Evaluation of the effects of SGLT-2 inhibitor use on renal function and proteinuria in stage-3 and stage-4 chronic kidney disease patients

ABSTRACT İntroduction and aim: Chronic kidney disease (CKD) is an important public health problem due to its increasing prevalence and high cardiovascular risk, with proteinuria and decline in glomerular filtration rate (GFR) being key determinants of disease progression. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have recently gained attention for their renoprotective effects independent of glycemic control. However, real-world data on their effectiveness, particularly in patients with stage 3–4 CKD, remain limited. This study aimed to retrospectively evaluate the effects of SGLT-2 inhibitor use on GFR changes, proteinuria levels, biochemical parameters, and progression to end-stage kidney disease (ESKD) in patients with stage 3–4 CKD. Methods: This retrospective study included patients with stage 3–4 CKD who were followed at the outpatient clinics and inpatient services of Dicle University Faculty of Medicine, Department of Internal Medicine between February 1, 2020 and May 1, 2025. Eligible patients had a baseline GFR between 20–60 mL/min/1.73 m², classified according to KDIGO criteria. Patients were grouped as SGLT-2 inhibitor users (n=55) and non-users (control group, n=69). Laboratory data at baseline, 6 months, and 12 months—including hemogram, biochemical parameters, lipid profile, fasting glucose, HbA1c, spot urine protein and creatinine, and blood gas analysis—were extracted from electronic records. GFR was calculated using the CKD-EPI formula, and proteinuria was quantified using spot urine protein/creatinine ratio. Incomplete or inconsistent records were excluded. Data were analyzed using appropriate statistical methods, including Student's t-test, Mann-Whitney U test, and repeated-measures analyses, with p<0.05 considered significant. Results: GFR decline at 6 and 12 months was significantly slower in the SGLT-2 inhibitor group compared with controls (p<0.05 and p<0.01, respectively). The spot urine protein/creatinine ratio showed a significant reduction in the treatment group, whereas the control group demonstrated a progressive increase (p<0.01 for both intervals). The annual rise in serum creatinine was significantly lower in SGLT-2 inhibitor users, with the 12-month difference reaching statistical significance (p<0.05). Favorable changes were also observed in urea, hemoglobin, and other biochemical parameters (p<0.05). Progression to ESKD occurred in 5.5% of the SGLT-2 inhibitor group and 20.3% of the control group, demonstrating a significant difference (p<0.05). These findings indicate that SGLT-2 inhibitors slow GFR decline, reduce proteinuria, and lower the risk of progression to ESKD in stage 3–4 CKD patients. Conclusion: SGLT-2 inhibitor use provides meaningful renoprotective benefits in patients with stage 3–4 CKD, reflected by slower GFR decline, significant reductions in proteinuria, and a lower rate of progression to ESKD. These real-world data support the role of SGLT-2 inhibitors as an effective therapeutic option in the management of moderate to advanced CKD. Keywords: Chronic Kidney Disease, SGLT-2 Inhibitors, Glomerular Filtration Rate, Proteinuria, Renal Function, Stage 3–4 CKD, End-Stage Kidney Disease.