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

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.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Peralta reports grant funding from LabCorp. Dr Lanzkron reports funding from Emmaus, Glycomimetrics, and Novartis. Dr Kathiresan reports grant funding from AstraZeneca and Merck and serving on the advisory board for Amarin, Catabasis, and Regeneron. Dr Bibbins-Domingo reports receiving personal fees from Roche. No other disclosures were reported.

Figures

Figure 1. Meta-analysis of Odds Ratios for CKD Using Creatinine Values Comparing Sickle Cell Trait Carriers With Noncarriers

CKD indicates chronic kidney disease; eGFR, estimated glomerular filtration rate; SCT, sickle cell trait. Chronic kidney disease was defined as an eGFR level lower than 60 mL/min/1.73 m2 at baseline or follow-up. All models adjusted for age, sex, clinic or region, African genetic ancestry, hypertension, and diabetes. The size of data markers indicate the weight of study.

Figure 2. Meta-analysis of Odds Ratios for Incident CKD Using Creatinine Values Comparing Sickle Cell Trait Carriers With Noncarriers

CKD indicates chronic kidney disease; eGFR, estimated glomerular filtration rate; SCT, sickle cell trait. Incident CKD was defined as development of an eGFR level lower than 60 mL/min/1.73 m2 during follow-up. All models adjusted for age, sex, clinic or region, African genetic ancestry, hypertension, and diabetes. The size of data markers indicate the weight of study.

Figure 3. Meta-analysis of Odds Ratios for Estimated Glomerular Filtration Rate Decline Comparing Sickle Cell Trait Carriers With Noncarriers

CKD indicates chronic kidney disease; eGFR, estimated glomerular filtration rate; SCT, sickle cell trait. Estimated glomerular filtration rate decline was defined as a decrease in eGFR level of more than 3 mL/min/1.73 m2 per year. All models adjusted for age, sex, clinic or region, African genetic ancestry, hypertension, and diabetes. The size of data markers indicate the weight of study.

Figure 4. Meta-analysis of Odds Ratios for Albuminuria Comparing Sickle Cell Trait Carriers With Noncarriers

CKD indicates chronic kidney disease; SCT, sickle cell trait. Albuminuria was defined as spot urine albumin:creatinine ratio higher than 30 mg/g or albumin excretion rate higher than 30 mg/24 hours. All models adjusted for age, sex, clinic or region, African genetic ancestry, hypertension, and diabetes. The size of data markers indicate the weight of study.