title: Improved parathyroid hormone control by cinacalcet is associated with reduction in darbepoetin requirement in patients with end-stage renal disease.
abstract: BACKGROUND
  Uncontrolled hy-per-parathyroidism causes bone marrow fibrosis, leading to erythropoietin (EPO) resistance. Medical treatment with cinacalcet is effective in reducing plasma parathyroid hormone (PTH) levels, but its effect on darbepoetin dosing is unknown.
  
  
  OBJECTIVE
  We conducted a retrospective cohort study of 40 end-stage renal disease (ESRD) patients (age: 55 ± 14; mean ± SD; 21:male) who had at least 12 months of cinacalcet therapy. The distribution of renal replacement therapies were: 14 peritoneal dialysis, 18 conventional hemodialysis and 8 nocturnal hemodialysis. Standard dialysis related biochemical indices and medications used were recorded. The primary objective of the study was to ascertain the difference in darbepoetin responsiveness before and after 12 months of cinacalcet therapy. Our secondary objective was to determine if there was a relationship between the changes in PTH and darbepoetin requirement.
  
  
  RESULTS
  Overall, PTH levels decreased from 197.5 (151.8; 249.2) to 66.1 (41.2; 136.5) (median (25th;75th percentile)) pmol/l; p < 0.001. Cinacalcet dose increased from 30.0 ± 6 to 63 ± 25 mg/day, p < 0.05. Hemoglobin remained unchanged (116 ± 13 to 116 ± 13 g/l), while darbepoetin requirement decreased from 40 (20; 60) to 24 (19; 59) μg/week, p = 0.02. The remainder of the dialysis-related biochemistry (electrolytes, calcium, phosphate, iron status) and vitamin D use remained unchanged. A reduction in PTH level of greater than 30% was experienced by 82.5% (33/40) of our cohort. Among the responders, the fall in PTH and reduction darbepoetin requirement were related (R = -0.48, p = 0.004).
  
  
  CONCLUSIONS
  Reduction of PTH by cinacalcet is associated with a decrease in darbepoetin requirement. The interface between bone and bone marrow in uremia represents a critical step in red blood cell production which merits further investigation.
authors.affiliation: Division of Nephrology, Department of Medicine, University Health Network, Toronto, ON, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Battistella
authors.forename: R M A
authors.initials: RM
authors.lastname: Richardson
authors.forename: J M
authors.initials: JM
authors.lastname: Bargman
authors.forename: C T
authors.initials: CT
authors.lastname: Chan
mesh_terms: D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D000069449:Cinacalcet; D015331:Cohort Studies; D000068256:Darbepoetin alfa; D004347:Drug Interactions; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006397:Hematinics / Q000008:administration & dosage*; D006801:Humans; D006961:Hyperparathyroidism / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000378:metabolism*; D006435:Renal Dialysis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D006397:Hematinics; D009281:Naphthalenes; D010281:Parathyroid Hormone; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000069449:Cinacalcet