title: Association between high-dose erythropoiesis-stimulating agents, inflammatory biomarkers, and soluble erythropoietin receptors.
abstract: BACKGROUND
  High-dose erythropoiesis-stimulating agents (ESA) for anemia of chronic kidney disease (CKD) have been associated with adverse clinical outcomes and do not always improve erythropoiesis. We hypothesized that high-dose ESA requirement would be associated with elevated inflammatory biomarkers, decreased adipokines, and increased circulating, endogenous soluble erythropoietin receptors (sEpoR).
  
  
  METHODS
  A cross-sectional cohort of anemic 32 CKD participants receiving ESA were enrolled at a single center and cytokine profiles, adipokines, and sEpoR were compared between participants stratified by ESA dose requirement (usual-dose darbepoetin-α (< 1 μg/kg/week) and high-dose (≥ 1 μg/kg/week)).
  
  
  RESULTS
  Baseline characteristics were similar between groups; however, hemoglobin was lower among participants on high-dose (1.4 μg/kg/week) vs usual-dose (0.5 μg/kg/week) ESA.In adjusted analyses, high-dose ESA was associated with an increased odds for elevations in c-reactive protein and interleukin-6 (p < 0.05 for both). There was no correlation between high-dose ESA and adipokines. Higher ESA dose correlated with higher levels of sEpoR (rs = 0.39, p = 0.03). In adjusted analyses, higher ESA dose (per μcg/kg/week) was associated with a 53% greater odds of sEpoR being above the median (p < 0.05).
  
  
  CONCLUSIONS
  High-dose ESA requirement among anemic CKD participants was associated with elevated inflammatory biomarkers and higher levels of circulating sEpoR, an inhibitor of erythropoiesis. Further research confirming these findings is warranted.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT00526747.
authors.affiliation: Department of Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390-8523, USA. jula.inrig@utsouthwestern.edu
authors.forename: Jula K
authors.initials: JK
authors.lastname: Inrig
authors.forename: Suzanne K
authors.initials: SK
authors.lastname: Bryskin
authors.forename: Uptal D
authors.initials: UD
authors.lastname: Patel
authors.forename: Murat
authors.initials: M
authors.lastname: Arcasoy
authors.forename: Lynda A
authors.initials: LA
authors.lastname: Szczech
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006397:Hematinics / Q000008:administration & dosage*; D006801:Humans; D007155:Immunologic Factors / Q000097:blood; D007249:Inflammation / Q000097:blood / Q000276:immunology* / Q000517:prevention & control*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D008297:Male; D017467:Receptors, Erythropoietin / Q000276:immunology*; D012995:Solubility; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D006397:Hematinics; D007155:Immunologic Factors; D017467:Receptors, Erythropoietin