Clinical Investigation

Kidney International (1992) 41, 1653–1661; doi:10.1038/ki.1992.238

Impaired metabolism of high density lipoprotein in uremic patients

Tetsuo Shoji1, Yoshiki Nishizawa1, Hiroshi Nishitani1, Makoto Yamakawa1 and Hirotoshi Morii1

1Second Department of Internal Medicine, Osaka City University Medical School, and Kidney Center, Shirasagi Hospital, Osaka, Japan

Correspondence: Yoshiki Nishizawa MD, Second Department of Internal Medicine, Osaka City University Medical School, 1-5-7, Asahi-machi, Abeno-ku, Osaka 545, Japan.

Received 10 September 1991; Revised 21 January 1992; Accepted 24 January 1992.

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Abstract

Impaired metabolism of high density lipoprotein in uremic patients. We measured lipoproteins, apolipoproteins, lipoprotein lipase (LPL), hepatic triglyceride lipase (HTGL), lecithin: cholesterol acyltransferase (LCAT) and parameters of calcium metabolism to evaluate the roles of these enzymes and hypertriglyceridemia for impaired high-density lipoprotein (HDL) metabolism in chronic renal failure, and to examine the impact of altered calcium homeostasis on the lipoprotein-regulating enzymes. The subjects were 25 healthy volunteers and 66 uremic patients, 24 treated with hemodialysis (HD) and 42 with continuous ambulatory peritoneal dialysis (CAPD). Lipoprotein analysis revealed: (1) reduction in HDL cholesterol especially in HDL2 subfraction; (2) increase in HDL triglyceride; and (3) decreased ratio of HDL2 cholesterol to HDL3 cholesterol in both HD and CAPD patients. Simple regression analysis showed: (1) a positive correlation between VLDL triglyceride and triglycéride/cholestérol ratio of HDL; (2) positive correlations of LPL level in post-heparin plasma to cholesterol concentrations in HDL2, HDL3 and total HDL, and to apolipoproteins A-I and A-II; and (3) inverse correlations of HTGL to HDL2 cholesterol and to the ratio of HDL2 cholesterol/HDL3 cholesterol. Multiple regression analysis of HDL cholesterol indicated positive association with LPL and inverse correlation with VLDL triglyceride. Four variables including LPL, HTGL, LCAT and VLDL triglyceride explained 51.5% of the variation of HDL cholesterol. HDL2 cholesterol was associated positively with LPL and negatively with VLDL triglyceride in the model. HDL3 cholesterol was associated positively with LPL, HTGL and LCAT and inversely with VLDL triglyceride. Stepwise multiple regression analysis indicated that independent predictors of HTGL were gender, parathyroid hormone levels by a mid-portion assay, ionized calcium and age, and that those of LCAT were ionized calcium and age. These results suggest that elevated VLDL and alterations in the enzyme levels contributed to deranged HDL metabolism in uremic patients, and that changes in the enzyme levels were associated with impaired calcium homeostasis.

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