24‐hour Urinary Epinephrine and Interleukin‐6 are Independent Correlates of Endogenous Erythropoietin among Overweight Premenopausal Women

Abstract

PurposeAfrican American (AA) women frequently exhibit lower hemoglobin (Hb) and are less responsive to erythropoietin stimulating agents (ESAs) compared to European American (EA) women. These differences have led to the practice of AA receiving higher doses of ESAs compared to EA to achieve a similar level of improvement in Hb for treatment of anemia. However, higher doses of ESAs are associated with a greater risk of mortality. To date, it remains unclear whether differences in ESA responsiveness are due to race‐related differences in endogenous erythropoietin (EPO) production or other contributing factors. The objectives of the present work were two‐fold: 1) compare EPO between a cohort of AA and EA women and 2) identify potential physiological correlates of EPO using variables linked with ESA hyporesponsiveness.MethodsSecondary analyses were performed on 36 (AA; n = 14) overweight (28.3 ± 1.4 kg/m2), premenopausal women. Measurements were conducted following a 4‐week period wherein participants were held in energy balance (i.e., weight stable < 1% weekly fluctuation) via dietary control. Whole blood was collected after an overnight fast during the follicular phase of the menstrual cycle. Serum inflammatory biomarkers (interleukin‐6, tumor necrosis factor alpha) were measured in duplicate, while 24‐hour urinary fractionated catecholamines (epinephrine, norepinephrine, and dopamine) were measured with high‐performance liquid chromatography. Group allocation was based on self‐reported race. Non‐normally distributed data were log‐transformed. Between‐group comparisons were performed with independent t‐tests. Substantive differences were quantified using Hedges’ g. Following significant zero‐order correlations, a stepwise multiple linear regression was used to test the independent effects of variables on the variance in EPO.ResultsConsistent with previous work, AA had lower Hb (g·dL−1) (11.3 ± 0.7 vs. 12.6 ± 0.8 g·dL−1; p < 0.001; g = 1.67) and higher EPO (mIU·mL−1) (13.3 ± 6.8 vs. 8.0 ± 2.4; p = 0.014; g = 1.12). Significant between‐group differences were also observed for dopamine (p = 0.001) and total urinary catecholamines (p = 0.003). Among AA, Hb, interleukin‐6, and urinary epinephrine were significant correlates of EPO (all p < 0.05). Whereas only Hb correlated with EPO (p = 0.019) in EA. In the combined sample, regression modeling revealed Hb, interleukin‐6, and urinary epinephrine were significant correlates of EPO (R2 = 0.68; p < 0.001) independent of race. Of note, interleukin‐6 and urinary epinephrine respectively accounted for 17% and 19% of the variance in EPO.ConclusionsCompared with EA, AA women had higher EPO concentrations, however; other factors including systemic adrenergic activity and inflammation may explain these differences.Support or Funding InformationThis investigation was supported by the following grants from the National Institutes of Health: R25CA47888, R01AG027084‐01, R01AG027084‐S, P30DK056336, P60DK079626, and UL1RR025777.