Abstract

Growth arrest-specific protein 6 (Gas6) works synergistically with erythropoietin (EPO) to increase the proliferation and maturation of erythroblasts. However, the role of Gas 6 levels on EPO resistance in hemodialysis (HD) patients remains unclear. Therefore, the objective of this study was the first to examine the correlation between plasma Gas6 levels and EPO resistance in HD patients. We enrolled 134 HD patients and 85 healthy individuals. The HD patients were divided into 2 groups: 98 non-EPO-resistant patients and 36 EPO-resistant patients. Plasma levels of Gas6, interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and albumin were quantified. Compared with non-EPO-resistant patients, EPO-resistant patients had elevated plasma concentrations of Gas6 (15.4 ± 3.3 vs. 13.7 ± 3.2 ng/mL, P = 0.006), IL-6 (3.1 ± 3.1 vs. 2.1 ± 1.5 pg/mL, P = 0.009), and hs-CRP (12.7 ± 25.2 vs. 4.5 ± 5.5 mg/L, P = 0.002). In EPO-resistant HD patients, plasma Gas6 levels were negatively correlated with albumin levels (r = −0.388, P < 0.021). Elevated Gas6 levels are associated with EPO resistance in HD patients. Also, EPO resistance is related to inflammation and malnutrition. Thus, circulating Gas6 levels could be used as the potential marker in HD patients with EPO resistance.

Highlights

  • Erythropoietin (EPO) resistance is one of the most common complications in anemia patients undergoing hemodialysis (HD)

  • Our results showed that elevated circulating Growth arrest-specific protein 6 (Gas6) levels were associated with EPO resistance in HD patients

  • Gas6 growth arrest-specific 6, EPO erythropoietin, SI serum iron, transferrin saturation (TSAT) transferring saturation, TIBC total iron-binding capacity, i-PTH intact parathyroid hormone, Hct hematocrit, interleukin 6 (IL-6) Interleukin 6, Hs-CRP high sensitivity C-reactive protein, EPO erythropoietin were negatively correlated with albumin levels in EPOresistant HD patients

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Summary

Introduction

Erythropoietin (EPO) resistance is one of the most common complications in anemia patients undergoing hemodialysis (HD). Most factors causing EPO resistance are associated with malnutrition, chronic inflammation, hyperparathyroidism, and inadequate dialysis in HD patients, which shorten the lifespan of erythrocytes (Macdougall and Cooper 2002; Kanbay et al 2010). A careful evaluation of EPO resistance is crucial in patient care for improving clinical outcomes. It was recently reported that elevated circulating Gas levels are correlated with disease activity such as systemic inflammation (Ekman et al 2010a, b), acute coronary syndrome (Jiang et al 2009), acute pancreatitis (Uehara et al 2009), and systemic lupus erythematosus (Ekman et al 2011). In patients with critical limb ischemia, circulating Gas levels correlated with survival outcomes, indicating that Gas can be considered as a potential biomarker in clinical practice (Ekman et al 2010a, b)

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