Clinical Trial: Role of Anti-mouse PLA2R1 ELISA in Membranous Nephropathy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Indication and Response to Immunosuppressive Treatment in Membranous Nephropathy : Role of Anti-mouse PLA2R1 ELISA

Brief 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

Detailed 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 [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
Sponsor: Centre Hospitalier Universitaire de Nice

Current Primary Outcome: Change from baseline Creatininemia level [ Time Frame: at 6, 12 and 18 months ]

30% increase in creatininemia after 6 months of symptomatic treatment with RAAS blocker


Original Primary Outcome: Same as current

Current Secondary Outcome: Remission rate in MN [ Time Frame: at 12 months ]

Remission rate in MN one year after Rituximab with absence of nephrotic syndrome and renal insufficiency (estimated by MDRD> 60 ml/min/1, 73m2).

(MDRD=Modification of the Diet in Renal Disease)



Original Secondary Outcome: Same as current

Information By: Centre Hospitalier Universitaire de Nice

Dates:
Date Received: July 22, 2014
Date Started: July 2015
Date Completion: October 2017
Last Updated: September 29, 2015
Last Verified: September 2015