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

Abstract

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, 1-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 1 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/1.73 m2, 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.