C3糸球体症および原発性免疫複合体介在性膜性増殖性糸球体腎炎における代替エンドポイントに関するデルファイコンセンサス

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.