Delayed in vivo catabolism of intermediate-density lipoprotein and low-density lipoprotein in hemodialysis patients as potential cause of premature atherosclerosis.
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.


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.
Ikewaki
Katsunori
K
Division of Cardiology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Schaefer
Juergen R
JR
Frischmann
Michael E
ME
Okubo
Keio
K
Hosoya
Tatsuo
T
Mochizuki
Seibu
S
Dieplinger
Benjamin
B
Trenkwalder
Evi
E
Schweer
Horst
H
Kronenberg
Florian
F
Koenig
Paul
P
Dieplinger
Hans
H
D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D050197:Atherosclerosis / Q000453:epidemiology / Q000209:etiology* / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D015243:Cholesterol, VLDL / Q000097:blood; D003903:Deuterium; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000493:pharmacokinetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000378:metabolism* / Q000628:therapy; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011994:Recombinant Proteins; D006435:Renal Dialysis; D012307:Risk Factors
D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D008074:Lipoproteins; D011994:Recombinant Proteins; C030104:lipoprotein cholesterol; C081222:sargramostim; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D002784:Cholesterol; D003903:Deuterium