#2673 Efficacy and safety of SGLT2 inhibitors in kidney transplant recipients with proteinuria, irrespective of diabetes status

Abstract Background and Aims Kidney transplantation is the most effective treatment for end-stage renal disease (ESRD). Previous studies have shown that post-transplant proteinuria is strongly associated with reduced long-term survival and graft function loss. Although SGLT-2 inhibitors have demonstrated efficacy in CKD, their role in KTRs, particularly those without diabetes, remains underexplored due to the complexity of post-transplant physiology and immunosuppressive therapies, which may alter drug efficacy and safety profiles. This study aimed to assess the efficacy and safety of dapagliflozin in proteinuric KTRs, irrespective of diabetes status. Method This prospective, real-world study enrolled 103 KTRs treated with dapagliflozin (ChiCTR2400087630). Mixed-effects repeated-measures models were used to assess changes in urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) over 12 months, with subgroup analysis based on diabetes status to assess the efficacy of proteinuria reduction. Secondary efficacy outcomes included changes in routine blood and urine biomarkers, and safety outcomes were also evaluated. Results Significant reductions in UACR were observed at all post-baseline time points (P < 0.001, Fig. 1), indicating a decrease in proteinuria over time. Although eGFR showed a slight decline at month 12 (from 63.43 ± 18.58 mL/min/1.73 m² at baseline to 61.28 ± 19.44 mL/min/1.73 m²), this change was not statistically significant (P > 0.05, Fig. 2). Regardless of diabetes status, dapagliflozin was similarly effective in reducing proteinuria among KTRs, with no significant differences observed between the two groups (P > 0.05, Fig. 3). Additionally, there were notable improvements from baseline in red blood cell count (P = 0.01), hemoglobin (P = 0.029), fasting blood glucose (P < 0.001), serum magnesium (P < 0.001), and serum phosphorus (P = 0.007). The use of dapagliflozin did not significantly affect the stability of immunosuppressive drug concentrations, which remained within the therapeutic range throughout the study period. A total of 15 patients (14.6%) reported adverse events. The most common adverse event was urinary tract infection (7.8%), followed by kidney-related adverse events (4.9%). No serious adverse events or deaths were reported during the study. Conclusion Dapagliflozin significantly reduced proteinuria in kidney transplant recipients, irrespective of diabetes status, and helped correct hypophosphatemia and hypomagnesemia. The drug demonstrated a favorable safety profile, with no serious adverse events and no significant impact on eGFR or immunosuppressive drug concentrations. These findings provide evidence for the anti-proteinuric efficacy and safety of short-term dapagliflozin in KTRs.