Project Description Narrative:
It is estimated that nearly 15% of the adult United States population has chronic kidney disease (CKD), which is a progressive pathological loss of kidney function. The kidneys have an essential role in both handling the nutrients brought into the body through eating and drinking, as well as removing wastes produced by metabolic processes from the blood. Kidneys are also responsible for long-term control of blood pressure through elimination of ingested salt and water. In the state of Wisconsin, CKD is the tenth leading cause of death in adults.
There is no cure for CKD. Therapies for patients with CKD are limited and primarily focus on controlling high blood pressure and diabetes, both of which are prevalent comorbidities associated with CKD and progression to end-stage kidney disease (ESKD). Approximately 12,000 Wisconsinites are living with ESKD (i.e., kidney failure), which means they must undergo dialysis therapy or receive kidney transplant to survive. Dialysis therapy and kidney transplants are burdensome in terms of health care costs, lost wages for patients and their caretakers, and negatively impact quality of life. While renal transplant can provide long-term survival, there simply aren’t enough kidneys available for transplant with roughly 1,300 Wisconsinites on the kidney transplant waiting list. New accessible and low-cost approaches for delaying CKD onset and progression to ESRD are needed in Wisconsin and throughout the country.
Research performed at MCW and elsewhere has shown that during CKD progression the ability of some kidney and cardiac cells to use fatty acid as an energy source declines and that therapeutic drugs, called fibrates, that stimulate cellular fat utilization, can reduce blood pressure, kidney damage, and cardiovascular damage in rodent models of CKD. Despite promise in animal models, prescription of fibrates for people living with CKD is done cautiously because damaged kidneys cannot clear these drugs at the appropriate rate. This can result in too much fat utilization, muscle damage, worsened renal injury, and even neurological issues.
This project aims to determine if CKD pathology can be reduced by increasing cellular fat utilization without medications, by simply shortening the window where food is eaten each day.