Nicolas Hanset1, Selda Aydin2, Nathalie Demoulin1, Jean-Pierre Cosyns2, Diego Castanares-Zapatero3, Ralph Crott4, Jean-François Cambier5, Jean-Michel Pochet6, Gaëlle Gillerot7, Francois Reginster8, Frédéric Houssiau9, Hanna Debiec10, Pierre Ronco11, Michel Jadoul1, Johann Morelle12. 1. Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium. 2. Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium; Department of Pathology, Cliniques universitaires Saint-Luc, Brussels, Belgium. 3. Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium. 4. Consultant in Biostatistics, Colombiers, France. 5. Department of Nephrology, Grand Hôpital de Charleroi, Gilly, Belgium. 6. Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium; Centre Hospitalier Universitaire UCLouvain-Namur, Namur, Belgium. 7. Clinique Saint-Pierre, Ottignies, Belgium. 8. Cliniques de l'Europe, Brussels, Belgium. 9. Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium; Division of Rheumatology, Cliniques universitaires Saint-Luc, Brussels, Belgium. 10. Sorbonne Université, Université Pierre et Marie Curie Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, Paris, France. 11. Sorbonne Université, Université Pierre et Marie Curie Paris 06, Paris, France; Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital de Jour de Néphrologie, Hôpital Tenon, Paris, France. 12. Division of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium; Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium. Electronic address: johann.morelle@uclouvain.be.
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.
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.
Authors: Sanjeev Sethi; Benjamin Madden; Hanna Debiec; Johann Morelle; M Cristine Charlesworth; LouAnn Gross; Vivian Negron; David Buob; Sidharth Chaudhry; Michel Jadoul; Fernando C Fervenza; Pierre Ronco Journal: J Am Soc Nephrol Date: 2021-04-08 Impact factor: 10.121
Authors: Michèle Saïdi; Isabelle Brochériou; Emmanuel Estève; Sophie Tuffet; Zahir Amoura; Makoto Miyara; Xavier Belenfant; Tim Ulinski; Philippe Rouvier; Hanna Debiec; Pierre Ronco; David Buob Journal: Kidney Int Rep Date: 2021-05-05