ORLANDO, Fla.—Variant hemoglobin phenotypes, including sickle cell trait and hemoglobin C trait, may be associated with resistance to treatment with erythropoiesis-stimulating agents (ESAs) among African Americans with end-stage renal disease (ESRD), according to researchers.

The study, led by Vimal K. Derebail, MD, of the University of North Carolina at Chapel Hill, included 155 African-American ESRD patients who underwent hemoglobin phenotyping. The researchers defined sickle cell trait as the presence of hemoglobin A and S (HbAS) and hemoglobin C trait as HbAC. They considered patients to be resistant to ESAs if their ESA dose was 6500 units per treatment or higher.

Of the 155 patients, 34 (21.9%) had variant hemoglobin, including 24 (15.4%) with HbAS, nine (5.8%) with HbAC, and one (0.64%) with beta-thalassemia trait, the investigators reported here at the National Kidney Foundation’s 2010 Spring Clinical Meetings. The median ESA doses per treatment for these patients were 4475.6, 7092, and 410.5 units, respectively. Among patients with normal hemoglobin, the median dose per treatment was 3684 units. Variant hemoglobin was associated with a three-fold increased odds of ESA resistance, after adjusting for multiple variables.

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Higher doses of ESA have been associated with increased cardiovascular morbidity and mortality so this link should be evaluated, especially in patients with variant hemoglobin, the researchers noted. In addition, both ESAs and sickle cell trait have been associated with venous thromboembolism, suggesting that high-dose ESA use in patients with sickle cell trait may have an augmented risk of thrombotic events, the researchers observed.

Study findings could have important consequences in light of the federal government’s proposed system of bundled payments for ESRD services. At present, Dr. Derebail’s group pointed out, bundled payments have no adjustments for race or hemoglobin phenotype, so African-American patients and centers that care for larger proportions of African Americans may be disadvantaged in the proposed system.