Association of Ketone Bodies with Incident CKD and Death: A UK Biobank Study

Aims Although cellular and animal models have suggested a protective effect of ketone bodies (KBs), clinical data are still lacking to support these findings. This study aimed to investigate the association of KB levels with incident chronic kidney disease (CKD) and death. Methods This was a prospective cohort study of 87,899 UK Biobank participants without baseline CKD who had plasma levels of β-hydroxybutyrate, acetoacetate, and acetone levels measured at the time of enrollment. The main predictor was plasma total KB, which was the sum of the aforementioned three KBs. The primary outcome was a composite of incident CKD, or all-cause mortality. Secondary outcomes included the individual components of the primary outcome. Results During a median follow-up of 11.9 years, a total of 8,145 primary outcome events occurred (incidence rate 8.0/1,000 person-years). In the multivariable Cox model, a 1-standard deviation increase in log total KB was associated with a 7% [adjusted hazard ratio (aHR), 1.07; 95% confidence interval (CI), 1.05-1.10] higher risk of the primary outcome. When stratified into quartiles, the aHR (95% CI) for Q4 versus Q1 was 1.18 (1.11-1.27). This association was consistent for incident CKD (aHR, 1.04; 95% CI, 1.01-1.07), and all-cause mortality (aHR, 1.10; 95% CI, 1.07-1.13). Compared with Q1, Q4 was associated with a 12% (aHR 1.12; 95% CI 1.02-1.24) and 26% (aHR 1.26; 95% CI 1.15-1.37) higher risk of incident CKD and all-cause mortality, respectively. Conclusions Higher KB levels were independently associated with higher risk of incident CKD and death.