Association of Sickle Cell Trait With Chronic Kidney Disease and Albuminuria in African Americans | Chronic Kidney Disease | JAMA | JAMA Network
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Original Investigation
November 26, 2014

Association of Sickle Cell Trait With Chronic Kidney Disease and Albuminuria in African Americans

Author Affiliations
  • 1Division of Hematology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
  • 2Division of Nephrology and Hypertension, Department of Medicine, University of North Carolina Kidney Center, University of North Carolina at Chapel Hill
  • 3Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland
  • 4Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill
  • 5Department of Biostatistics, Zilber School of Public Health, University of Wisconsin-Milwaukee
  • 6Center for Human Genetic Research, Boston and Broad Institute, Program in Medical and Population Genetics, Massachusetts General Hospital, Cambridge
  • 7Division of Nephrology, Department of Medicine, Veterans Affairs Puget Sound Health Care System, University of Washington, Seattle
  • 8Montreal Heart Institute and Université de Montréal, Montréal, Québec, Canada
  • 9Division of Nephrology, Department of Medicine, University of California, San Francisco
  • 10Kidney Research Institute, University of Washington, Seattle
  • 11Stroke Center, Department of Neuroscience, Medical University of South Carolina, Charleston
  • 12Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia
  • 13Human Genetics Center, School of Public Health, University of Texas School Health Science Center at Houston
  • 14Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge
  • 15Center for Public Health Genomics, University of Virginia, Charlottesville
  • 16Department of Genome Sciences, University of Washington, Seattle
  • 17Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
  • 18Department of Medicine and Pediatrics, University of Mississippi Medical Center, Jackson
  • 19Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin, Madison
  • 20Division of Hematology and Oncology, Department of Medicine, University of North Carolina at Chapel Hill
  • 21Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis
  • 22Division of General Internal Medicine, Department of Medicine, University of California, San Francisco
  • 23Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson
  • 24Department of Epidemiology, University of Washington School of Public Health, Seattle
JAMA. 2014;312(20):2115-2125. doi:10.1001/jama.2014.15063
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.

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