Effects of Exogenous Ketosis on Proteinuria and Renal Function

Background: Until recently, the only treatment shown to slow progression of chronic kidney disease (CKD) has been angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). The use of sodium glucose transporter 2 (SGLT2)-inhibitors, which work by blocking the activity of sodium-glucose-cotransporter 2 channels in the proximal kidney tubule, has completely transformed the treatment of proteinuric kidney disease, with a 28% decrease in the risk for cardiorenal outcomes. Despite these new treatment options, a significant proportion of patients still succumb to kidney failure, require hospitalization for heart failure and die prematurely. Thus, additional preventive measures are essential. Renewed interest in the physiological role of ketone bodies (KB) has emerged. It has become increasingly clear that ketosis has several beneficial effects including anti-epileptic effects, improved exercise capacity, lipid profile, cardiac function and cognition. However, only few clinical studies have studied renal effects of exogenous ketosis, and to our knowledge there are no clinical studies examining the effects long term effects of renal ketosis in patients with CKD. Hypothesis: Ketosis decreases urine albumin to creatinine ratio (ACR) and glomerular filtration rate (GFR) in patients with CKD/PKD. Methods: A randomized, placebo-controlled, double-blinded crossover study will be conducted. Twenty-nine patients with proteinuric kidney disease (study a) and 14 patients with PKD (study b) will receive ketone bodies (Ketone-IQ) and placebo in a randomized order. Each treatment period is four weeks. There will be a wash-out period of two weeks in between treatment periods. Effect variables will be measured in the last day of each treatment period. Perspectives: The study has the potential to provide information regarding the therapeutic potential of ketone bodies in patients with CKD/PKD.