Research Awards Recipients

Lay Summary

The incidence of diabetic kidney disease (DKD; also known as diabetic nephropathy) has more than doubled in the past decades, largely due to the increasing prevalence of diabetes. Approximately 30 to 40% of all diabetic patients will develop DKD, and many of them will eventually require dialysis and/or kidney transplantation. Thus, DKD imposes an enormous burden on our health care system and patients’ quality of life. 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. Indeed, lifestyle modifications, a combination of dietary interventions and increased physical activity, are frequently recommended to diabetic patients to reduce the incidence of DKD and slow its progression. The ketogenic diet (KD), a high-fat, low-carbohydrate diet with adequate protein, has attracted greater attention recently as a potential weight-loss strategy, likely due to the obesity epidemic. Also, KD has been shown to increase levels of ketone bodies in animals and humans. Ketone bodies are important fuels for the kidneys; however, little is known about their role in the diabetic kidneys. We speculate that increasing circulating ketone bodies via feeding diabetic mice a KD will reduce the incidence of DKD and slow its progression. We will test our hypothesis by inducing diabetes in mice and measuring ketone body metabolism rates in the diabetic kidneys. Then, we will feed these mice a KD and assess its effects on kidney function. These experimental approaches will help us to investigate whether changes in ketone body metabolism contribute to the development of DKD, and to determine whether KD can be used as an approach to reduce the incidence of DKD and slow its progression. It is our hope that the ideas put forth in this study will bring new ways of thinking into the field of ketone body metabolism and will lead to exciting new research directions.