Post-biopsy proteinuria as a universal prognostic marker across diverse clinical courses in IgA nephropathy

Background Although proteinuria is a key prognostic marker in immunoglobulin A nephropathy (IgAN), the optimal post-biopsy timing for its assessment remains uncertain, particularly given variability in treatment type and timing. Using longitudinal data from the Japan IgA Nephropathy Prospective Cohort Study (J-IGACS), we sought to identify the post-biopsy time point at which proteinuria most reliably predicts kidney outcomes. Methods Proteinuria was assessed at baseline and at 6, 12, 18, and 24 months after biopsy. The primary outcome was defined as a ≥ 50% increase in serum creatinine or initiation of kidney replacement therapy in adults (≥ 20 years) and as a ≥ 25% decline in eGFR or initiation of kidney replacement therapy in patients aged < 20 years. Model performance was compared using the corrected Akaike Information Criterion. Results Among 588 patients (median age 38 years; mean eGFR 76.5 mL/min/1.73 m 2 ; median proteinuria 0.64 g/day), 43 (7.3%) reached the primary outcome during a median 78-month follow-up. Proteinuria at all time points was independently associated with kidney outcomes, with the 18-month measurement providing the best model fit. A threshold of 0.44 g/day (or g/gCr) yielded 79% sensitivity and 81% specificity, and patients with proteinuria ≥ 0.44 g/day at 18 months had significantly worse outcomes. Cox regression confirmed a robust association for 18-month proteinuria, irrespective of treatment type or timing. Conclusions Proteinuria measured 18 months post-biopsy showed the strongest association with long-term kidney outcomes in IgAN, supporting its use as a universal treatment target across heterogeneous post-biopsy clinical courses.