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JAMA. 2014 Nov 26;312(20):2115-25. doi: 10.1001/jama.2014.15063.

Association of sickle cell trait with chronic kidney disease and albuminuria in African Americans.

Author information

1
Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
2
Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina Kidney Center, University of North Carolina at Chapel Hill.
3
Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
4
Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill.
5
Department of Biostatistics, Zilber School of Public Health, University of Wisconsin-Milwaukee.
6
Center for Human Genetic Research, Boston and Broad Institute, Program in Medical and Population Genetics, Massachusetts General Hospital, Cambridge.
7
Division of Nephrology, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle.
8
Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada.
9
Division of Nephrology, Department of Medicine, University of California, San Francisco.
10
Kidney Research Institute, University of Washington, Seattle.
11
Stroke Center, Department of Neuroscience, Medical University of South Carolina, Charleston.
12
Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia.
13
Human Genetics Center, School of Public Health, University of Texas School Health Science Center at Houston.
14
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge.
15
Center for Public Health Genomics, University of Virginia, Charlottesville.
16
Department of Genome Sciences, University of Washington, Seattle.
17
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
18
Department of Medicine and Pediatrics, University of Mississippi Medical Center, Jackson.
19
Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin, Madison.
20
Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill.
21
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis.
22
Division of General Internal Medicine, Department of Medicine, University of California, San Francisco.
23
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.
24
Department of Epidemiology, University of Washington School of Public Health, Seattle.

Abstract

IMPORTANCE:

The association between sickle cell trait (SCT) and chronic kidney disease (CKD) is uncertain.

OBJECTIVE:

To describe the relationship between SCT and CKD and albuminuria in self-identified African Americans.

DESIGN, SETTING, AND PARTICIPANTS:

Using 5 large, prospective, US population-based studies (the Atherosclerosis Risk in Communities Study [ARIC, 1987-2013; n = 3402], Jackson Heart Study [JHS, 2000-2012; n = 2105], Coronary Artery Risk Development in Young Adults [CARDIA, 1985-2006; n = 848], Multi-Ethnic Study of Atherosclerosis [MESA, 2000-2012; n = 1620], and Women's Health Initiative [WHI, 1993-2012; n = 8000]), we evaluated 15,975 self-identified African Americans (1248 participants with SCT [SCT carriers] and 14,727 participants without SCT [noncarriers]).

MAIN OUTCOMES AND MEASURES:

Primary outcomes were CKD (defined as an estimated glomerular filtration rate [eGFR] of <60 mL/min/1.73 m2 at baseline or follow-up), incident CKD, albuminuria (defined as a spot urine albumin:creatinine ratio of >30 mg/g or albumin excretion rate >30 mg/24 hours), and decline in eGFR (defined as a decrease of >3 mL/min/1.73 m2 per year). Effect sizes were calculated separately for each cohort and were subsequently meta-analyzed using a random-effects model.

RESULTS:

A total of 2233 individuals (239 of 1247 SCT carriers [19.2%] vs 1994 of 14,722 noncarriers [13.5%]) had CKD, 1298 (140 of 675 SCT carriers [20.7%] vs 1158 of 8481 noncarriers [13.7%]) experienced incident CKD, 1719 (150 of 665 SCT carriers [22.6%] vs 1569 of 8249 noncarriers [19.0%]) experienced decline in eGFR, and 1322 (154 of 485 SCT carriers [31.8%] vs 1168 of 5947 noncarriers [19.6%]) had albuminuria during the study period. Individuals with SCT had an increased risk of CKD (odds ratio [OR], 1.57 [95% CI, 1.34-1.84]; absolute risk difference [ARD], 7.6% [95% CI, 4.7%-10.8%]), incident CKD (OR, 1.79 [95% CI, 1.45-2.20]; ARD, 8.5% [95% CI, 5.1%-12.3%]), and decline in eGFR (OR, 1.32 [95% CI, 1.07-1.61]; ARD, 6.1% [95% CI, 1.4%-13.0%]) compared with noncarriers. Sickle cell trait was also associated with albuminuria (OR, 1.86 [95% CI, 1.49-2.31]; ARD, 12.6% [95% CI, 7.7%-17.7%]).

CONCLUSIONS AND RELEVANCE:

Among African Americans in these cohorts, the presence of SCT was associated with an increased risk of CKD, decline in eGFR, and albuminuria, compared with noncarriers. These findings suggest that SCT may be associated with the higher risk of kidney disease in African Americans.

PMID:
25393378
PMCID:
PMC4356116
DOI:
10.1001/jama.2014.15063
[Indexed for MEDLINE]
Free PMC Article

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