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

Area of Science:

• Nephrology
• Complement Biology
• Clinical Trial Endpoints

Background:

• C3 glomerulopathy (C3G) and primary immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) are rare kidney diseases driven by complement dysregulation.
• Proteinuria is a common clinical endpoint in trials for these conditions but lacks broad regulatory validation despite its prognostic value for kidney failure.
• Establishing consensus on proteinuria's role is crucial for advancing treatment strategies.

Purpose of the Study:

• To establish expert consensus on the clinical relevance of proteinuria as a prognostic and treatment end point in C3G and primary IC-MPGN.
• To determine the value of proteinuria reduction as a surrogate biomarker for kidney function preservation in these rare glomerular diseases.

Main Methods:

• A 2-round modified Delphi process involving literature review and expert input.
• A steering committee developed 31 statements across three domains: treatment efficacy, current assessment, and the role of proteinuria.
• Statements were surveyed online using a 4-point Likert scale among European nephrologists and kidney pathologists.

Main Results:

• Consensus (≥75% agreement) was reached on 29 out of 31 statements.
• Key findings include: proteinuria reduction preserves long-term kidney function and is a treatment goal.
• A ≥50% reduction in proteinuria over 6 months indicates therapeutic benefit, and proteinuria <1 g/d is linked to better outcomes.

Conclusions:

• Expert consensus supports proteinuria as a meaningful treatment end point for C3G and primary IC-MPGN.
• Longitudinal monitoring of proteinuria aids in guiding treatment decisions for these complement-mediated kidney diseases.
• Proteinuria serves as a valuable surrogate biomarker for assessing treatment efficacy and predicting long-term kidney outcomes.