Reduction of Proteinuria with the Use of SGLT2 Inhibitors Combined with ACE Inhibitors or ARBs and Immunosuppression in Patients with Primary or Secondary Glomerulopathies in Western Mexico

Background: The role of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in the management of glomerular diseases (GD) with proteinuria in clinical settings is not clear for all GDs. Current studies in Focal Segmental Glomerulosclerosis (FSGS) and IgA Nephropathy (IgAN) are approved, and Phase II studies in Lupus Nephritis (LN) are ongoing. The primary objective was the percentage reduction of 24-hour proteinuria from the start of SGLT2i until the 3,6,12 months follow-up. (All patients were using ACE inhibitors or ARBs and started immunosuppression (IS) in the case of LN). Methods: 50 patients with GD were included between January 2019-2025 in an observational, analytical, and prospective study. Multivariate logistic regression analysis was performed to identify factors associated with a reduction in proteinuria >30%, with significance at p<0.05. Results: 50 patients with a mean age of 35 [±12] years; 33 (66%) women, 6 (12%) with obesity, 30 (60%) with NL, 6 (12%) with FSGS, 4 (8%) with ANCA vasculitis, and 4 (8%) with IgAN. The mean proteinuria was 5,027 [±4,260] mg/day on day 1, the 86% of the patients had a reduction of ≥30% in proteinuria at 12 months, with 78% achieving a reduction of more than 50%. IgAN showed the greatest response to treatment, with 100% of patients achieving a ≥50% reduction and an increase of 16.8 ml/min in eGFR at 12 months. In patients with LN, 80% had a reduction in proteinuria of ≥30%, and 71% of cases had a ≥50% reduction with an increase in eGFR of 16.8 ml/min at 12 months. Factors associated with a reduction in proteinuria >30% included being female (OR 1.47, 95% CI 1.10-1.96, p<0.01) and IgAN (OR 3.06, 95% CI 1.07-8.76, p=0.04), while obesity was associated with a lower probability of a >30% reduction (OR 0.64, 95% CI 0.43-0.97, p=0.04). Adverse events in 8 patients (infections, none related to SGLT2 inhibitors, pneumonia, and catheter infection) Conclusion: In this study, SGLT2 inhibitors showed significant efficacy and safety in reducing proteinuria in various types of GN, especially in IgAN and LN. The reduction in proteinuria and improvement in eGFR was better than in another study (expecting a greater benefit after 6 months, primarily from the iSGLT2)