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

JAMA. 2014 Nov 26;312(20):2115-25. 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.

Publication types

  • Meta-Analysis
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • African Americans / statistics & numerical data*
  • Aged
  • Albuminuria / epidemiology*
  • Albuminuria / ethnology
  • Albuminuria / genetics
  • Cohort Studies
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Male
  • Middle Aged
  • Prospective Studies
  • Renal Insufficiency, Chronic / epidemiology*
  • Renal Insufficiency, Chronic / ethnology
  • Renal Insufficiency, Chronic / genetics
  • Risk
  • Sickle Cell Trait / epidemiology*
  • Sickle Cell Trait / ethnology
  • United States / epidemiology
  • Young Adult

Grant support