title: 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.
authors.affiliation: Department of Internal Medicine, Uijeongbu St. Mary's Hospital, Kyonggi-do, Korea.
authors.forename: Hye Sung
authors.initials: HS
authors.lastname: Won
authors.forename: Hyun Gyung
authors.initials: HG
authors.lastname: Kim
authors.forename: Yu Seon
authors.initials: YS
authors.lastname: Yun
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Jeon
authors.forename: Yoon Ho
authors.initials: YH
authors.lastname: Ko
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Young Ok
authors.initials: YO
authors.lastname: Kim
authors.forename: Sun Ae
authors.initials: SA
authors.lastname: Yoon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000188:drug therapy*; D023181:Antimicrobial Cationic Peptides / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003430:Cross-Sectional Studies; D004351:Drug Resistance; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D064451:Hepcidins; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D000090463:Iron Deficiencies; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects*; D012307:Risk Factors
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D006397:Hematinics; D064451:Hepcidins; C508600:IL6 protein, human; D015850:Interleukin-6; D002097:C-Reactive Protein