Association between hematuria remission at 6 months and subsequent kidney outcomes in IgA nephropathy

BACKGROUND: While proteinuria is a well-established surrogate marker in IgA nephropathy (IgAN), the independent prognostic value of early hematuria remission remains unclear. We hypothesized that treatment response at 6 months, particularly hematuria status, is associated with subsequent kidney outcomes. METHODS: We conducted a single-center retrospective cohort study of biopsy-proven IgAN at Hiroshima University Hospital between April 2010 and March 2024. A 6-month landmark analysis was used to minimize immortal time bias, including patients who were event-free at 6 months, with follow-up starting at that time. Urinary red blood cell (uRBC) count at 6 months was used to classify patients into remission (<5 RBC/high-power field [HPF]), persistent moderate (5-29 RBC/HPF), and persistent severe (≥30 RBC/HPF). The primary outcome was a composite of end-stage kidney disease or a ≥30% decline in the estimated glomerular filtration rate. Multivariable Cox models, Kaplan-Meier analyses, and restricted cubic spline models were performed. RESULTS: A total of 286 patients were analyzed (median age 43 years; 48.2% male). During a median follow-up of 3.1 years, 38 patients (13.3%) reached the composite outcome. Compared with remission, persistent severe hematuria was associated with higher risk of the outcome (hazard ratio 2.97, 95% confidence interval 1.33-6.67, P = 0.01). Restricted cubic spline analyses demonstrated a graded association between higher uRBC count and worse kidney outcomes. CONCLUSION: Persistent severe hematuria at 6 months was independently associated with worse kidney outcomes. Monitoring hematuria at 6 months may provide a clinically useful marker for risk stratification in patients with IgAN.