Real-World Renal Effects of Dapagliflozin in Bulgarian Patients with Chronic Kidney Disease of Predominantly Glomerular Origin: A Two-Year Comparative Cohort Study with Historical Controls

Background/Objectives: Sodium–glucose cotransporter 2 (SGLT2) inhibitors are established in the treatment of chronic kidney disease (CKD), but evidence in CKD caused by glomerular disease is limited, and patients on intensified immunosuppression have been excluded from the randomised trials. We examined the effect of dapagliflozin on proteinuria and kidney function over two years in such a population. Methods: In this single-centre retrospective cohort study, we compared 147 patients treated with dapagliflozin 10 mg daily between 2021 and 2025 with 170 historical controls followed between 2014 and 2021; most had biopsy-proven glomerular diseases. Proteinuria and estimated glomerular filtration rate (eGFR) were assessed at months 0, 12 and 24, and comparisons used analysis of covariance adjusted for baseline. Subgroups on intensified immunosuppression at entry were prespecified. Results: Proteinuria fell by 51.9% under dapagliflozin and by 22.2% in the historical cohort; the adjusted geometric mean ratio (GMR) was 0.684 (95% CI 0.534–0.878; p = 0.003). During the second year, eGFR declined more slowly with dapagliflozin (a difference of 4.61 mL/min/1.73 m2 per year; 95% CI 1.82–7.41; p = 0.001), although eGFR at month 24 did not differ significantly after adjustment for baseline (p = 0.15). An eGFR below 15 mL/min/1.73 m2 was reached by 0.7% of treated patients and by 11.8% of controls. Among patients on intensified immunosuppression, proteinuria fell by 67.5% when dapagliflozin was added, compared with 4.6% on the same treatment alone (adjusted GMR 0.371; 95% CI 0.234–0.586; p < 0.001). Conclusions: Dapagliflozin was associated with a progressive antiproteinuric effect, most marked in patients on intensified immunosuppression, and with a slower decline in kidney function during the second year. Because this study was observational, the true effects are likely to be smaller than those observed.