine, business
Published: 2021

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

361 results on '"Pierre, Ronco"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources