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Sickle trait in African-American hemodialysis patients and higher erythropoiesis-stimulating agent dose.

ABSTRACT: African Americans require higher doses of erythropoiesis-stimulating agents (ESAs) during dialysis to manage anemia, but the influence of sickle cell trait and other hemoglobinopathy traits on anemia in dialysis patients has not been adequately evaluated. We performed a cross-sectional study of a large cohort of adult African-American hemodialysis patients in the United States to determine the prevalence of hemoglobinopathy traits and quantify their influence on ESA dosing. Laboratory and clinical data were obtained over 6 months in 2011. Among 5319 African-American patients, 542 (10.2%) patients had sickle cell trait, and 129 (2.4%) patients had hemoglobin C trait; no other hemoglobinopathy traits were present. Sickle cell trait was more common in this cohort than the general African-American population (10.2% versus 6.5%-8.7%, respectively, P<0.05). Among 5002 patients (10.3% sickle cell trait and 2.4% hemoglobin C trait) receiving ESAs, demographic and clinical variables were similar across groups, with achieved hemoglobin levels being nearly identical. Patients with hemoglobinopathy traits received higher median doses of ESA than patients with normal hemoglobin (4737.4 versus 4364.1 units/treatment, respectively, P=0.02). In multivariable analyses, hemoglobinopathy traits associated with 13.2% more ESA per treatment (P=0.001). Within subgroups, sickle cell trait patients received 13.2% (P=0.003) higher dose and hemoglobin C trait patients exhibited a similar difference (12.9%, P=0.12). Sensitivity analyses using weight-based dosing definitions and separate logistic regression models showed comparable associations. Our findings suggest that the presence of sickle cell trait and hemoglobin C trait may explain, at least in part, prior observations of greater ESA doses administered to African-American dialysis patients relative to Caucasian patients.

SUBMITTER: Derebail VK

PROVIDER: S-EPMC3968502 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Sickle trait in African-American hemodialysis patients and higher erythropoiesis-stimulating agent dose.

Derebail Vimal K VK Lacson Eduardo K EK Kshirsagar Abhijit V AV Key Nigel S NS Hogan Susan L SL Hakim Raymond M RM Mooney Ann A Jani Chinu M CM Johnson Curtis C Hu Yichun Y Falk Ronald J RJ Lazarus J Michael JM

Journal of the American Society of Nephrology : JASN 20140123 4

African Americans require higher doses of erythropoiesis-stimulating agents (ESAs) during dialysis to manage anemia, but the influence of sickle cell trait and other hemoglobinopathy traits on anemia in dialysis patients has not been adequately evaluated. We performed a cross-sectional study of a large cohort of adult African-American hemodialysis patients in the United States to determine the prevalence of hemoglobinopathy traits and quantify their influence on ESA dosing. Laboratory and clinic ...[more]

PMID: 24459231

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Project description:The increased risks of death and adverse events with erythropoiesis-stimulating agent (ESA) therapy targeting a higher hemoglobin level are established. It is uncertain whether the adverse effects of ESA therapy are related to dose and are mitigated when a fixed low ESA dose is used. We conducted a multicenter, prospective randomized open-label, blinded-endpoint (PROBE) trial to evaluate fixed low versus high dose ESA therapy on patient outcomes. We intended to recruit 2104 hemodialysis patients >18 years with anemia or receiving ESA treated at dialysis clinics in Italy. The intervention was fixed low (4000 IU epoetin alfa equivalent weekly) or high (18,000 IU epoetin alfa equivalent weekly) dose ESA for 12 months. Primary outcomes were serum transferrin, ferritin, albumin, C-reactive protein and ESA dose. Secondary outcomes were the composite of death or cardiovascular event, all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, cardiovascular hospitalization, and quality of life. Study recruitment was terminated after inclusion of 656 participants with convergence of ESA dose between groups during follow up. Fixed low dose ESA had uncertain effects on serum ferritin (delta of delta (DD) 3.9 ng/ml, 95% CI -85.0 to 92.8), transferrin (9.2 mg/dl, -6.3 to 24.8), transferrin saturation (3.7%, -5.0 to 12.3), serum albumin (-0.03 g/dl, -0.2 to 0.1), or C-reactive protein (-0.6 mg/l, -3.3 to 2.1). In addition, fixed dose therapy had inconclusive effects on the composite endpoint of mortality and cardiovascular events (hazard ratio [HR] 0.95, 95% CI 0.66 to 1.37), death (0.98, 0.64 to 1.52), nonfatal myocardial infarction (0.52, 0.18 to 1.52), nonfatal stroke (no events), hospital admission for cardiovascular causes (0.93, 0.50 to 1.72) or health-related quality of life. A fixed low ESA dose in hemodialysis patients has uncertain effects on serum parameters, mortality, cardiovascular events, and quality of life. Hemoglobin targets may be so entrenched in nephrology practice that a trial of ESA dose is no longer possible.

Project description:Observational studies indicate greater survival in African American and Hispanic maintenance hemodialysis patients compared with their non-Hispanic white counterparts, although African Americans have shorter life expectancy than whites in the general population. We hypothesized that this apparent survival advantage is due to a more favorable nutritional/inflammatory profile in minority hemodialysis patients.We examined the association between race/ethnicity and 5-year survival before and after adjustment for case-mix and surrogates of the malnutrition-inflammation complex syndrome (MICS) using Cox regression with or without matched sampling in a large cohort of adult hemodialysis patients.124,029 adult hemodialysis patients, including 16% Hispanics, 49% non-Hispanic whites, and 35% African Americans.Race/ethnicity before and after adjustment for MICS, including values for body mass index, serum albumin, total iron-binding capacity, ferritin, creatinine, phosphorus, calcium, bicarbonate, white blood cell count, lymphocyte percentage, hemoglobin, and protein intake.5-year (July 2001 to June 2006) survival.In dialysis patients, blacks and Hispanics had lower mortality overall than non-Hispanic whites after traditional case-mix adjustment. However, after additional control for MICS, Hispanics had mortality similar to non-Hispanic whites, and African Americans had even higher mortality. Unadjusted, case-mix-, and MICS-adjusted HRs for African Americans versus whites were 0.68 (95% CI, 0.66-0.69), 0.89 (95% CI, 0.86-0.91), and 1.06 (95% CI, 1.03-1.09) in the unmatched cohort and, 0.95 (95% CI, 0.90-0.99), 0.89 (95% CI, 0.84-0.94), and 1.16 (95% CI, 1.07-1.26) in the matched cohort, and for Hispanics versus whites, 0.66 (95% CI, 0.64-0.69), 0.84 (95% CI, 0.81-0.87), and 0.97 (95% CI, 0.94-1.00) in the unmatched cohort and 0.89 (95% CI, 0.84-0.95), 0.88 (95% CI, 0.83-0.95), and 0.98 (95% CI, 0.91-1.06) in the matched cohort, respectively.Adjustment cannot be made for unmeasured confounders.Survival advantages of African American and Hispanic hemodialysis patients may be related to differences in nutritional and inflammatory status. Further studies are required to explore these differences.

Dataset Information

Sickle trait in African-American hemodialysis patients and higher erythropoiesis-stimulating agent dose.

Publications

Sickle trait in African-American hemodialysis patients and higher erythropoiesis-stimulating agent dose.

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