Abstract

Abstract Background and Aims Anemia is the most common finding in hemodialysis (HD) patients. A significant proportion of patients are taking erythropoietin (EPO) or other erythrocyte-stimulating agents (ESAs), yet the response to treatment is unsatisfactory, and EPO responsiveness is inconsistent in HD patients. Further, although the introduction of EPO has led to a dramatic reduction in blood transfusion requirements and is associated with improved quality of life, fluctuations in hemoglobin (Hb) levels, known as Hb variability, during EPO treatment is a well-documented phenomenon. Malnutrition is a well-known risk factor in the general population and in HD patients. However, few studies have evaluated the association between EPO responsiveness/Hb variability and nutritional status in HD patients. Therefore, our aim was to investigate whether EPO responsiveness and Hb variability can be associated with nutritional status in HD patients undergoing NESP® (darbepoetin-alfa; Kyowa Kirin Korea Co., Ltd.) treatment. Method In this prospective study, we included adult ninety-eight patients aged over 20 years who had been undergoing HD over 6 months. The target hemoglobin (Hb) level is 10–11 g/dL according to the Korean reimbursement guideline. Dose adjustments of NESP® were made according to the Hb level measured monthly in our facility. Every study population have more than 24 monthly Hb data points. We checked average darbepoetin-alfa dose weekly and the EPO resistance index (ERI) as a marker of EPO responsiveness was calculated by dividing the weekly average darbepoetin-alfa dose by the Hb level. In addition, we evaluated the more than 24 month Hb variability, which was expressed by Hb-Coefficient of Variation (Hb-CV). All of them were measured by BCM® (Fresenius Medical Care a Deutschland GmbH, Germany) to assess the nutritional status three times (Baseline, 12 Mos, 24 Mos). Nutritional parameters obtained by BCM® were body mass index (BMI), fat tissue index (FTI), lean tissue index (LTI), body cell mass index, phase angle (PhA). Clinical parameters and routine biochemical tests such as dose of erythropoietin, Kt/Vurea, iron and lipid profiles, C-reactive protein, albumin, calcium, phosphorus, intact-parathyroid hormone were also taken into account. Results In this study, the mean age of the patients was 64.0 ± 11.9 years, and 55.0% were male. Dialysis vintage was 54.9 ± 46.8 months. Follow-up duration was 79.3±47.9 months. Mean Hb was 10.7 ± 1.3 g/dL. We divided into tertiles (T) according to the ERI. The average ERI was 0.02 ± 0.01, 0.04 ± 0.01, and 0.07 ± 0.03 in ERI-T1, ERI-T2, and ERI-T3, respectively. The ERI-T3 group had the lower Hb level (p = 0.038) whereas administration dose of EPO were higher in ERI-T3 (p = 0.001). The ERI-T3 group had the lower PhA (p = 0.044), BMI (p = 0.001) and FTI (p = 0.046) values. We divided into tertiles (T) according to the Hb-CV. The average Hb-CV was 0.06 ± 0.01, 0.08 ± 0.05, and 0.12 ± 0.02 in Hb-CV-T1, Hb-CV-T2, and Hb-CV-T3, respectively. When comparing the three groups, the Hb-CV-T3 group had the lower BMI (p = 0.002) and lower FTI (p = 0.002). Age (r = 0.203, p = 0.036), female sex (r = 0.376, p = 0.001), presence of diabetes mellitus (r = 0.191, p = 0.049), total iron binding capacity (r = 0.205, p = 0.035) and triglyceride (r = 0.227, p = 0.018) were positively correlated with FTI. ERI (r = -0.193, p = 0.046) and Hb-CV (r = -0.268, p = 0.005) were negatively correlated with FTI. In multiple linear regression analysis, FTI was negatively associated with ERI (β = -0.218, p = 0.014), Hb-CV (β = -0.181, p = 0.039), whereas FTI was positively associated with age (β = 0.197, p = 0.017) and female sex (β = 0.386, p = 0.001). Conclusion In HD patients with higher ERI, PhA, BMI and FTI were significantly decreased. Furthermore, in patients with high Hb-CV, BMI and FTI were decreased. In addition, FTI was negatively associated with ERI and Hb-CV. Therefore, EPO responsiveness and Hb-variability is associated with nutritional status, especially fat tissue in hemodialysis patients undergoing darbepoetin-alfa treatment.

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