Comparative Analysis of Clinical and Pathological Traits in IgA Nephropathy Patients with Nephrotic Syndrome or Nephrotic Range Proteinuria.

INTRODUCTION: IgA nephropathy (IgAN) with nephrotic-range proteinuria (NRP) comprises two distinct presentations - with and without hypoalbuminemia, and comparative outcome data are limited, particularly for patients with preserved serum albumin. METHODS: From a multicenter cohort of patients with IgAN and NRP, 127 patients were divided into a nephrotic syndrome (NS) group (NRP with hypoalbuminemia) and an NRP with normal serum albumin (NRP-NA) group. We compared baseline features, one-year outcomes, and progression to a composite endpoint of a ≥ 30% decline in estimated glomerular filtration rate (eGFR) or progression to end-stage kidney disease and evaluated predictors of the composite endpoint. Immunosuppressive exposure was ascertained, and proteinuria response was classified as complete or partial remission. RESULTS: The NS group showed higher levels of C-reactive protein, lipids, and proteinuria and exhibited more pronounced diffuse foot process effacement than the NRP-NA group. After one year, the NS group demonstrated greater eGFR recovery and proteinuria reduction than the NRP-NA group. Overall remission rates were similar (75.61% vs 81.71%), but complete remission was three times more frequent in the NS group (29.27% vs 9.76%, P = 0.009) whereas the NRP-NA group more often remained in partial remission (46.34% vs 71.95%, P = 0.009). Composite endpoint-free survival was lower in the NS group (P = 0.010), but this difference did not persist after adjustment for baseline eGFR (hazard ratio [HR], 1.586; 95% confidence interval [CI], 0.883-2.849; P = 0.123). In multivariable analysis, baseline eGFR was the dominant predictor of the composite outcome (HR per mL/min/1.73m2, 0.978; 95% CI, 0.967-0.989; P < 0.001), whereas renin-angiotensin system inhibition was independently associated with a lower risk of kidney events (HR, 0.357; 95% CI, 0.146-0.874; P = 0.024). CONCLUSION: IgAN patients with NS and those with NRP-NA showed distinct patterns of proteinuria response, and the apparent difference in long-term kidney outcome did not persist after adjustment for baseline kidney function. Renin-angiotensin system inhibition was independently associated with a lower risk of kidney disease progression.