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Investigating the Role of Ketone Body Metabolism in Diabetic Kidney Disease Category: Screening & Prevention of Renal Disease

Rami Al Batran
Université de Montréal
Krescent New Investigator Award
2022 - 2025
$198,783
Screening & Prevention of Renal Disease

In partnership with the Fonds de recherche du QC – Société et culture (FRQSC)  and The Kidney Foundation of Canada.

Lay Abstract

Diabetic kidney disease (DKD) is the major cause of kidney failure worldwide, and many diabetic patients will eventually require dialysis and/or kidney transplantation. Hence, DKD imposes an enormous burden on our health care system and patients’ quality of life. DKD is a multifaceted condition associated with hyperglycemia and hypertension. Therefore, intensive management of DKD is required for most patients with diabetes. Despite intensive diabetes care, the prevalence of DKD remains high, and the current clinical management of DKD stabilizes but does not improve kidney function, indicating a substantial treatment gap. Therefore, there remains an unmet need for innovative treatment strategies to prevent, improve, treat and reverse DKD. Ketone bodies are important fuels for the kidneys, however, their role and function in DKD is ill-defined. The main goal of this research program is to understand whether changes in kidney ketone body metabolism contribute to the development of DKD, and whether we can correct/reverse these changes to treat DKD. To carry out this research program, our laboratory will create genetically modified mice that have reduced ketone body oxidation only in the kidneys. Afterward, we will test whether our genetically modified mice are protected against the development of DKD when fed a diet enriched in fat combined with administration of toxic chemical that causes diabetes over time. We will also test whether augmenting kidney ketone body production via feeding diabetic mice a ketogenic diet or ketone supplement reduces the incidence of DKD and slow its progression in these mice. These experimental approaches will help us to understand whether changes in kidney ketone body metabolism contribute to the development of DKD, and to determine whether a ketogenic diet or ketone supplement can be used as an approach to treat DKD. It is our hope that the ideas put forth in this program will bring new ways of thinking into the field of kidney ketone body metabolism and will lead to exciting new therapies to treat DKD, which is the ultimate goal of this research program. Finally, this research program undoubtedly will benefit a wide spectrum of the Canadian population, including patients, physicians, and nutritionists.