THE PERCENTAGE OF GLOBALLY SCLEROTIC GLOMERULI IN KIDNEY BIOPSY AS A PREDICTIVE FACTOR OF CHRONIC KIDNEY DISEASE PROGRESSION IN IGA NEPHROPATHY

Introduction: IgA Nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, marked by mesangial IgA deposition. The Oxford Classification (MEST-C score) is the standard histological evaluation, and includes 5 prognostic parameters. However, the percentage of globally sclerotic glomeruli (%GSG), an easily identifiable histological parameter, is emerging as an additional potential marker of disease severity. Objective: To investigate the value of %GSG as a predictor of disease progression in IgAN. Methods: Data from 1248 IgAN patients who underwent kidney biopsy between 2011 and 2023 were collected and analyzed, with histological assessment based on the MEST-C score. Patients were categorized into three groups according to their total MEST-C score using the O-grade system (I: 0–1, II: 2–4, III: 5–7 points). Multiple imputation via the multivariate imputation by chained equations (MICE) method was performed after dataset pattern evaluation. The primary outcomes were "glomerular filtration rate (GFR) ≤ 30 mL/min" and "O-grade III". Area under the ROC curve (AUC) analysis was performed. Multivariate logistic regression models were constructed and included predictors with P< 0.100 from univariate analysis. Results: 1248 patients were included; median age was 41.0 (32.1-51.0) years and median GFR was 50.6 (35.8-66.1) mL/min. 723 (57,9%) patients were male, 684 (54.8%) presented primary hypertension, and 1107 (88.7%) exhibited proteinuria > 1g/24h. The %GSG was 22.2 (8.3-44.4), with 497 (39.8%) exhibiting > 30% of GSG. GFR ≤ 30 mL/min was observed in 235 (18.8%) individuals, with 101 (8.1%) classifying as O-grade III. In all multivariate models, GSG > 30% presented the strongest association with markers of disease severity. A GSG > 30% independently associated with O-grade III (OR: 3.314, 95% CI: 2.132-5.150, P< 0.001), and with GFR ≤ 30 mL/min (OR: 3.223, 95% CI: 2.283-4.551, P< 0.001). Finally, at AUC analysis comprising the MEST-C predictors and the %GSG for the outcome “GFR ≤ 30 mL/min”, the association was greater for the %GSG (AUC: 0.760, 95% CI: 0.723-0.796, P< 0.001), and for the interstitial fibrosis/tubular atrophy (Oxford-T) (AUC: 0.778, 95% CI: 0.742-0.815, P< 0.001) parameters. Conclusion: The percentage of globally sclerotic glomeruli has proven to be an important marker of severity, outperforming most MEST-C predictors, except for Oxford-T.