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

Rakhi P. Naik, Vimal K. Derebail, Morgan E. Grams, Nora Franceschini, Paul L. Auer, Gina M. Peloso, Bessie A. Young, Guillaume Lettre, Carmen A. Peralta, Ronit Katz, Hyacinth I. Hyacinth, Rakale C. Quarells, Megan L. Grove, Alexander G. Bick, Pierre Fontanillas, Stephen S. Rich, Joshua D. Smith, Eric Boerwinkle, Wayne D. Rosamond, Kaoru ItoSophie Lanzkron, Josef Coresh, Adolfo Correa, Gloria E. Sarto, Nigel S. Key, David R. Jacobs, Sekar Kathiresan, Kirsten Bibbins-Domingo, Abhijit V. Kshirsagar, James G. Wilson, Alexander P. Reiner

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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], andWomen'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 outcomeswere CKD (defined as an estimated glomerular filtration rate [eGFR] of 60 mL/min/1.73m2 at baseline or follow-up), incident CKD, albuminuria (defined as a spot urine albumin:creatinine ratio of 30mg/g or albumin excretion rate 30mg/24 hours), and decline in eGFR (defined as a decrease of 3 mL/min/1.73m2 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.

Original languageEnglish (US)
Pages (from-to)2115-2125
Number of pages11
JournalJAMA - Journal of the American Medical Association
Volume312
Issue number20
DOIs
StatePublished - Nov 26 2014

ASJC Scopus subject areas

  • Medicine(all)

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    Naik, R. P., Derebail, V. K., Grams, M. E., Franceschini, N., Auer, P. L., Peloso, G. M., Young, B. A., Lettre, G., Peralta, C. A., Katz, R., Hyacinth, H. I., Quarells, R. C., Grove, M. L., Bick, A. G., Fontanillas, P., Rich, S. S., Smith, J. D., Boerwinkle, E., Rosamond, W. D., ... Reiner, A. P. (2014). Association of sickle cell trait with chronic kidney disease and Albuminuria in African Americans. JAMA - Journal of the American Medical Association, 312(20), 2115-2125. https://doi.org/10.1001/jama.2014.15063