The Role of Ketone Bodies in Various Animal Models of Kidney Disease

Abstract

The kidney is a vital organ that carries out significant metabolic functions in our body. Due to the complexity of its role, the kidney is also susceptible to many disease conditions, such as acute kidney injury (AKI) and chronic kidney disease (CKD). Despite the prevalence and our increased understanding of the pathophysiology of both AKI and CKD as well as the transition of AKI to CKD, no well-established therapeutics have been applied clinically to these conditions, rendering an urgent need for a novel potential therapeutic target to be developed. In this article, we reviewed the function of ketone bodies in some common kidney conditions, such as drug-induced nephrotoxicity, ischemia and reperfusion injury, fibrosis development, diabetic kidney disease, kidney aging, hypertension, and CKD progression. All the selected studies reviewed were performed in animal models by primarily utilizing rodents, which also provide invaluable sources for future clinical applications. Ketone bodies have shown significant renal protective properties via attenuation of oxidative stress, increased expression of anti-inflammatory proteins, gene regulation, and a reduction of apoptosis of renal cells. A physiological level of ketone bodies could be achieved by fasting, a ketogenic diet, and an exogenous ketone supplement. Finally, the limitations of the long-term ketogenic diet were also discussed.