Risk of kidney failure across proteinuria levels among patients with immunoglobulin A nephropathy and stable estimated glomerular filtration rate

Abstract Introduction Proteinuria is an established prognostic marker in immunoglobulin A nephropathy (IgAN). Its relevance among patients with stable estimated glomerular filtration rate (eGFR) is less well characterized. This study evaluated patients with stable eGFR to assess if cumulative time-averaged proteinuria (TA-P) is associated with subsequent kidney failure. Methods This retrospective cohort study used linked US claims from Komodo Research Data and electronic medical records (EMR) data from Norstella (2016–2026). Eligible patients were adults aged ≥ 18 years with IgAN identified through diagnosis codes or clinical notes, from claims or EMR. eGFR stability was defined as an annualized slope corresponding to a decline of < 1 mL/min/1.73 m² assessed over 24 (± 6) months. Multivariable Cox proportional hazards models estimated associations between TA-P thresholds and kidney failure, adjusting for demographics, baseline kidney function, comorbidities, hematuria, and treatment use. Results One thousand, two hundred twenty-three patients met the inclusion criteria including having stable eGFR for 2 years. Despite having stable eGFR, patients with TA- P ≥ 0.5 g/day had 1.55 times the hazard of kidney failure compared with patients with TA- P < 0.5 g/day (HR, 1.55; 95% CI, 1.07–2.23; p = 0.019). A similar finding was demonstrated for patients with TA- P ≥ 0.3 g/day versus TA- P < 0.3 g/day (HR, 1.80; 95% CI, 1.21–2.67; p = 0.004). Consistent results were observed across sensitivity analyses including a 1-year stability period. Conclusions Among patients with IgAN and stable eGFR over a 24-month period, achieving the KDIGO-recommended proteinuria targets (< 0.5 g/day, preferably < 0.3 g/day) remains clinically important even when kidney function appears stable.