Supportive Evidence of Surrogate End Points Based on Treatment Effect of Corticosteroid in IgA Nephropathy.

Introduction: Estimated glomerular filtration rate (eGFR) slope and proteinuria reduction have been proposed as surrogate end points for kidney outcomes in IgA nephropathy (IgAN), but their validity remains under debate. We aimed to evaluate the surrogate potential of these markers in the context of corticosteroid therapy within a large Japanese cohort. Methods: Patients with biopsy-proven IgAN from the Japan IgA Nephropathy Cohort Study were analyzed. Patients were categorized based on corticosteroid exposure within 12 months of diagnosis. To minimize confounding, overlap weighting was used to balance baseline characteristics. The primary outcome was a composite kidney end point defined as a ≥ 40 decline in eGFR or the initiation of kidney replacement therapy. Secondary outcomes included 2-year eGFR slope and proteinuria reduction at 1-year. Results: Corticosteroid therapy was associated with a lower incidence of the composite kidney outcome (5.3 vs. 13.1%, P = 0.0485), slower decline in eGFR (-0.32 vs. -2.95 ml/min per 1.73 m2/yr, P = 0.01), and greater proteinuria reduction (-76.5% vs. -48.0%, P < 0.001). Conclusion: Both the eGFR slope and proteinuria reduction demonstrated strong and consistent associations with kidney outcomes in the context of corticosteroid therapy. These findings support their effectiveness as surrogate end points for clinical trials and suggest their usefulness for risk stratification and therapeutic monitoring in routine nephrology practice.