Lower HDL-C and apolipoprotein A-I are related to higher glomerular filtration rate in subjects without kidney disease

Abstract

Animal experiments show that the kidney contributes to apolipoprotein (apo)A-I catabolism. We tested relationships of HDL cholesterol (HDL-C) and apo-I with kidney function in subjects without severe chronic kidney disease. Included was a random sample of the general population (part of the PREVEND cohort). Kidney function [estimated glomerular filtration rate (e-GFR) by two well-established equations and creatinine clearance], HDL-C, triglycerides, apoA-I and insulin resistance (HOMAir) were measured in 2,484 fasting subjects (e-GFR>or=45 ml/min/1.73 m2) without macroalbuminuria, cardiovascular disease, diabetes, or the use of anti-hypertensives and/or lipid-lowering agents. HDL-C (r=-0.056 to -0.102, P<0.01 to <0.001) and apo A-I (r=-0.096 to -0.126, P<0.001) were correlated inversely with both GFR estimates and creatinine clearance in univariate analyses. Multiple linear regression analyses also demonstrated inverse relationships of HDL-C and apoA-I with all measures of kidney function even after adjustment for age, sex, waist circumference, HOMAir, triglycerides, and urinary albumin excretion (P=0.053 to 0.004). In conclusion, HDL-C and apoA-I are inversely related to e-GFR and creatinine clearance in subjects without severely compromised kidney function, which fits the concept that the kidney contributes to apoA-I regulation in humans. High glomerular filtration rate may be an independent determinant of a pro-atherogenic lipoprotein profile.

Fig. 1.

Continuous relationships of HDL-C, apoA-I, and apoA-II with e-GFR, calculated with the MDRD formula, analyzed by polynomial regression analysis. (upper, middle, and lower panel, respectively). Lines of best fit (polynomial quadratic) with 95% confidence intervals are shown.

Fig. 2.

HDL-C, apoA-I, and apoA-II (upper, middle, and lower panel respectively) according to quintiles of eGFR estimated by the MDRD-equation. Ranges of e-GFR in the increasing quintiles were: 47–70, 70–77, 77–84, 84–92 and 92–148 ml/min/1.73 m², respectively. HDL-C and apoA-I: * P for trend < 0.001 by one-way ANOVA. ApoA-II, P = 0.83.