Histopathological predictors of renal outcomes in idiopathic membranous nephropathy with a focus on global sclerotic glomeruli ratio

Abstract

Abstract Idiopathic membranous nephropathy (MN) shows variable renal outcomes, and reliable histologic markers for risk stratification are limited. The global sclerotic glomeruli ratio (GSGR) may reflect chronic kidney damage and help predict progression, but its prognostic value and optimal threshold remain unclear. We retrospectively analyzed 322 patients with biopsy-proven idiopathic MN from the Turkish Society of Nephrology-Glomerular Diseases Study Group registry, excluding those with an estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m² at diagnosis or insufficient data. GSGR was calculated as the percentage of globally sclerotic glomeruli among total glomeruli. Histopathological parameters, including exudative glomerular changes, tubular atrophy/interstitial fibrosis (TA/IF), and vascular alterations, were semi-quantitatively graded according to the Renal Pathology Atlas (Fogo, 2022). Specifically, TA/IF was graded as: Grade 0 (< 5%), Grade 1 (5–25%), Grade 2 26–50%, and Grade 3 (> 50%) of cortical area involvement. Exudative changes were defined as intracapillary leukocyte accumulation and hyaline deposits in ≥ 25% of non-sclerotic glomeruli. The primary composite outcome was ≥ 50% eGFR decline from baseline, progression to eGFR < 15 mL/min/1.73 m², dialysis initiation, or kidney transplantation. Median follow-up was 60 months (IQR 48–72). Thirty patients (9.3%) reached the composite outcome. Receiver operating characteristic analysis identified a GSGR threshold of 15.7% (AUC 0.956; sensitivity 93.3%; specificity 82.7%). Patients with GSGR ≥ 15.7% had significantly higher event rates (35.1% vs. 1.2%; p  < 0.001). In multivariate analysis, high GSGR, exudative changes, and response to immunosuppressive therapy independently predicted adverse outcomes. These associations remained significant across treatment subgroups. Sensitivity analyses confirmed these associations across multiple model specifications. Anti-PLA2R positivity correlated with higher baseline proteinuria but not independently with renal outcomes. A GSGR ≥ 15.7% is a strong, independent predictor of renal progression in idiopathic MN. Incorporating GSGR and exudative changes into risk stratification may improve prognostic assessment and therapeutic decision-making.