Prognostic Value of the Ratio of Globally Sclerotic Glomeruli in Patients With Idiopathic IgA Nephropathy

Abstract

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. We assessed whether the Ratio of Globally Sclerotic Glomeruli (RoGSG) on diagnostic biopsy predicts subsequent kidney outcomes in a nationwide, multi-center registry. Among 326 adults with idiopathic IgAN (mean age 39.1 +/- 12.8 years; 60.1% male), 43 patients (13.2%) met a 5 year composite outcome defined as any of: doubling of serum creatinine or >= 50% decline in eGFR from baseline, eGFR < 15 mL/min/1.73 m(2), or initiation of kidney replacement therapy. Receiver operating characteristic analysis identified a RoGSG cutoff of 28.86% for predicting the composite outcome (AUC 0.917, 95% CI 0.885-0.949; sensitivity 93.0%; specificity 84.5%). Using this threshold, 47.6% of patients with RoGSG >= 28.86% versus 1.2% with RoGSG < 28.86% reached the composite outcome. In multivariable models adjusted for clinical and pathologic covariates, high RoGSG, grade 2 tubular atrophy/interstitial fibrosis, and non-response to initial immunosuppression were independent predictors of adverse outcomes. The prognostic association of RoGSG persisted in key subgroups, including those with nephrotic syndrome and those with initial treatment response. These findings support RoGSG as a readily available histopathologic marker that may improve risk stratification in IgAN; however, prospective studies and external validation in independent cohorts are required before any clinical adoption.