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    المساهمون: 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), UCL - SSS/IREC - Institut de recherche expérimentale et clinique

    المصدر: American journal of kidney diseases, Vol. 76, no. 5, p. 624-635 (2020)
    American Journal of Kidney Diseases
    American Journal of Kidney Diseases, 2020, 76 (5), pp.624-635. ⟨10.1053/j.ajkd.2020.04.013⟩
    American journal of kidney diseases : the official journal of the National Kidney Foundation, (2020)

    الوصف: 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.

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