Delphi Consensus on Surrogate End Points in C3 Glomerulopathy and Primary Immune Complex-Mediated...

C3 glomerulopathy (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) are rare kidney diseases driven by complement dysregulation. Proteinuria is a commonly used clinical end point in trials involving these conditions. However, its recognition as a validated end point by regulatory bodies remains limited, despite growing evidence supporting its prognostic value as a surrogate biomarker for the development of kidney failure. The aim of this study was to establish consensus on the clinical relevance of proteinuria as a prognostic and treatment end point in C3G and primary IC-MPGN.

A 2-round modified Delphi process was conducted, informed by literature review and expert input. A steering committee composed of 4 European nephrologists, 1 Canadian nephrologist, and 1 European rheumatologist developed 31 statements covering the following 3 domains: (i) treatment efficacy end points, (ii) current assessment end points, and (iii) the role of proteinuria. Statements formed part of an online survey using a 4-point Likert scale, distributed to a broader panel of nephrologists and kidney pathologists across Europe.

Fifty-one and 50 responses were received in rounds 1 and 2. Of the 31 statements, 29 reached consensus (≥ 75% agreement). Key consensus points included the following: (i) reduction in proteinuria preserves long-term kidney function and is a treatment goal; (ii) longitudinal monitoring of proteinuria, alongside other markers is valuable for guiding treatment; (iii) a ≥ 50% proteinuria reduction over 6 months indicates meaningful therapeutic benefit; and (iv) proteinuria < 1 g/d is associated with improved outcomes.

This study demonstrates consensus supporting proteinuria as a meaningful treatment end point for C3G and primary IC-MPGN.