Application of a Prognostic Prediction Model in IgAN in the Brazilian Population

Background: IgA nephropathy (IgAN) is the most common primary glomerular disease worldwide and a leading cause of chronic kidney disease (CKD). A major challenge in monitoring IgAN is its highly heterogeneous risk of progression, with 10-year progression to end-stage CKD ranging from 5% to 60%. Although risk stratification is recommended to guide immunosuppressive therapy, no tool was previously available to accurately predict CKD progression. To address this, an international IgAN-specific risk calculator was developed and validated. This study aimed to apply this tool to define renal prognosis in Brazilian patients with IgAN, identifying a cutoff associated with higher risk for adverse renal outcomes. Methods: This observational, retrospective, single-center study included 131 adult patients with biopsy-proven IgAN, followed at the glomerulonephritis outpatient clinic at UNIFESP/EPM between 2005 and 2015, with at least 5 years of follow-up. The international IgAN risk calculator was applied to each patient. The primary composite outcome was end-stage CKD (eGFR <15 ml/min, initiation of renal replacement therapy, or kidney transplantation) and/or a 50% decline in eGFR within 60 months post-biopsy. Results: Among 131 patients, 57.3% were male, mean age 46.5 years, mean follow-up 133.6 months; 61.8% were white. Mean eGFR at biopsy was 64.9 ± 21.3 ml/min; proteinuria was 2.53 ± 1.84 g/day. Outcomes occurred in 29.8% (n=39). Higher calculated risk correlated with greater prevalence of outcomes. A cutoff point of 22.78% optimally differentiated low/moderate from high/very high risk for adverse renal outcomes. The risk of a 50% eGFR decline was 49.2 times higher when the calculator result exceeded 27.78% (OR=49.2, 95% CI: 15.9–152.6). Renal survival was significantly better in patients with proteinuria <1 g/day (p=0.001), and dialysis-free survival was higher among those with eGFR >60 ml/min (p=0.028). Conclusion: Application of the international IgAN risk calculator effectively stratified Brazilian patients, independent of race. A robust cutoff point was identified to distinguish low from high-risk individuals for progression to end-stage CKD.