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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:2615.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Delayed In Vivo Catabolism of Intermediate-Density Lipoprotein and Low-Density Lipoprotein in Hemodialysis Patients as Potential Cause of Premature Atherosclerosis

Katsunori Ikewaki; Juergen R. Schaefer; Michael E. Frischmann; Keio Okubo; Tatsuo Hosoya; Seibu Mochizuki; Benjamin Dieplinger; Evi Trenkwalder; Horst Schweer; Florian Kronenberg; Paul Koenig; Hans Dieplinger

From the Divisions of Cardiology (K.I., S.M.) and Nephrology (K.O., T.H.), Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan; the Department of Internal Medicine–Cardiology (J.R.S.) and Children’s Hospital (H.S.), Philipps University, Marburg, Germany; the Division of Genetic Epidemiology (M.E.F., E.T., F.K., H.D.), Department of Medical Genetics, Clinical and Molecular Pharmacology and the Department of Clinical Nephrology (P.K.), Innsbruck Medical University, Innsbruck, Austria; the Department of Laboratory Medicine (B.D.), Konventhospital Barmherzige Brueder, Linz, Austria; and the Institute of Epidemiology (F.K.), GSF-National Research Center for Environment and Health, Neuherberg, Germany.

Correspondence to Hans Dieplinger, Division of Genetic Epidemiology, Department of Medical Genetics, Clinical and Molecular Pharmacology, Innsbruck Medical University, Schoepfstrasse 41, A-6020 Innsbruck, Austria. E-mail hans.dieplinger{at}i-med.ac.at

Objective— Premature cardiovascular disease is the leading cause of death in patients with end-stage renal disease treated by hemodialysis (HD). Low-density lipoprotein (LDL) levels are not generally increased in HD patients, but their LDL metabolism is still poorly understood. We therefore investigated the in vivo metabolism of apoB-containing lipoproteins in two different ethnic populations of HD patients and controls.

Methods and Results— We performed stable isotope kinetic studies using a primed constant infusion of deuterated leucine in 12 HD patients and 13 healthy controls. Tracer/tracee ratio of apoB was determined by means of gas chromatography/mass spectrometry, and the modeling program SAAMII was used to estimate the fractional catabolic rate (FCR) of apoB. Mean LDL-apoB plasma concentrations were almost identical in both groups (HD: 95±30 mg/dL, controls: 91±40 mg/dL), whereas LDL-apoB FCR was 50% lower in HD patients as compared with controls (0.22±0.12 days^–1 versus 0.46±0.20 days^–1, P=0.001) with concomitantly decreased production rates of LDL. Compared with controls, intermediate-density lipoprotein (IDL)-apoB FCR was 65% lower (2.87±1.02 days^–1 versus 8.89±4.94 days^–1, P=0.014), accompanied by 1.5-fold higher IDL-apoB levels in HD. Very low-density lipoprotein metabolism was similar in both study groups.

Conclusions— In vivo catabolism of LDL and IDL is severely impaired in HD patients but misleadingly masked by normal plasma cholesterol levels. The resulting markedly prolonged residence times of both IDL and LDL particles might thus significantly contribute to the well-documented high risk for premature cardiovascular disease in HD patients.

The metabolism of atherogenic LDL in hemodialysis (HD) patients who are at high risk for cardiovascular disease (CVD) is still poorly understood. We here report a severely impaired catabolism of LDL and IDL (misleadingly masked by normal plasma cholesterol levels) in 12 HD patients compared with 13 controls, investigated by stable-isotope technology. The resulting markedly prolonged residence times of both IDL and LDL particles might thus significantly contribute to the well-documented high risk for premature CVD in HD patients.

Key Words: cardiovascular diseases • isotopes • kidney • lipoproteins • metabolism

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