Markers of cholesterol metabolism and cardiovascular outcomes in patients with chronic kidney disease
Abstract Background In dialysis patients statins are less effective than in other high risk patients due to a shift from cholesterol synthesis towards cholesterol absorption. The CARE FOR HOMe study investigates whether a shift towards cholesterol absorption occurs in non-dialysis chronic kidney disease (CKD), and whether the ratio of campesterol-to-lathosterol predicts cardiovascular outcomes in non-dialysis CKD patients. Methods In this analysis 251 participants suffering from CKD (KDIGO 2–4) without lipid-lowering drugs were included and followed for major atherosclerotic events (MACE). Additionally, all-cause death and the composite endpoint MACE and all-cause death were explored. We performed univariate and multivariate Cox regression analysis, adjusting for age, gender, estimated glomerular filtration rate (eGFR), log-transformed albuminuria, prevalent cardiovascular disease, current smoking, diabetes mellitus, systolic blood pressure and body mass index. The primary hypothesis was that patients with a high campesterol-to-lathosterol ratio had a higher event rate. Results Neither lathosterol-to-cholesterol (r=0.022; p=0.730), nor campesterol-to-cholesterol (r=0.041; p=0.519) nor campesterol-to-lathosterol (r=−0.103; p=0.105) correlated with eGFR. During follow-up of 5.1±2.1 years, 47 participants suffered from MACE, 46 participants died and 61 reached the composite endpoint of MACE or all-cause death. In univariate Cox regression analysis, campesterol-to-lathosterol did not predict atherosclerotic cardiovascular events (HR 0.740; 0.368–1.487), all-cause death (HR 0.564; 0.277–1.145) or the composite endpoint (HR 0.652; 0.355–1.196). After full adjustment: campesterol-to-lathosterol was not associated with all three endpoints; MACE (HR 1.064; 0.507–2.231), all-cause death (HR 0.818; 0.420–1.594) and MACE and all-cause death (HR 0.956; 0.525–1.744). Conclusion Markers of cholesterol metabolism were not associated with eGFR in patients with impaired renal function (KDIGO 2–4). Campesterol-to-lathosterol did not predict future MACE or all-cause death in non-dialysis CKD. These findings do not support the concept that patients with impaired renal function (KDIGO 2–4) benefit in particular from ezetimibe treatment. Further research is required to address this hypothesis in dialysis patients. Funding Acknowledgement Type of funding source: None