Effects of dapagliflozin on proteinuria, glycemic control, and treatment burden in diabetic kidney transplant recipients: a matched cohort study.

aimsDiabetes mellitus and persistent proteinuria are major determinants of cardiovascular morbidity, graft dysfunction, and mortality after kidney transplantation. Although sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated substantial cardiorenal benefits in chronic kidney disease, data regarding their use in kidney transplant recipients remain limited. This study aimed to evaluate the clinical effects of dapagliflozin on proteinuria, graft function, glycemic measures, treatment burden, and observed safety events in diabetic kidney transplant recipients.

methodsWe conducted an exploratory retrospective 1:1 clinically matched cohort study of diabetic kidney transplant recipients followed between 2010 and 2022. Among 282 transplant recipients, 68 had diabetes mellitus. Eighteen patients initiated dapagliflozin 10 mg/day and were included in the all-treated tolerability cohort; three discontinued treatment before completing 3 months because of patient preference unrelated to documented adverse events, leaving 15 recipients who received dapagliflozin for at least 12 months in the efficacy cohort. Fifteen diabetic kidney transplant recipients not receiving SGLT2 inhibitor therapy were selected as 1:1 clinically matched comparable controls according to prespecified matching criteria. Primary outcomes were changes in proteinuria and eGFR. Secondary outcomes included HbA1c, fasting plasma glucose, insulin requirements, antihypertensive medication burden, and observed safety events.

resultsThirty diabetic kidney transplant recipients were included in the 12-month efficacy analysis (15 dapagliflozin-treated recipients and 15 1:1 clinically matched comparable controls). Baseline demographic, transplant-related, renal, and glycemic characteristics were broadly comparable between groups. Proteinuria decreased more in the dapagliflozin group than in controls (median change, - 157 [- 310 to - 52] vs. -12 [- 48 to + 25] mg/day; Hodges-Lehmann location-shift estimate, - 171 mg/day; 95% CI, - 310 to - 32; p = 0.009), while eGFR remained stable (between-group difference in ΔeGFR, + 1.6 mL/min/1.73 m²; 95% CI, - 1.8 to + 5.0; p = 0.31). HbA1c decreased from 8.10% (65 mmol/mol) to 7.10% (54 mmol/mol) in the dapagliflozin group, whereas it decreased from 8.18% (66 mmol/mol) to 7.80% (62 mmol/mol) in controls. Greater reductions were also observed in fasting plasma glucose and daily insulin dose. Two urinary tract infections requiring oral antibiotics occurred in the dapagliflozin group and one in controls. No genital infections, diabetic ketoacidosis, acute rejection, graft loss, cardiovascular events, severe infections requiring hospitalization, or deaths were observed.

conclusionsIn this exploratory 1:1 clinically matched cohort of selected diabetic kidney transplant recipients, dapagliflozin use was associated with reduced proteinuria, improved glycemic measures, and lower treatment burden over 12 months, without observed major graft-related or serious infectious events. However, the retrospective design, small sample size, selected cohort, and treatment-completer efficacy analysis preclude causal inference and definitive safety conclusions. Larger prospective multicenter studies are required before routine implementation in transplant practice can be recommended.