Grant: Project Grant - PA: Nutrition, Metabolism and Diabetes

Peritoneal dialysis is a lifesaving treatment carried out in patients who develop kidney failure. In this procedure, a cleansing fluid called dialysate is passed through a tube placed into a part of the abdomen, known as the peritoneal cavity. The dialysate absorbs waste products and water from blood vessels in the lining of the abdomen, called the peritoneum. Then the fluid is drawn back out of the body and discarded. A major problem with this technique is that in some patients the amount of fluid that is discarded out reduces over a period of time. This leads to accumulation of fluid in the body and to detrimental effects and is called ultrafiltration failure. This happens because of the damage caused to the peritoneum by glucose (sugar) that is present in the dialysate. Canagliflozin blocks glucose channels present in our body. It has been found to reduce glucose uptake by the peritoneum, reduce peritoneal damage, and increase ultrafiltration in animals but has not been studied in humans. In our study, patients undergoing peritoneal dialysis will participate. In the first part of study, patients will either receive canagliflozin or placebo (inactive pill which looks exactly same as canagliflozin) once daily for 5 weeks. Then, patients who earlier received placebo will be given canagliflozin and vice versa for 5 weeks. A third group of patients will receive no treatment. We will assess the function of the peritoneum by measuring glucose in the dialysate at the beginning of the study and after each treatment phase. This study will thus help us understand whether canagliflozin will reduce glucose uptake from the dialysate. In the second part of the study, two thirds of patients will receive canagliflozin for 4 more months while one third of patients will not receive any treatment. We will measure levels of various harmful substances in the dialysate at the beginning and at 6 months. This will help us understand whether canagliflozin can prevent peritoneal damage.