title: Predictors of hyporesponsiveness to erythropoiesis-stimulating agents in hemodialysis patients.
abstract: BACKGROUND
  Identification of predictors of hyporesponsiveness to erythropoietin-stimulating agents (ESAs) in hemodialysis (HD) patients may help improve anemia management and reduce hemoglobin level variability.
  
  
  METHODS
  We conducted repeated-measure and logistic regression analyses in a retrospective cohort of long-term HD patients to examine the association of iron markers and measures of renal osteodystrophy with ESA responsiveness. The ESA response coefficient at the individual level, ie, the least confounded dose-response association, was separated from the population level, assumed to represent confounding by medical indication.
  
  
  METHODS
  The national database of a large dialysis organization (DaVita Inc, El Segundo, CA) with 38,328 surviving prevalent HD patients during 12 months who received ESA for at least 3 consecutive calendar quarters was examined.
  
  
  METHODS
  Serum levels of ferritin, iron saturation ratio, intact parathyroid hormone, and alkaline phosphatase. OUTCOMES/OTHER MEASUREMENTS: The main outcome was case-mix-adjusted hemoglobin response to quarterly averaged ESA dose at the individual level. The odds ratio (OR) of the greatest versus poorest ESA-response quartile at the patient level was calculated. OR less than 1.0 indicated ESA hyporesponsiveness, and OR greater than 1.0, enhanced responsiveness.
  
  
  RESULTS
  Mean ESA-response coefficients of the least to most responsive quartiles were 0.301 +/- 0.033 (SD), 0.344 +/- 0.004, 0.357 +/- 0.004, and 0.389 +/- 0.026 g/dL greater hemoglobin level per 1,000 U/wk greater ESA dose in each quarter, respectively. The ORs of greatest versus poorest ESA responsiveness at the patient level were serum ferritin level less than 200 ng/mL (0.77; 95% confidence interval [CI], 0.70 to 0.86; reference, 200 to 500 ng/mL), iron saturation ratio less than 20% (0.54; 95% CI, 0.49 to 0.59; reference, 20% to 30%), intact parathyroid hormone level of 600 pg/mL or greater (0.54; 95% CI, 0.49 to 0.60; reference, 150 to 300 pg/mL), and alkaline phosphatase level of 160 IU/L or greater (0.64; 95% CI, 0.58 to 0.70; reference, 80 to 120 IU/L). Lower estimated dietary protein intake and serum levels of nutritional markers were also associated with greater risk of ESA hyporesponsiveness.
  
  
  CONCLUSIONS
  Our results may incorporate uncontrolled confounding. Achieved hemoglobin level may have different associations than targeted hemoglobin level.
  
  
  CONCLUSIONS
  In long-term HD patients, low iron stores, hyperparathyroidism, and high-turnover bone disease are associated with significant ESA hyporesponsiveness. Prospective studies are needed to verify these associations.
authors.affiliation: Harold Simmons Center for Kidney Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90509-2910, USA. kamkal@ucla.edu
authors.forename: Kamyar
authors.initials: K
authors.lastname: Kalantar-Zadeh
authors.forename: Grace H
authors.initials: GH
authors.lastname: Lee
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Miller
authors.forename: Elani
authors.initials: E
authors.lastname: Streja
authors.forename: Jennie
authors.initials: J
authors.lastname: Jing
authors.forename: John A
authors.initials: JA
authors.lastname: Robertson
authors.forename: Csaba P
authors.initials: CP
authors.lastname: Kovesdy