Association between remission of hematuria and subsequent renal outcomes in biopsy-proven IgA nephropathy

Hematuria is a cardinal clinical feature of IgA nephropathy (IgAN). Macroscopic hematuria may occur during an infection, but most patients have microscopic hematuria that may remit after treatment; others have persistent microscopic hematuria during long-term follow-up. Whether hematuria persistence is associated with worse kidney outcomes is poorly understood. We evaluated whether remission of hematuria at 6 months after treatment initiation is associated with subsequent renal outcomes.

We conducted a single-center retrospective cohort of biopsy-proven IgAN at Hiroshima University Hospital from April 2010 to March 2024, with a maximum follow-up of 3 years after treatment initiation. We excluded patients who died, progressed to end-stage kidney disease, those with a ≥50% decline in estimated glomerular filtration rate within 6 months, those with secondary IgAN, and those lost to follow-up. We recorded baseline demographics, comorbidities, laboratory and pathological findings, and treatment strategies (tonsillectomy, corticosteroids, other immunosuppressants, renin–angiotensin system inhibitors). The primary outcome was a composite of end-stage kidney disease or ≥30% decline in the estimated glomerular filtration rate from baseline. Hematuria at 6 months was analyzed as ordered categories (remission: <5 red blood cells (RBC)/high-power field (HPF), persistent moderate: 5–29 RBC/HPF, and persistent severe: ≥30 RBC/HPF) and as a continuous exposure using restricted cubic splines. Primary models were Cox proportional hazards with adjustment for baseline covariates measured at biopsy. For analyses of treatment interventions, we focused on tonsillectomy and corticosteroid therapy by 6 months; we used propensity scores based on baseline covariates to conduct overlap-weighted Cox models and 1:1 nearest-neighbor propensity-score matching in sensitivity analyses.

In total, 266 patients were analyzed, with median age 43 years (interquartile range, 30–55); 136 (48.2%) were male, and 144 (54.1%) underwent tonsillectomy, most of whom also received corticosteroid therapy. During median 2.9-year follow-up, 33 (12.4%) patients reached the composite outcome. Remission of hematuria was achieved in 116 patients (43.6%). Kaplan–Meier curves showed progressively worse renal outcomes with increasing hematuria category at 6 months of treatment. Compared with remission (<5 RBC/HPF), persistent severe hematuria (≥30 RBC/HPF) was independently associated with greater risk of the composite outcome (hazard ratio 2.79, 95% confidence interval 1.44–5.40, P<0.01). Standardized 3-year risk estimates remained higher in the ≥30 RBC/HPF group after adjustment for baseline covariates. Tonsillectomy and corticosteroid therapy were associated with lower hazards in overlap-weighted model, although the estimates were imprecise. Similar results were obtained in matching analyses.

Failure to achieve remission of hematuria by 6 months, particularly persistent severe hematuria (≥30 RBC/HPF) was associated with worse subsequent kidney outcomes in IgAN. Monitoring hematuria at 6 months as an intermediate marker and targeting remission may aid clinical management.