Apolipoprotein E and progression of chronic kidney disease

Charles C. Hsu, W. H Linda Kao, Josef Coresh, James S. Pankow, Jane Marsh-Manzi, Eric Boerwinkle, Molly S. Bray

Research output: Contribution to journalArticle

Abstract

Context: Apolipoprotein E (APOE) genetic variation has been implicated in diabetic nephropathy with the ε2 allele increasing and the ε4 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 μmol/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, ε2 moderately increased and ε4 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) (ε2: 1.08 [95% CI, 0.93-1.25] and ε4: 0.85 [95% CI, 0.75-0.95] compared with ε3; likelihood ratio test, P=.008). ε4 decreased risk of end-stage renal disease (RR, 0.60 [95% CI, 0.43-0.84]). ε2 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.

Original languageEnglish (US)
Pages (from-to)2892-2899
Number of pages8
JournalJournal of the American Medical Association
Volume293
Issue number23
DOIs
StatePublished - Jun 15 2005

Fingerprint

Apolipoproteins E
Chronic Renal Insufficiency
African Americans
Disease Progression
Alleles
Diabetic Nephropathies
Kidney
Chronic Kidney Failure
Hospitalization
Kidney Diseases
HDL Cholesterol
Population
Creatinine
Atherosclerosis
Genotype
Outcome Assessment (Health Care)
Hypertension
Lipids

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hsu, C. C., Kao, W. H. L., Coresh, J., Pankow, J. S., Marsh-Manzi, J., Boerwinkle, E., & Bray, M. S. (2005). Apolipoprotein E and progression of chronic kidney disease. Journal of the American Medical Association, 293(23), 2892-2899. https://doi.org/10.1001/jama.293.23.2892

Apolipoprotein E and progression of chronic kidney disease. / Hsu, Charles C.; Kao, W. H Linda; Coresh, Josef; Pankow, James S.; Marsh-Manzi, Jane; Boerwinkle, Eric; Bray, Molly S.

In: Journal of the American Medical Association, Vol. 293, No. 23, 15.06.2005, p. 2892-2899.

Research output: Contribution to journalArticle

Hsu, CC, Kao, WHL, Coresh, J, Pankow, JS, Marsh-Manzi, J, Boerwinkle, E & Bray, MS 2005, 'Apolipoprotein E and progression of chronic kidney disease', Journal of the American Medical Association, vol. 293, no. 23, pp. 2892-2899. https://doi.org/10.1001/jama.293.23.2892
Hsu, Charles C. ; Kao, W. H Linda ; Coresh, Josef ; Pankow, James S. ; Marsh-Manzi, Jane ; Boerwinkle, Eric ; Bray, Molly S. / Apolipoprotein E and progression of chronic kidney disease. In: Journal of the American Medical Association. 2005 ; Vol. 293, No. 23. pp. 2892-2899.
@article{c9b7182abd364eceb73a582ca4f44203,
title = "Apolipoprotein E and progression of chronic kidney disease",
abstract = "Context: Apolipoprotein E (APOE) genetic variation has been implicated in diabetic nephropathy with the ε2 allele increasing and the ε4 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 μmol/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, ε2 moderately increased and ε4 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) (ε2: 1.08 [95{\%} CI, 0.93-1.25] and ε4: 0.85 [95{\%} CI, 0.75-0.95] compared with ε3; likelihood ratio test, P=.008). ε4 decreased risk of end-stage renal disease (RR, 0.60 [95{\%} CI, 0.43-0.84]). ε2 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.",
author = "Hsu, {Charles C.} and Kao, {W. H Linda} and Josef Coresh and Pankow, {James S.} and Jane Marsh-Manzi and Eric Boerwinkle and Bray, {Molly S.}",
year = "2005",
month = "6",
day = "15",
doi = "10.1001/jama.293.23.2892",
language = "English (US)",
volume = "293",
pages = "2892--2899",
journal = "JAMA - Journal of the American Medical Association",
issn = "0098-7484",
publisher = "American Medical Association",
number = "23",

}

TY - JOUR

T1 - Apolipoprotein E and progression of chronic kidney disease

AU - Hsu, Charles C.

AU - Kao, W. H Linda

AU - Coresh, Josef

AU - Pankow, James S.

AU - Marsh-Manzi, Jane

AU - Boerwinkle, Eric

AU - Bray, Molly S.

PY - 2005/6/15

Y1 - 2005/6/15

N2 - Context: Apolipoprotein E (APOE) genetic variation has been implicated in diabetic nephropathy with the ε2 allele increasing and the ε4 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 μmol/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, ε2 moderately increased and ε4 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) (ε2: 1.08 [95% CI, 0.93-1.25] and ε4: 0.85 [95% CI, 0.75-0.95] compared with ε3; likelihood ratio test, P=.008). ε4 decreased risk of end-stage renal disease (RR, 0.60 [95% CI, 0.43-0.84]). ε2 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.

AB - Context: Apolipoprotein E (APOE) genetic variation has been implicated in diabetic nephropathy with the ε2 allele increasing and the ε4 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 μmol/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, ε2 moderately increased and ε4 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) (ε2: 1.08 [95% CI, 0.93-1.25] and ε4: 0.85 [95% CI, 0.75-0.95] compared with ε3; likelihood ratio test, P=.008). ε4 decreased risk of end-stage renal disease (RR, 0.60 [95% CI, 0.43-0.84]). ε2 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.

UR - http://www.scopus.com/inward/record.url?scp=20444491653&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20444491653&partnerID=8YFLogxK

U2 - 10.1001/jama.293.23.2892

DO - 10.1001/jama.293.23.2892

M3 - Article

C2 - 15956634

AN - SCOPUS:20444491653

VL - 293

SP - 2892

EP - 2899

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0098-7484

IS - 23

ER -