November 13, 2014
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Sickle cell trait may increase risk for renal disease in blacks

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Black individuals who carried sickle cell trait demonstrated increased risk for chronic kidney disease and were more likely to experience declines in estimated glomerular filtration rate, according to study results.

They also were more likely to experience albuminuria, results showed.

Rakhi P. Naik, MD, a hematologist at Johns Hopkins University, and colleagues evaluated data from 15,975 adults enrolled on one of five prospective studies: the Atherosclerosis Risk in Communities Study; Jackson Heart Study; Coronary Artery Risk Development in Young Adults; Multi-Ethnic Study of Atherosclerosis; and the Women’s Health Initiative.

All patients were self-identified African Americans and had genotyping data available for rs334 encoding the sickle cell trait mutation.

Overall, 1,248 of the participants carried sickle cell trait, the prevalence of which ranged from 6.4% to 9.3% in the five study cohorts.

Researchers identified chronic kidney disease — defined as an estimated glomerular filtration rate (eGFR) ˂60 mL/min/1.73 m2 — in 2,233 of the study participants. A greater proportion of patients who carried sickle cell trait had chronic kidney disease (19.2% vs. 13.5%). Results of a meta-analysis indicated sickle cell trait carriers were at increased risk for chronic kidney disease (OR=1.57; 95% CI, 1.34-1.84).

The association between sickle cell trait carriage and chronic kidney disease persisted regardless of baseline hypertension (P=.09) or diabetes (P=.6), researchers wrote.

Researchers determined incident chronic kidney disease was more common in sickle cell trait carriers (20.7% vs. 13.7%), and results of a meta-analysis indicated sickle cell trait carriers were at increased risk for incident chronic kidney disease (OR=1.79; 95% CI, 1.45-2.2).

A greater proportion of sickle cell trait carriers experienced decline in eGFR (22.6% vs. 19%), defined as a yearly decrease of ˃3 mL/min/1.73 m2. Sickle cell trait carriers also were more likely to experience albuminuria (31.8% vs. 19.6%), which researchers measured based on a spot urinary albumin:creatinine ratio of ˃30 mg/g or by an albumin excretion rate ˃30 mg over 24 hours.

Multivariate analyses indicated sickle cell trait carriers were at increased risk for a decline in eGFR (OR=1.32; 95% CI, 1.07-1.61) and albuminuria (OR=1.86; 95% CI, 1.49-2.31).

Additional genetic analyses indicated APOL1 risk variants did not impact the associations between sickle cell trait and chronic kidney disease (P=.17) or albuminuria (P=.18).

“These associations … may offer an additional genetic explanation for the increased risk of chronic kidney disease observed among African Americans compared with other racial groups,” Naik said. “Our study also highlights the need for further research into the renal complications of sickle cell trait. Because screening for sickle cell trait is already being widely performed, accurate characterization of disease associations with sickle cell trait is critical to inform policy and treatment recommendations.”

Disclosure: The researchers report grant funding and personal fees from, as well as advisory board roles with, Amarin, AstraZeneca, Catabasis, Emmaus Life Sciences, GlycoMimetics, LabCorp, Merck, Novartis, Regeneron and Roche.