Increased concentration of plasma cholesteryl ester transfer protein in nephrotic syndrome: role in dyslipidemia.

Hyperlipidemia is a prominent feature of the nephrotic syndrome. Lipoprotein abnormalities include increased very low and low density lipoprotein (VLDL and LDL) cholesterol and variable reductions in high density lipoprotein (HDL) cholesterol. We hypothesized that plasma cholesteryl ester trans- fer protein (CETP), which influences the distribution of cholesteryl esters among the lipoproteins, might contribute to lipoprotein abnormalities in nephrotic syndrome. Plasma CETP, apolipoprotein and lipoprotein concentrations were measured in 14 consecutive untreated and 7 treated nephrotic patients, 5 patients with primary hypertriglyceridemia, and 18 normolipidemic controls. Patients with nephrotic syndrome dis- played increased plasma concentrations of apoB, VLDL, and LDL cholesterol. The VLDL was enriched with cholesteryl ester (CE), shown by a CEhiglyceride (TG) ratio approximately twice that in normolipidemic or hypertriglyceridemic controls (P < 0.001). Plasma CETP concentration was increased in pa- tients with untreated nephrotic syndrome compared to controls (3.6 vs. 2.3 mg/l, P < 0.001), and was positively correlated with the CE concentration in VLDL (r=0.69, P=0.004) and with plasma apoB concentration (r=0.68, P=0.007). Treatment with corticosteroids resulted in normalization of plasma CETP and of the CE/TG ratio in VLDL. An inverse correlation between plasma CETP and HDL cholesterol was observed in hyper- triglyceridemic nephrotic syndrome patients (7= -0.67, P= 0.03). The dyslipidemia of nephrotic syndrome includes increased levels of apoB-lipoproteins and VLDL that are un- usually enriched in CE and likely to be atherogenic. Increased plasma CETP probably plays a significant role in the enrich- ment of VLDL with CE, and may also contribute to increased concentrations of apoB-lipoproteins and decreased HDL cholesterol in some patients.-Moulin, P., G. B. Appel, H. N. lipoprotein abnormalities observed typically predispose to accelerated atherosclerosis in the general population. These abnormalities include increased concentrations of plasma apoB, increased VLDL and LDL cholesterol, and in some but not all reports, reduced cholesterol concen- tration in HDL or its subfractions (4-6). The patho- physiology of the lipoprotein abnormalities of NS is only partly understood. Animal and cell culture studies have suggested that liver cells of nephrotic animals may over-