Anemia is a common complication in dialysis patients because of their relative erythropoietin deficiency. Despite treatment with erythropoiesis-stimulating agents (ESAs), some patients experienced ESA hyporesponsiveness. We evaluated the clinical and laboratory factors that affect ESA hyporesponsiveness and investigated the relationships between hepcidin, inflammatory markers, and the iron profiles of hemodialysis patients. Sixty-eight patients receiving hemodialysis at a single institution were evaluated in a cross-sectional study. The patients were divided into tertiles based on the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram of body weight divided by the hemoglobin level. The mean EHRI values for each tertile were 3.3 ± 1.2 (T1), 10.2 ± 2.9 (T2), and 24.5 ± 11.6 (T3). The mean serum erythropoietin levels were significantly higher in the Q3 and Q4 groups. Thus, patients with ESA hyporesponsiveness showed relative resistance to erythropoietin therapy. In univariate and multivariate analyses, patients in the third tertile of EHRI showed significantly higher mean interleukin-6 (IL-6) levels. Serum C-reactive protein (CRP) levels showed a similar trend, but the differences were not significant. Serum hepcidin levels tended toward lower mean values in the third tertile of EHRI. No relationship was observed between hepcidin and inflammatory markers or iron status. In conclusion, IL-6, but not CRP, is a strong predictor of ESA hyporesponsiveness in hemodialysis patients who have sufficient iron. It may be difficult to use hepcidin as an independent clinical marker because of the many factors that influence it and their interactions.

Gross vascular calcification seen on imaging studies is common in hemodialysis (HD) patients, and is a significant predictor for cardiovascular mortality in HD patients. We have reported that arterial microcalcification (AMiC) of the vascular access is associated with increased aortic stiffness. This study investigated the impact of vascular access AMiC on cardiovascular mortality in HD patients. The study included 149 HD patients (mean age: 59.1 ± 13.9 years, 86 men and 63 women, 65.8% diabetic) who underwent vascular access surgery. Radial or brachial artery specimens were obtained intraoperatively, and pathologic examination was performed using von Kossa stain to identify AMiC. We compared all-cause and cardiovascular mortality between patients with and without AMiC. The mean follow-up was 37.8 ± 34.5 months, and AMiC was present in 38.8% (n = 57) of patients. The presence of diabetes (odds ratio: 16.49, 95% confidence interval: 1.81-150.36, P = 0.013) was the only independent risk factor for vascular access AMiC. During the observational period, there were 27 cardiovascular deaths. Kaplan-Meier analysis showed an increased cardiovascular mortality risk (log rank = 4.83, P = 0.028) in AMiC patients, and Cox regression analysis confirmed that AMiC was an independent predictor for cardiovascular mortality (hazard ratio: 2.35, 95% confidence interval: 1.09-5.09, P = 0.030). In conclusion, vascular access AMiC is a strong risk factor for cardiovascular mortality in HD patients.

The aim of this study was to evaluate the relationship between arterial microcalcification (AMiC) and erythropoiesis-stimulating agents (ESA) hyporesponsiveness in hemodialysis patients. The presence of AMiC was confirmed by pathologic examination of von Kossa-stained arterial specimens acquired during vascular access surgery. We assessed the ESA hyporesponsiveness index (EHRI), defined as the weekly ESA dose per kilogram body weight divided by the hemoglobin level. AMiC was detected in 33 (40.2%) of 82 patients. Patients with diabetes had a higher incidence of AMiC than patients without diabetes. The serum levels of albumin and cholesterol were higher in patients without AMiC than in patients with AMiC. The serum levels of intact parathyroid hormone were lower in patients with AMiC than in patients without AMiC. The serum levels of phosphate and calcium-phosphorus product did not differ between the two groups. The mean EHRI value was higher in patients with AMiC than in patients without AMiC. In multivariate analyses, ESA hyporesponsiveness and diabetes showed a significant association with AMiC. In conclusion, ESA hyporesponsiveness may be a clinical relevant parameters related to AMiC in hemodialysis patients.

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