# Proteinuria reduction as a surrogate endpoint for clinical study of IgA nephropathy in Japanese patients: data from the J-CKD-DB-Ex

## TL;DR

Reducing proteinuria early in Japanese patients with IgA nephropathy is linked to better long-term kidney outcomes, suggesting it can be a valid shortcut for drug trials.

## Contribution

Validates early proteinuria reduction as a surrogate endpoint for IgA nephropathy in Japanese patients using real-world data.

## Key findings

- Patients with ≥30% early proteinuria reduction had significantly lower risk of kidney failure.
- Annual eGFR decline was slower in the UPCR reduction group compared to the non-reduction group.
- Greater UPCR reductions were linearly associated with more favorable eGFR slopes.

## Abstract

Early reduction in proteinuria has been validated as a surrogate endpoint for IgA nephropathy (IgAN) in Western trials and is used for accelerated drug approval. However, its applicability to Japanese patients remains unclear. We aimed to evaluate the association between early proteinuria reduction and long-term renal outcomes in Japanese patients with IgAN.

This retrospective observational study used data from J-CKD-DB-Ex, a real-world database of CKD in Japan. Adult participants with IgAN, baseline urine protein/creatinine ratio (UPCR) ≥ 0.5 g/gCr, and eGFR ≥ 30 mL/min/1.73 m2 were included. The exposure was a ≥ 30% UPCR reduction at 9–12 months after the index date (UPCR reduction group), vs participants without such reduction (non-UPCR reduction group). The primary endpoint was a composite of 40% decline in eGFR from baseline or onset of CKD stage G5. Cox proportional hazards and linear mixed-effects models evaluated the association between UPCR reduction, renal events, and eGFR slope.

Among 385 participants (mean observation period 2,040 days), 245 achieved ≥ 30% reductions in UPCR. The UPCR reduction group showed significantly lower cumulative incidence of renal composite events than the non-UPCR reduction group. Annual eGFR decline was slower in the UPCR reduction group than that in the non-UPCR group (−1.9 vs −3.4 mL/min/1.73 m2/year). Greater UPCR reductions were linearly associated with more favorable eGFR slope.

Early proteinuria reduction is associated with decreased risk of renal failure and attenuated eGFR decline in Japanese patients with IgAN, supporting its validity as a surrogate endpoint for renal prognosis.

The online version contains supplementary material available at 10.1007/s10157-025-02788-4.