Apolipoprotein A-I, B-100, and B-48 metabolism in subjects with chronic kidney disease, obesity, and the metabolic syndrome

Abstract

The metabolism of apolipoproteins (apo)B-48, B-100, and A-I was studied with a primed constant infusion of deuterium-labeled leucine in the fed state in 3 male individuals with chronic kidney disease (CKD), a glomerular filtration rate (GFR) of 28 to 57 mL/min/1.73 m2, obesity (body mass index [BMI] 33.1), and the metabolic syndrome. Compared to 5 obese controls (BMI 30.1) and 13 non-obese controls (BMI 25.2), these CKD subjects had high plasma levels of triglycerides (TG) (343 +/- 27.5 mg/dL v 144 +/- 34.4 in the obese controls, P < .001) and low apoA-I (86.7 +/- 3.9 mg/dL). An abnormal high-density lipoprotein (HDL) particle subpopulation pattern was found, with low levels of pre beta-1 and alpha1. Compared to the obese controls, very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) apoB-100 levels were elevated 2- to 3-fold, while LDL apoB-100 levels were slightly lower (-7 %) and apoB-48 levels were comparable. The high TG levels were not associated with statistically significant changes in VLDL apoB-100 kinetics, although the production rate (PR) was higher and the fractional catabolic rate (FCR) was lower. The slightly lower LDL apoB-100 levels were accompanied by a significant 3-fold increase in the FCR and a 2.7-fold increase in the PR. The lower apoA-I levels were accompanied by a 1.6-fold increase in the FCR. Compared to the non-obese controls, the PR of apoA-I was increased by 61% and 38%, respectively (P < .001) in CKD and in obese control subjects. In the control subjects, the PR of apoA-I was significantly correlated with the BMI (r = 0.81, P < .0001). The kinetic results are consistent with these hypotheses: (1) CKD is associated with decreased clearance of the TG-rich lipoproteins (TRLs) and increased catabolism of LDL; (2) obesity increases apoB-100 and apoA-I production; and (3) in CKD, TG transfer to HDL, making HDL more susceptible to catabolism, accounts for the low apoA-I levels.