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


METHODS
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]).


METHODS
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
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.
Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
Rakhi P
RP
Naik
Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina Kidney Center, University of North Carolina at Chapel Hill.
Vimal K
VK
Derebail
Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
Morgan E
ME
Grams
Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill.
Nora
N
Franceschini
Department of Biostatistics, Zilber School of Public Health, University of Wisconsin-Milwaukee.
Paul L
PL
Auer
Center for Human Genetic Research, Boston and Broad Institute, Program in Medical and Population Genetics, Massachusetts General Hospital, Cambridge.
Gina M
GM
Peloso
Division of Nephrology, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle.
Bessie A
BA
Young
Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada.
Guillaume
G
Lettre
Division of Nephrology, Department of Medicine, University of California, San Francisco.
Carmen A
CA
Peralta
Kidney Research Institute, University of Washington, Seattle.
Ronit
R
Katz
Stroke Center, Department of Neuroscience, Medical University of South Carolina, Charleston.
Hyacinth I
HI
Hyacinth
Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia.
Rakale C
RC
Quarells
Human Genetics Center, School of Public Health, University of Texas School Health Science Center at Houston.
Megan L
ML
Grove
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge.
Alexander G
AG
Bick
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge.
Pierre
P
Fontanillas
Center for Public Health Genomics, University of Virginia, Charlottesville.
Stephen S
SS
Rich
Department of Genome Sciences, University of Washington, Seattle.
Joshua D
JD
Smith
Human Genetics Center, School of Public Health, University of Texas School Health Science Center at Houston.
Eric
E
Boerwinkle
Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill.
Wayne D
WD
Rosamond
Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge.
Kaoru
K
Ito
Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland.
Sophie
S
Lanzkron
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
Josef
J
Coresh
Department of Medicine and Pediatrics, University of Mississippi Medical Center, Jackson.
Adolfo
A
Correa
Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin, Madison.
Gloria E
GE
Sarto
Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill.
Nigel S
NS
Key
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis.
David R
DR
Jacobs
Center for Human Genetic Research, Boston and Broad Institute, Program in Medical and Population Genetics, Massachusetts General Hospital, Cambridge.
Sekar
S
Kathiresan
Division of General Internal Medicine, Department of Medicine, University of California, San Francisco.
Kirsten
K
Bibbins-Domingo
Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina Kidney Center, University of North Carolina at Chapel Hill.
Abhijit V
AV
Kshirsagar
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson.
James G
JG
Wilson
Department of Epidemiology, University of Washington School of Public Health, Seattle.
Alexander P
AP
Reiner
D000328:Adult; D001741:Black or African American / Q000706:statistics & numerical data*; D000368:Aged; D000419:Albuminuria / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000208:ethnology / Q000235:genetics; D012306:Risk; D012805:Sickle Cell Trait / Q000453:epidemiology* / Q000208:ethnology; D014481:United States / Q000453:epidemiology; D055815:Young Adult