Early risk stratification in lupus nephritis based on established prognostic factors: association with outcomes under triple therapy

Abstract Background To apply the 2025 EULAR prognostic factors to identify subgroups of patients with lupus nephritis (LN) in which triple therapy was associated with higher complete renal response (CR) rates. Methods We conducted a medical record review of patients with biopsy-proven class III, IV, or V LN who were treated at our hospital between 2000 and 2024. Multivariate logistic regression was used to identify EULAR 2025 prognostic factors independently associated with CR. Patients were stratified according to major prognostic factors and the cumulative burden of additional factors. Cumulative CR rates were compared, and Cox proportional hazards models were applied to evaluate the association between risk stratification and CR. Results Among the 170 patients included in this study, nephrotic-range proteinuria and a history of previous LN flare were negatively associated with CR (odds ratio [OR] 0.25, 95% confidence interval [CI] 0.11–0.55, p < 0.01 and OR 0.29, 95% CI 0.12–0.65, p < 0.01, respectively). Using a stepwise risk stratification approach incorporating these factors and the cumulative number of remaining prognostic factors, patients were classified into low-, moderate-, and high-risk groups, showing a clear gradient in CR rates (94.0% vs. 71.8% vs. 40.9%, respectively, p < 0.01). Using the high-risk group as the reference, the likelihood of achieving CR was substantially higher in the low- and moderate-risk groups (hazard ratio [HR] 22.8, 95% CI 8.27–81.24, p < 0.01 and HR 3.7, 95% CI 1.53–9.52, p = 0.01). In the high-risk group, triple therapy remained independently associated with CR (adjusted HR 3.13, 95% CI 1.17–8.73, p = 0.02). Conclusions These findings suggest that baseline risk stratification identified subgroups in which triple therapy was associated with higher CR rates. Prospective validation in independent cohorts is required before this approach can inform treatment selection.