Clinical Trials Logo

Clinical Trial Summary

Membranous Nephropathy (MN) is an auto-immune kidney disease and a common cause of nephrotic syndrome. About 30% of MN patients progress to end-stage kidney disease (ESKD) while 30% undergo spontaneous remission. The phospholipase A2 receptor (PLA2R1) is the major auto-antigen in idiopathic MN. Anti-PLA2R1 autoantibodies are found during the active phase of MN. Predictors of disease progression include high titers of anti-PLA2R1 autoantibodies and serum creatinine levels at presentation, as well as decline in renal function during the first six months of follow-up. Investigators identified new prognostic factors in a cohort of 41 idiopathic MN patients with nephrotic syndrome and anti-PLA2R1 autoantibodies at the time of presentation. During a follow-up of at least 36 months, 21 patients had a persistent nephrotic syndrome (group A) and 20 showed partial or total remission (group R). We first measured the cross-reactivity of their sera at the time of presentation to human, rabbit and mouse recombinant PLA2R1 by western blot. All patients exhibited reactivity against human and rabbit PLA2R1, but only some of them did against mouse PLA2R1. These results suggest the presence of distinct epitopes that are differentially conserved among PLA2R1 orthologs.Investigators then set-up three parallel ELISAs using human, rabbit and mouse recombinant PLA2R1. All 41 MN patients showed activity in human and rabbit ELISAs at presentation but only 32 of them (78%) in mouse ELISA.They finally analyzed the association between anti-PLA2R1 titers at presentation in the different ELISAs and the subsequent clinical outcome. The mean anti-PLA2R1 activity was significantly different between group A and R in mouse ELISA but not in human and rabbit ELISA. Patients with anti-mouse PLA2R1 activity over 605 RU (relative unit)/ml showed a significantly lower survival without doubling of serum creatinine or ESKD , but patients in the highest tertile of anti-PLA2R1 activity in rabbit and human ELISA did not show a significant increased risk of renal failure progression. The results suggest that the specific detection of particular anti-PLA2R1 autoantibodies using the novel anti-mouse PLA2R1 ELISA can identify MN patients at risk for ESKD. The aim is to confirm these result on a prospective cohort.


Clinical Trial Description

Membranous Nephropathy (MN) is an auto-immune kidney disease and a common cause of nephrotic syndrome. About 30% of MN patients progress to end-stage kidney disease (ESKD) while 30% undergo spontaneous remission. The phospholipase A2 receptor (PLA2R1) is the major auto-antigen in idiopathic MN. Anti-PLA2R1 autoantibodies are found during the active phase of MN [2,3]. Predictors of disease progression include high titers of anti-PLA2R1 autoantibodies and serum creatinine levels at presentation, as well as decline in renal function during the first six months of follow-up. Investigators identified new prognostic factors in a cohort of 41 idiopathic MN patients with nephrotic syndrome and anti-PLA2R1 autoantibodies at the time of presentation. During a follow-up of at least 36 months, 21 patients had a persistent nephrotic syndrome (group A) and 20 showed partial or total remission (group R). We first measured the cross-reactivity of their sera at the time of presentation to human, rabbit and mouse recombinant PLA2R1 by western blot. All patients exhibited reactivity against human and rabbit PLA2R1, but only some of them did against mouse PLA2R1. These results suggest the presence of distinct epitopes that are differentially conserved among PLA2R1 orthologs. We then set-up three parallel ELISAs using human, rabbit and mouse recombinant PLA2R1. All 41 MN patients showed activity in human and rabbit ELISAs at presentation but only 32 of them (78%) in mouse ELISA. Investigators finally analyzed the association between anti-PLA2R1 titers at presentation in the different ELISAs and the subsequent clinical outcome. The mean anti-PLA2R1 activity was significantly different between group A and R in mouse ELISA in both univariate and multivariate analyses (p =0.006 and p =0.02, respectively) but not in human and rabbit ELISAs. An analysis of the mouse ELISA titers defines a threshold of 605 RU/ml above which 100% of patients had a poor prognosis, but no such threshold could be defined in rabbit and human ELISA. Patients with anti-mouse PLA2R1 activity over 605 RU/ml showed a significantly lower survival without doubling of serum creatinine or ESKD (p=0.002 using the log-rank test), but patients in the highest tertile of anti-PLA2R1 activity in rabbit and human ELISAs did not show a significant increased risk of renal failure progression. The results suggest that the specific detection of particular anti-PLA2R1 autoantibodies using the novel anti-mouse PLA2R1 ELISA can identify MN patients at risk for ESKD. The aim is to confirm these result on a prospective cohort.We propose to measure on a prospective cohort at the time of MN diagnosis if high titer of anti-mPLA2R1 Ab (anti-mouse phospholipase A2 receptor1 antibodies) is associated with nephrotic proteinuria (over 3.5 g/g) or increased of creatininemia over 30% at month 6, 12 and 18. An ancillary study will try to characterised the nephrogenic epitope conserved between human, rabbit and mouse. Each patient with nephrotic syndrome should benefit of a kidney biopsy. For each patient we will conserved 2 dry tubes frozen at the time of biopsy. If we confirm the diagnosis of MN with anti-PLA2R1 Ab, we propose to the patient to be included in this study. He will have a visit every months for the first three months and every three months after, with collection of the following: blood pressure, weight, creatinine, albumin, blood electrolytes, proteinuria / creatinine in sample 1 assay Ac anti-PLA2R1 on 3 ELISA (human, rabbit and mouse) In case of persistent refractory nephrotic syndrome after 6 months, or the appearance of a 30% increase in serum creatinine, treatment with rituximab (2 × 1 g IV 15 days) will be proposed. Clinical and biological monitoring will be continued every 3 months for 18 months. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT02199145
Study type Interventional
Source Centre Hospitalier Universitaire de Nice
Contact
Status Completed
Phase N/A
Start date July 17, 2015
Completion date June 4, 2020

See also
  Status Clinical Trial Phase
Recruiting NCT04095156 - Autoreactive B Cells in Membranous Nephropathy
Not yet recruiting NCT06341205 - Personalized Rituximab Treatment Based on Artificial Intelligence in Membranous Nephropathy (iRITUX) Phase 3
Active, not recruiting NCT04893096 - MOR202 for Refractory MN Phase 2
Completed NCT00405340 - Rituximab in the Treatment of Idiopathic Membranous Nephropathy Phase 0
Recruiting NCT06065852 - National Registry of Rare Kidney Diseases
Active, not recruiting NCT04652570 - Efficacy and Safety of VB119 in Subjects With Membranous Nephropathy Phase 1/Phase 2
Not yet recruiting NCT06242327 - An Outcome Analysis of Primary Membranous Nephropathy
Recruiting NCT03929887 - KOrea Renal Biobank NEtwoRk System TOward NExt-generation Analysis
Active, not recruiting NCT03949855 - Belimumab With Rituximab for Primary Membranous Nephropathy Phase 2
Completed NCT00983034 - The Effects of Helicobacter Pylori Eradication on Proteinuria in Patients With Membranous Nephropathy N/A
Completed NCT03025828 - Adrenocorticotropic Hormone in Membranous Nephropathy Phase 4
Recruiting NCT05732402 - An Open-label Study of Povetacicept (ALPN-303) in Autoimmune Kidney Diseases Phase 1/Phase 2
Enrolling by invitation NCT04571658 - NEPTUNE Match Study
Active, not recruiting NCT05894512 - Analysis of T- and B-Cell Subpopulations in Membranous Nephropathy
Not yet recruiting NCT05941845 - Interferon Alfa Therapy Based on Th17 Profile in Membranous Nephropathy Phase 2
Completed NCT00518219 - To Compare the Efficacy and Safety of Tripterygium Wilfordii (TW) Versus Valsartan in the Membranous Nephropathy (MN) Phase 4
Not yet recruiting NCT04326218 - Immunopathological Analysis in a French National Cohort of Membranous Nephropathy N/A
Active, not recruiting NCT03453619 - Phase II Study Assessing Safety and Efficacy of APL-2 in Glomerulopathies Phase 2
Completed NCT01955187 - Sequential Therapy With Tacrolimus and Rituximab in Primary Membranous Nephropathy Phase 3
Completed NCT04733040 - Efficacy, Safety and PK/PD of MOR202 in Anti-PLA2R + Membranous Nephropathy (aMN) (NewPLACE) Phase 2