#2578 Safety profile of dapagliflozin therapy in the kidney peritransplant period

Abstract

Abstract Background and Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a class of glucose-lowering drugs that have demonstrated important cardio- and nephroprotective effects. These effects, according to preclinical data, may include attenuation of ischemia/reperfusion injury due to downregulation of pro-inflammatory cytokines and necroptosis mediators. This effect could be critical in the peritransplant period, protecting the allograft and potentially reducing delayed graft function (DGF). However, administration of SGLT2i immediately after deceased-donor kidney transplantation (KTx) could potentially be associated with adverse outcomes, such as urinary tract infections (UTI). We report the results of the first 10 patients of an ongoing study aimed at describing the safety profile of dapagliflozin in the peri-KTx period. Method Prospective, uncontrolled pilot study of consecutive, incident KTx patients that received a daily dose of dapagliflozin 10 mg, starting immediately before surgery and continuing until completing the first week post-transplant. All subjects provided informed consent for the study. Those with liver dysfunction, known allergy to SGLT2i, programmed for live-donor or multiorgan kidney transplantation or unable to provide informed consent were excluded. The primary outcome was the development of UTI during index hospitalization, defined either as a positive urine culture and/or symptoms suggestive of UTI. For comparison purposes, a retrospective sample of age- and sex-matched patients that received a KTx prior to the start of this study was included in this analysis. Two controls were selected for each case. Results Demographics and clinical characteristics of both patients in the study and retrospective controls are summarized in Fig. 1. Recipients that received dapagliflozin had similar rates of UTI when compared to controls, and were prescribed less frequently antibiotic therapy for UTI, although none of these differences reached statistical significance. Most cases of both groups consisted in asymptomatic bacteriuria. Of all four cases of documented UTI among treated patients, only one subject developed UTI during the days of dapagliflozin administration (the first 7 days after surgery). This patient did not require antibiotic therapy. The other three cases developed UTI after dapagliflozin discontinuation. Conclusion Results of this preliminary and limited experience lead us to believe that dapagliflozin in the peritransplant period may be a safe and feasible therapy that could help protect the renal allograft from ischemia/reperfusion injury.