Grant: Project Grant

Kidney transplantation is the optimal treatment for patients with kidney failure as it is associated with increased survival, improved quality of life, and lower costs compared to dialysis. Advances in immunosuppression have led to improvements in short term patient and transplant survival, but there has been limited improvement in long-term outcomes. Early death and transplant failure in kidney transplant recipients (KTR) is due to cardiovascular disease (CVD) and ongoing loss in kidney function due to rejection and non-rejection causes. Current strategies to treat and/or prevent CVD and non-rejection causes of kidney function decline in KTR are based on studies in non-transplant populations. However, these medications have not been shown to prevent death or kidney function loss in studies conducted in KTR, despite their benefits in nontransplant populations. There is a clear need for dedicated studies of new medications in KTR. Sodium-glucose cotransporter (SGLT) inhibitors block the reabsorption of glucose and salt in the kidney. They have emerged as a highly effective treatment for patients with CVD and/or chronic kidney disease (CKD). In CKD patients, SGLT inhibitors prevent major heart complications, decrease risk of death and delay the development of kidney failure. However, these studies excluded transplant patients and use of SGLT inhibitors in KTR has been low due to potential concerns around risk of infection and acute changes in kidney function. The absence of high-quality studies of SGLT inhibitors is potentially denying KTR of the life- altering benefits of these medications. The proposed study will evaluate the use of the SGLT inhibitor sotagliflozin versus placebo in 900 patients with kidney transplants recruited in Canada, Australia and USA, and will provide valuable new information about the effectiveness and safety of SGLT inhibition in KTR. Results of this study will directly impact the care of these patients.