IL‐6 is an independent risk factor for resistance to erythropoiesis‐stimulating agents in hemodialysis patients without iron deficiency

Abstract

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.

Pre-Emptive Replacement of Water Treatment Components Improves Responsiveness to Erythropoiesis-Stimulating Agents in Maintenance Haemodialysis Patients: A Quality Improvement Report

“…We did not observe a change in high-sensitivity CRP measurements in our cohort following intervention, but cannot exclude the possibility that improvement in ESA responsiveness was mediated by reduction in low levels of inflammation, which were not detectable by this assay. This is in keeping with data demonstrating improved ESA responsiveness with lower IL-6 levels but without an accompanying significant rise in CRP [38]. …”

C-reactive protein but not hepcidin, NGAL and transferrin determines the ESA resistance in hemodialysis patients

“…Malyszko et al found a positive correlation between hepcidin and CRP levels, whereas others did not. [17][18][19][20][21] In the study by Caliskan et al, 20 serum prohepcidin levels were found to be significantly associated with serum IL-6 levels, however, no significant association was found between prohepcidin and CRP in HD patients. In addition, in our study, serum hepcidin levels were not related to serum CRP levels.…”

Correlation between Inflammatory Biomarkers and Red Blood Cell Life Span in Chronic Hemodialysis Patients

“…HD patients present frequently with high levels of inflammatory markers such as high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, tumor necrosis factor-α, neutrophil-to-lymphocyte ratio (NLR) [7], and low levels of serum albumin [8]. Increased levels of pro-inflammatory cytokines reduce the production of erythroid progenitor cells and this contributes to hyporesponsiveness to ESAs and poor treatment outcomes [9,10]. Elevated levels of inflammatory cytokines also contribute to functional iron deficiency.…”