Persistent Hematuria and Kidney Disease Progression in IgA Nephropathy: A Cohort Study

Rationale & objective: Hematuria is the most typical presentation of immunoglobulin A nephropathy (IgAN); however, its role in disease progression is still controversial. This study aimed to evaluate the association of hematuria and progression of IgAN.

Study design: Retrospective cohort study.

Setting & participants: A cohort of 1,333 patients with IgAN treated at a Chinese referral hospital with a median follow-up of 45 months.

Predictors: Microhematuria was evaluated in fresh urine using a fully automated urine particle analyzer (automated method) and urine sediment examination by a skilled examiner (manual method). Hematuria was characterized as a time-varying attribute; namely, average hematuria level was calculated for every 6-month period for each patient during follow-up. Remission was defined as average red blood cell count ≤5/high-power field (manual method) or ≤28 red blood cells/μL (automated method) during the first 6 months of follow-up.

Outcomes: Composite event of 50% decline in estimated glomerular filtration rate or development of kidney failure.

Analytical approach: Multivariable cause-specific hazards models to analyze the relationship between hematuria and the composite kidney disease progression event.

Results: Time-varying hematuria during follow-up was an independent risk factor for the composite kidney disease progression event (HR, 1.46; 95% CI, 1.13-1.87; P = 0.003). Hematuria remission during the 6 months after diagnosis was associated with a significantly lower rate of the composite kidney disease progression event (HR, 0.41; 95% CI, 0.28-0.61; P < 0.001). A significant interaction was detected between remission of proteinuria and remission of hematuria during the first 6 months (P < 0.001). The association between remission of hematuria and kidney disease progression was detectable (HR, 0.46; 95% CI, 0.32-0.68) within the subpopulation with persistent proteinuria (protein excretion > 1.0 g/d during the first 6 months), but not among patients whose proteinuria had remitted (HR, 0.64; 95% CI, 0.31-1.29; P = 0.2). The 2 techniques for hematuria evaluation were strongly and significantly linearly correlated (r = 0.948; P < 0.001), and results using these 2 methods were consistent.

Limitations: A single-center retrospective study. Proportional hazards regression incorporating time-varying covariates may create time-varying confounding. The predictive value of reductions in hematuria was not directly evaluated.

Conclusions: Level of hematuria was independently associated with kidney disease progression, whereas hematuria remission was associated with improved kidney outcomes in IgAN among patients with persistent proteinuria. Additionally, to monitor IgAN progression, automated methods to evaluate hematuria hold promise as a replacement for manual evaluation of urinary sediment.