Kidney Transplant Failure

The goal of this clinical trial is to look at the effect of SGLT2 (Sodium glucose transporter 2) inhibition in patients receiving a kidney-transplant 6 weeks earlier at Oslo University hospital. Rikshospitalet. Investigators will search for answers along three pathways: Can SGLT2 inhibitor 1) preserve glomerular filtration rate (GFR), 2) reduce interstitial fibrosis in the kidney, and 3) favorably improve metabolic risk factors for graft failure such as visceral obesity, glucose intolerance and high blood pressure? The participants (N=330) will be randomized to either dapagliflozin 10 mg or placebo o.d. in a blinded fashion. Researchers will than use kidney transplant biopsies, measured GFR, blood pressure sampling, glucose tolerance test (OGTT), dual-energy X-ray absorptiometry (DXA scan) and estimated GFR from the two groups in comparison, to evaluate the effect treatment. The participants will be followed for a total of 3 years.

Kidney transplant is often the best treatment for people with kidney failure, but transplanted kidneys don't always last a lifetime. Many transplanted kidneys fail within 12 years, leaving patients needing dialysis or another transplant. One major issue is something called "allosensitization," which happens when the immune system attacks the donated kidney due to foreign markers on the kidney. This makes it harder to match a patient with another donor kidney in the future. To try to prevent this, patients are given immunosuppressants (drugs that weaken the immune system) after a transplant to stop the immune system from attacking the new kidney. However, after a kidney transplant fails and patients return to dialysis, there's no clear evidence that continuing immunosuppressants helps prevent allosensitization. Plus, these drugs have serious risks, including infections, heart disease, and even cancer. The PART study is a pilot study designed to explore whether continuing immunosuppression after a failed transplant for two years (instead of stopping after six months) can lower the risk of allosensitization and whether it is safe to do so. This pilot will also gather data that will be used for a larger trial in the future. The study will be done at 12 different research centers, and around 96 patients will be enrolled in the pilot trial. The ultimate goal is to better understand if continuing immunosuppressants after transplant failure can make a difference, and whether it's safe enough to proceed to a larger, more definitive trial.