Abstract
BACKGROUND: Circulating lipoproteins and their protein constituents, apolipoproteins, are risk factors for chronic kidney disease (CKD). The associations between apolipoprotein A1, apolipoprotein B and their ratio with glomerular filtration rate estimated from the new CKD Epidemiology Collaboration (CKD-EPI) equation (eGFR) are not well studied in the general population. METHODS: Associations between apolipoprotein A1, B and their ratio with the outcomes of eGFR, CKD (eGFR<60 mL/min/1.73 m2) and albuminuria were examined in the Atherosclerosis Risk in Communities study (ARIC, n=10,292, 1996-98) and the Third National Health and Nutrition Examination Survey (NHANES III, n=7023, 1988-91). Cross-sectional multivariable-adjusted analyses were performed using linear and logistic regression. Prospective analyses related baseline apolipoprotein levels to subsequent CKD incidence over 10 years using the ARIC Carotid MRI follow-up cohort (n=1659). RESULTS: Higher apolipoprotein A1 quartiles were associated with a lower prevalence of CKD [Q4 versus Q1: odds ratio (OR) 0.73, P-trend=0.02 in ARIC; Q4 versus Q1: OR 0.53, P-trend<0.01 in NHANES III] as well as with higher eGFR (P-trend<0.01 in ARIC and NHANES III). No consistent significant associations were found for apolipoprotein B in either study. The apolipoprotein B/A1 ratio was significantly associated with eGFR across quartiles in both studies (P-trend<0.01) and with CKD in ARIC (Q4 versus Q1: OR 1.23, P-trend=0.01). Prospectively, there were trends for the association of apolipoproteins with incident CKD [Q4 versus Q1: incidence rate ratio (IRR)=0.68 for apolipoprotein A1, P-trend=0.1; Q4 versus Q1: IRR=1.35 for apolipoprotein B, P-trend=0.2]. Associations were not systematically stronger when comparing traditional lipids (total cholesterol, low-density lipoprotein or high-density lipoprotein) to apolipoproteins. CONCLUSIONS: Higher serum apolipoprotein A1 was associated with lower prevalence of CKD and higher eGFR estimated by the CKD-EPI equation in two large multiethnic population-based samples. While apolipoprotein B showed no consistent associations, a higher apolipoprotein B/A1 ratio was significantly associated with lower eGFR in both studies. The direction and magnitude of the longitudinal associations between apolipoproteins and CKD incidence were overall similar to those observed cross-sectionally. No consistent differences became apparent between traditional lipids and apolipoproteins.