Prognostic Value of Baseline and Early Proteinuria Changes in IgA Nephropathy: A US Cohort Study
Published on June 8, 2026
Abstract
Introduction: Proteinuria is a key marker in IgA nephropathy (IgAN). However, long-term thresholds and significance of early changes in proteinuria remains unclear in US populations. Methods: Retrospective cohort study of 745 adult patients with IgA nephropathy from the TriNetX US network (2015–2023). The baseline Time-average proteinuria (TAP) were calculated and categorized as <500, 500–1,000, 1,000–2,000, and >2,000 mg/g. Starting 1 year post diagnosis, the composite kidney failure outcome (sustained eGFR ≤15 mL/min/1.73 m2, sustained >40% eGFR decline, initiation of dialysis, or all-cause mortality) was evaluated. Associations with baseline TAP and changes in TAP at first-year were evaluated using Kaplan-Meier analysis and multivariable Cox proportional hazard models. Results: Out of 745 patients (mean age 43.5 [±16] years, 58% male, 68% White), a composite outcome occurred in 175 (23.5%) of patients over a median follow-up of 5.4 years (IQR: 3.2–7.2). Survival analysis showed 13.8% of patients with TAP <500 mg/g remained at risk of kidney failure by 8 years. Compared to TAP <500 mg/g, adjusted hazard ratios were significantly higher for TAP 1,000–2,000 mg/g (aHR 2.84; 95% CI: 1.66–4.85) and TAP >2,000 mg/g (aHR 5.68; 95% CI: 3.45–9.36); whereas TAP 500–1,000 mg/g was not significant after adjustment (aHR 1.69; 95% CI: 0.96–2.97). Higher baseline eGFR and white race were associated with better outcomes. Among 389 patients with follow up TAP data at the first-year observation period, each one-category reduction in TAP was associated with ∼40% lower risk of composite outcome, and ≥30% and ≥50% proteinuria reductions were associated with 62% and 66% lower risk of composite outcome, respectively. Conclusions: In US adults with IgA nephropathy, baseline proteinuria exceeding 1,000 mg/g identifies a high-risk group. Early proteinuria reductions – either by category (TAP) or percentage (≥30–50%) – strongly predict improved outcomes. This study supports use of proteinuria as a modifiable, treat-to-target surrogate for prognosis and treatment monitoring.