#854 Real world experience with SGLT2 inhibitors in IgA nephropathy: a case-control study

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) determined a significant improvement in proteinuria and a reduction of the risk of chronic kidney disease progression in patients with IgA Nephropathy (IgAN). We sought to evaluate the impact of treatment with SGLT2i in a real-world cohort of patients with IgAN by comparison with a historical, matched cohort of patients without SGLT2i. Method From a retrospective cohort of 230 patients with IgAN, we identified 68 patients that underwent treatment with SGLT2i for at least 6 months. In addition, we selected 68 control patients with IgAN not treated with SGLT2i, matched for age and eGFR at the moment of biopsy and duration of follow-up. The primary composite endpoint was the occurrence of an eGFR decline by at least 50%, progression to ESRD or death, whichever came first. Results The two cohorts were balanced in terms of their baseline characteristics. The mean age, median eGFR and median proteinuria were 43.1 ± 11.9 years, 56 ml/min (IQR: 39.2–74) and 1.44 g/day (IQR:0.82–3.2), respectively, in those treated with SGLT2i and 42.2 ± 11.9 years, 54.5 ml/min (IQR: 38–74.5) and 1.5 g/day (IQR: 0.57–3.14), respectively, in those not treated with SGLT2i (P = 0.68, P = 0.68 and P = 0.51, respectively). There was a tendency for those not treated with SGLT2i to exhibit a higher prevalence of E1 (23.5% vs. 14.7%, P = 0.19) and C1 lesions (14.7% vs. 7.4%, P = 0.39), and a lower prevalence of S1 lesions (54.4% vs. 67.6%, P = 0.11), but did not reach statistical significance. In addition, those treated with SGLT2i had a higher use of mineralocorticoid receptor blockers (13.2 vs. 0%, P = 0.003) and a tendency for a lower use of immunosuppression (77.9% vs. 88.1%, P = 0.11). The median treatment duration with SGLT2i was 26.5 months (IQR: 11.2–36), while the median duration of follow-up was similar between the two study groups [37 months (18.3–81.7) vs. 38 months (IQR: 17–79.4), P = 0.91]. Patients not treated with SGLT2i reached the primary composite endpoint in a higher proportion compared to those treated with SGLT2i (41.2% vs. 11.8%, P < 0.001), the difference being driven mainly by ESRD occurrence (35.3% vs. 4.4%). In addition, the time to a primary composite endpoint event occurrence was prolonged, albeit not statistically significant, with the use of SGLT2i [83.5 months (IQR: 25.8–107.8) vs. 50.3 months (IQR: 18.7–87.2), P = 0.37]. When evaluating this combined cohort according to risk of disease progression, we identified, after multivariate Cox proportional hazards regression analysis, that baseline eGFR (HR, 0.96; 95%, 0.93–0.99), T2 score (HR, 5.54; 1.56–19.5) and C2 score (HR, 19.4; 2.05–183) were independent predictors of the primary composite endpoint. In addition, treatment with SGLT2i independently determined an 82% reduction in the risk of the primary composite endpoint (HR, 0.18; 95%, 0.06–0.5). Conclusion In a real-world cohort of patients with IgAN, treatment with SGLT2i led to a significant improvement in the risk of disease progression by comparison to a historical-matched group of IgAN patients not treated with SGLT2i.