Cholesterol Synthesis, Cholesterol Absorption, and Mortality in Hemodialysis Patients

Background and objectives Recent clinical trials on cholesterol-lowering in patients with CKD yielded conflicting results, which might have resulted from different treatment strategies. Serum cholesterol levels are determined by endogenous synthesis and intestinal absorption, which are differentially influenced by various classes of cholesterol-lowering agents. Assessing markers of cholesterol metabolism has thus been proposed for guidance of lipid-lowering therapy. This study analyzed surrogate markers of cholesterol absorption and synthesis in hemodialysis (HD) patients. Design, setting, participants, & measurements In 113 HD patients, lathosterol was measured as a marker of cholesterol synthesis and cholestanol was measured as a marker of cholesterol absorption via gas chromatography. Controls were 229 healthy persons. Overall survival in HD patients was recorded over 3.4-year follow-up. Results Compared with controls, HD patients had lower lathosterol and higher cholestanol levels (P<0.001 for both). During follow-up, 58 patients died; higher cholestanol (indicating higher cholesterol absorption) predicted poor outcome among HD patients in multivariate Cox regression analysis after adjustment for potential confounders (hazard ratio for cholestanol above median, 2.24 [95% confidence interval (CI), 1.29-3.89]; P=0.004), whereas lower lathosterol (indicating lower cholesterol synthesis) did not (hazard ratio for lathosterol below median, 1.43 [95% CI, 0.81-2.50]; P=0.22). Conclusions This analysis of markers of cholesterol metabolism characterizes HD patients as cholesterol absorbers. In longitudinal analysis, higher levels of cholestanol were associated with all-cause mortality. Clin J Am Soc Nephrol 7: 943-948, 2012. doi: 10.2215/CJN.05170511