Association between early proteinuria reduction and kidney outcomes in Japanese patients with IgA nephropathy: The Japan Chronic Kidney Disease Database

Proteinuria reduction is an established surrogate endpoint for IgA nephropathy (IgAN) progression in international trials, but evidence in Japanese populations is scarce. We aimed to assess the association between early changes in proteinuria and long-term kidney outcomes in a large, real-world cohort of Japanese patients with IgAN.

This nationwide, multicenter cohort study utilized the Japan Chronic Kidney Disease Database (J-CKD-DB) data. We analyzed 1,039 IgAN patients (mean age 48.8 years; 46.0% women), categorized by dipstick proteinuria change at 9 ± 1 months from baseline: a reduction group (≥1-step improvement) and a non-reduction group (stable or worsened). The primary outcome was total eGFR slope; secondary was a composite kidney event (≥40% eGFR decline or eGFR < 15 mL/min/1.73 m²).

The mean baseline eGFR was 56.8 (±27.7) mL/min/1.73 m². During a median follow-up of 1,357 days, the mean annual eGFR slope in the reduction group was -0.13 mL/min/1.73 m² (95% CI, -0.37 to 0.11), compared to -2.73 mL/min/1.73 m² (95% CI, -2.96 to -2.49) in the non-reduction group. In multivariable adjustment for baseline covariates, the hazard ratio for the composite kidney event in the reduction group was significantly lower compared to the non-reduction group was 0.79 (95% CI, 0.63-0.99).

In this large, real-world Japanese cohort, early dipstick proteinuria reduction was significantly associated with both a slower long-term eGFR decline and a lower risk of major kidney events. These findings may support the use of early proteinuria reduction as a surrogate endpoint for clinical trials and regulatory evaluation of IgA nephropathy in Japan.