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Apolipoprotein E and progression of chronic kidney disease.

TitleApolipoprotein E and progression of chronic kidney disease.
Publication TypeJournal Article
Year of Publication2005
AuthorsHsu CC, Kao LWH, Coresh J, Pankow JS, Marsh-Manzi J, Boerwinkle E, Bray MS
JournalJAMA
Volume293
Issue23
Pagination2892-9
Date Published2005 Jun 15
ISSN1538-3598
KeywordsAfrican Continental Ancestry Group, Apolipoproteins E, Chronic Disease, Diabetes Mellitus, Disease Progression, European Continental Ancestry Group, Female, Follow-Up Studies, Genotype, Humans, Kidney Diseases, Male, Middle Aged, Multivariate Analysis, Risk Factors
Abstract

CONTEXT: Apolipoprotein E (APOE) genetic variation has been implicated in diabetic nephropathy with the epsilon2 allele increasing and the epsilon4 allele decreasing risk. APOE allelic associations with chronic kidney disease beyond diabetic nephropathy are unknown, with no studies reported in high-risk African American populations.

OBJECTIVE: To quantify the risk of chronic kidney disease progression associated with APOE in a population-based study including white, African American, diabetic, and nondiabetic individuals.

DESIGN, SETTING, AND PARTICIPANTS: Prospective follow-up (through January 1, 2003) of Atherosclerosis Risk in Communities (ARIC) study participants, including 3859 African American and 10,661 white adults aged 45 to 64 years without severe renal dysfunction at baseline in 1987-1989, sampled from 4 US communities.

MAIN OUTCOME MEASURES: Incident chronic kidney disease progression, defined as hospitalization or death with kidney disease or increase in serum creatinine level of 0.4 mg/dL (35 micromol/L) or more above baseline, examined by APOE genotypes and alleles.

RESULTS: During median follow-up of 14 years, chronic kidney disease progression developed in 1060 individuals (incidence per 1000 person-years: 5.5 overall; 8.8 in African Americans and 4.4 in whites). Adjusting for major chronic kidney disease risk factors, epsilon2 moderately increased and epsilon4 decreased risk of disease progression (likelihood ratio test, P = .03). Further adjustment for low- and high-density lipoprotein cholesterol and triglycerides did not attenuate relative risks (RRs) (epsilon2: 1.08 [95% CI, 0.93-1.25] and epsilon4: 0.85 [95% CI, 0.75-0.95] compared with epsilon3; likelihood ratio test, P = .008). Epsilon4 decreased risk of end-stage renal disease (RR, 0.60 [95% CI, 0.43-0.84]). Epsilon2 was associated with a decline in renal function (RR, 1.25 [95% CI, 1.02-1.53]), though not with events, such as hospitalizations or end-stage renal disease. Risks were similar stratified by race, sex, diabetes, and hypertension (all P values for interaction >.05). Excess risk of chronic kidney disease in African Americans was not explained by APOE alleles.

CONCLUSIONS: APOE variation predicts chronic kidney disease progression, independent of diabetes, race, lipid, and nonlipid risk factors. Our study suggests that nonlipid-mediated pathways, such as cellular mechanisms of kidney remodeling, may be involved in the association of APOE alleles and progression of chronic kidney disease.

DOI10.1001/jama.293.23.2892
Alternate JournalJAMA
PubMed ID15956634
Grant List5T32HL007024 / HL / NHLBI NIH HHS / United States
HL73366 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
UR6/CCU617218 / CC / ODCDC CDC HHS / United States