Cardiovascular and Renal Protection with SGLT2 Inhibition in Kidney Transplant Recipients (RENAISSANCE) - PROJECT ABSTRACT Compared with dialysis, kidney transplant recipients have significantly better survival and quality of life. In the last 2 decades, short-term posttransplant patient and kidney transplant survival have improved. However, there has not been a similar improvement in long-term survival. Within 10 years after a kidney transplant, about 47% of deceased donor and about 30% of living donor transplants have failed. The 2 most common cause of late kidney transplant failure are: a) premature death despite adequate kidney transplant function; and b) slow progressive decline in function of the transplant, eventually resulting in kidney failure. Our goal is to improve long-term outcomes after kidney transplantation. In the general population, for patients with cardiovascular disease, heart failure and/or chronic kidney disease, a new class of drugs, sodium-glucose cotransporter-2 inhibitors (SGLT2i), significantly reduce death, cardiovascular disease and progression of native kidney disease. Thus, these drugs may have a major impact on the two most common reasons for late posttransplant kidney failure. This class of drugs are now recommended for persons in the general population with heart disease and/or chronic kidney disease. However, for immunosuppressed kidney transplant recipients there has been concern about whether these drugs will have similar benefits, and whether there will be an unacceptable risk of side effects. As a result, kidney transplant recipients have been excluded from large randomized trials of SGLT2is. Because of the concerns about the efficacy and side effects of these drugs in transplant recipients, and the lack of information from large trials, reviews and national and international medical guidelines state that before recommending SGLT2is for transplant recipients, large long-term randomized trials need to be done. We propose a prospective randomized trial (n=900) of a SGLT2i (dapagliflozin), compared with placebo, to study efficacy and safety of this drug in kidney transplant recipients. Enrolled participants will be followed for a minimum of 3 years. Our hypothesis is that dapagliflozin will be safe in kidney transplant recipients and will reduce death and cardiovascular disease while prolonging kidney transplant function. To maximize enrollment and diversity, we plan a pragmatic trial with no extra visits to the transplant center and minimal study-related laboratory tests. This will facilitate participation for those at long distances from a transplant center and/or those with difficulty in finding transportation. This trial represents a unique opportunity to profoundly impact the care of kidney transplant recipients. Showing that dapagliflozin improves survival after a transplant and reduces cardiovascular disease and progression of kidney disease will transform clinical care in this high-risk population.
