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Introduction Hematuria is a hallmark feature of IgA nephropathy; however, its long-term impact on kidney outcomes remains incompletely characterized due to time-dependent confounding and lack of a standardized cutoff. This study evaluated the longitudinal association between hematuria and kidney disease progression. Methods We included 1,771 participants with biopsy-proven IgA nephropathy. Hematuria was categorized into four groups: <10, 10 to <20, 20 to <100, and ≥100 RBC/μL. The primary outcome was a composite kidney outcome (40% eGFR decline or kidney failure). Conventional Cox proportional hazards models were used to assess baseline hematuria, while marginal structural models (MSMs) were employed to evaluate time-updated hematuria, accounting for time-dependent confounders and fluctuations in clinical parameters. Results 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 (HR = 1.53; 95% CI, 1.14–2.06). The adverse impact was particularly pronounced in subgroups with a baseline eGFR <60 mL/min/1.73m 2 and those with baseline proteinuria ≥0.5 g/day. 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/1.73m 2 . Conclusions 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.
Tang et al. (Tue,) studied this question.