#3115 Effectiveness of SGLT2 inhibitors in patients with glomerulonephritis: a single center experience

Abstract Background and Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors have become widely used in recent years because of favorable outcomes on kidney function in people with diabetes mellitus and chronic kidney disease (CKD). The main effect of SGLT2 inhibitors is inhibiting sodium and glucose reabsorption, acting precisely in the early proximal tubule of the renal nephron. Although these drugs developed as glucose-lowering agents for their capability to induce glycosuria, cardiovascular outcome studies found that the reduction in kidney function was significantly delayed, and the incidence of severe decline in kidney function was reduced in patients taking SGLT2 inhibitors. Later on, these outcomes were confirmed by the results of the DAPA-CKD, EMPA-KIDNEY, and CREDENCE studies, which were specific outcome trials in patients with CKD. However, data about the use of SGLT2 inhibitors in patients with glomerulonephritis at routine clinical practice are still limited. The purpose of this study is to investigate the impact of SGLT2 inhibitors use in patients with glomerulonephritis. Method Patients diagnosed with biopsy-proven GN who continued their routine follow-up in Etlik City Hospital nephrology clinic were retrospectively examined. Patients with a steroid treatment history for GN were excluded from this study. We identified 29 patients who were treated with SGLT2 inhibitors for proteinuria. We analyzed the baseline characteristics, comorbidities, GN types, and laboratory parameters (baseline, sixth and twelfth months at the follow-up). Each patient was matched to the control with a similar baseline feature under conservative therapy (n = 29). Both patient groups were treated in line with the KDIGO glomerulonephritis guideline and were received RAAS blockers at the maximum tolerated dose. According to baseline levels, the reduction rate in proteinuria and eGFR of the sixth and twelfth months were calculated as percentages. The study was performed in accordance with the Declaration of Helsinki. The local ethical committee approved the study design. Results Our study involved 58 patients diagnosed with 32 (55%) IgA nephropathy, 16 (28%) with membranous nephropathy, and 10 (17%) with focal segmental glomerulosclerosis. In the treatment group, 23 (79%) patients used dapagliflozin, and 6 (21%) used empagliflozin as SGLT2 inhibitors. Baseline proteinuria levels at 1940 (1780-2700 mg/d) vs. 1890 (1670-2400 mg/d); p = 0.8, eGFRs 60 (44-82) vs. 64 (46-80) ml/min/1.73 m2; p = 0.8 and serum albumin levels (39.6 ± 0.3 vs. 39.1 ± 0.2; p = 0.4) were similar between both groups. The proteinuria reduction rate in the sixth month was 34% (27.3-40.5) for the treatment group and 12% (6.9-20.7) for the control group (0.0001). Besides, the reduction rate was still higher in the treatment group at the 12th month 50.5% (39-52.6) vs. 26.3% (17.2-35.4); p ≤ 0.0001. eGFR declining rate at 6th months and 12th months were lower in SGLT2 group than the control group 3.1% (0-6.2) vs. 8.6% (4.1-16.6); p = 0.004 and 0.8% (0-5) vs. 5.9% (3.3-15.2); 0.005, respectively (Table 1). Proteinuria levels at 6th months were 1170 (970-1890) mg/d and 1730 (1180-2100) mg/d for treatment and control group, respectively. At 12th months, median proteinuria level of SGLT2 group was 940 (840-1480) mg/d and control group was 1250 (1120- 2040) mg/d (Fig. 1). Conclusion In this study with a well-matched control group, we found that SGLT2 inhibitors demonstrate efficacy in mitigating the decline in estimated GFR and reducing albuminuria in patients with GN. However, randomized-controlled trials are still required specific to patients with GN.