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

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.

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.

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).

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.