Serum phosphate as an independent factor associated with cholesterol metabolism in patients undergoing hemodialysis: a cross-sectional analysis of the DREAM cohort.

Abstract

Hyperphosphatemia is a risk factor for cardiovascular outcomes in patients with chronic kidney disease. In an experimental model, hyperphosphatemia promoted atherosclerosis by activating sterol regulatory element-binding protein 2, which controls cholesterol homeostasis. In the present study, we hypothesized that serum phosphate level is associated with cholesterol metabolism in patients with kidney failure. We conducted a single-center cross-sectional study including 492 patients undergoing hemodialysis and 100 healthy controls not on statin or ezetimibe treatment. Serum lathosterol and campesterol levels were measured as a marker of cholesterol synthesis and absorption, respectively. As compared with the control group, the hemodialysis patients had higher median phosphate {5.8mg/dL [interquartile range (IQR 5.0-6.6) versus 3.3 (3.0-3.6); P<.001], lower lathosterol [1.2µg/mL (IQR 0.8-1.7) versus 2.6 (1.9-3.4); P<.001] and higher campesterol levels [4.5µg/mL (IQR 3.6-6.0) versus 4.1 (3.2-5.4); P=.02]. Serum phosphate correlated positively to campesterol in the control group (Spearman's r=0.21, P=.03) and in hemodialysis patients (Spearman's r=0.19, P<.001). The positive association between phosphate and campesterol levels in the hemodialysis group remained significant in multivariable-adjusted linear regression analysis. There was no significant association between phosphate and lathosterol in either group. An independent association was found between phosphate and campesterol levels in patients with kidney failure. This study suggests a novel relationship between phosphate and cholesterol metabolism, both of which could affect cardiovascular outcomes in this population.