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Sickle Cell Trait Linked to Chronic Kidney Disease Risk

By LabMedica International staff writers
Posted on 30 Nov 2014
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Image: The BN II protein analyzer system (Photo courtesy of Siemens).
Image: The BN II protein analyzer system (Photo courtesy of Siemens).
Sickle cell trait (SCT) is defined as inheritance of a single copy of the sickle mutation that results from a single base pair substitution in the gene encoding the β-globin chain of hemoglobin.

Although SCT largely has been considered a benign condition, renal manifestations are the most commonly reported complications and include impaired urinary concentration, asymptomatic hematuria, and papillary necrosis and it is estimated that SCT affects nearly 300 million people worldwide.

Scientists at Johns Hopkins University (Baltimore, MD, USA) and their colleagues from several other institutions used five large, prospective, US population-based studies to evaluate 15, 975 self-identified African Americans, 1,248 participants who were SCT carriers and 14,727 participants without SCT, the noncarriers. Genotype data for rs334 encoding the sickle cell mutation (HBB p.Glu7Val) were obtained by custom genotyping or exome sequencing, or by imputation into the remaining sample of African Americans with genome-wide genotyping.

Allele detection and genotype calling were performed using the ABI 7900HT and the Sequence Detection System software (Life Technologies, Grand Island, NY, USA; www.lifetechnologies.com). They examined kidney function outcomes by the number of risk alleles. Serum creatinine values were measured via a modified kinetic Jaffé method or isotope dilution mass spectrometry. Cystatin C was measured using the Siemens Healthcare Diagnostics BN II System (Malvern, PA, USA) by an immunonephelometric assay.

The team identified chronic kidney disease (CKD) among 2,233 participants and of these, 19.2% of cases occurred among individuals with SCT, while 13.5% of cases were among those without the condition. The rate of incident CKD was also higher among individuals with SCT than those without the condition, at 20.7% and 13.7%, respectively. The team also found that people with SCT had a faster decline in estimated glomerular filtration rate (eGFR), the rate at which fluid is filtered through the kidney; 22.6% of those with sickle cell trait experienced eGFR decline, compared with 19% of those without the condition. What is more, 31.8% of people with SCT experienced albuminuria, an excess of protein in the urine that can be a sign of a kidney disorder, compared with 19% of those free of SCT.

The authors concluded that in their large multicohort study, SCT was associated with CKD and incident CKD, decline in eGFR, and albuminuria in African Americans. Because screening for SCT is already being widely performed, accurate characterization of disease associations with SCT is critical to inform policy and treatment recommendations. These associations may offer an additional genetic explanation for the increased risk of CKD observed among African Americans, compared with other racial groups. The study was published on November 13, 2014, in the Journal of the American Medical Association.

Related Links:

Johns Hopkins University 
Life Technologies
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