Persistent microhematuria and risk of long-term kidney failure in adult patients with immunoglobulin A nephropathy (IgAN) in the United States

Abstract Background Persistent microhematuria is associated with disease progression in immunoglobulin A nephropathy (IgAN), but most of the studies that established the association were conducted outside of the United States (US). This real-world study evaluated the association between time-averaged hematuria (TA-H) and risk of kidney failure in a large US cohort. Methods This retrospective cohort study used linked administrative claims (Komodo Research Data) and Norstella electronic medical records (January 2016–January 2026). Adults (≥ 18 years) with IgAN and ≥ 2 hematuria measurements were included. Hematuria laboratory values, reported in red blood cells per high power field (RBC/HPF) or RBC/uL were converted to RBC/HPF. TA-H was assessed longitudinally and < 5 RBC/HPF was considered as hematuria resolution. A Cox proportional hazards model was used to evaluate the association between TA-H and kidney failure, defined as stage 5 chronic kidney disease, dialysis, kidney transplantation, or sustained estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2. Results Overall, 576 patients with IgAN were included (mean age 48.0 years; 53.6% male). Patients with persistent microhematuria (TA-H ≥ 5 RBC/HPF) were at increased risk of kidney failure versus those with hematuria resolution (TA-H < 5 RBC/HPF) (hazard ratio [HR] 1.56, 95% CI 1.02–2.37, p = 0.040) after controlling for proteinuria and eGFR. Conclusions Persistent microhematuria was associated with increased risk of kidney failure in patients with IgAN in the US, even after controlling for proteinuria and eGFR. These findings reinforce the clinical relevance of longitudinal hematuria assessment and its independent role in risk stratification and disease monitoring.