Time-Updated Hematuria and Kidney Disease Progression in IgAN

Hematuria is a hallmark feature of IgA nephropathy (IgAN); however, its long-term impact on kidney outcomes remains incompletely characterized because of time-dependent confounding and lack of a standardized cutoff. This study evaluated the longitudinal association between hematuria and kidney disease progression.

We included 1771 participants with biopsy-proven IgAN. Hematuria was categorized into the following 4 groups: < 10, 10 to < 20, 20 to < 100, and ≥ 100 red blood cells (RBC)/μl. The primary outcome was a composite kidney outcome (40% estimated glomerular filtration rate [eGFR] decline or kidney failure). Conventional Cox proportional hazards models were used to assess baseline hematuria, whereas marginal structural models (MSMs) were employed to evaluate time-updated hematuria, accounting for time-dependent confounders and fluctuations in clinical parameters.

During a median follow-up of 48 months, the primary outcome occurred in 487 (27.5%) participants. In the fully adjusted baseline Cox model, baseline hematuria was not significantly associated with the primary outcome. In contrast, MSMs revealed that time-updated hematuria ≥ 100 RBC/μl was significantly associated with an increased risk of progression (hazard ratio [HR]: 1.53; 95% confidence interval [CI]: 1.14-2.06). The adverse impact was particularly pronounced in subgroups with a baseline eGFR < 60 ml/min per 1.73 m² and those with baseline proteinuria ≥ 0.5 g/d. Even moderate time-updated hematuria (20 to < 100 RBC/μl) was correlated with a substantially elevated risk (HR: 1.89; 95% CI: 1.33-2.72) in the subgroup with eGFR <60 ml/min per 1.73 m².

Our findings suggest that persistent hematuria ≥ 100 RBC/μl may serve as a valuable risk stratification standard, particularly given the significantly magnified risk in patients with pre-existing renal impairment or uncontrolled proteinuria.