title: The effect of cinacalcet on bone remodeling and renal function in transplant patients with persistent hyperparathyroidism.
abstract: BACKGROUND
  Parathyroidectomy is associated with renal functional losses in transplant patients; cinacalcet offers an attractive alternative.
  
  
  METHODS
  We performed a prospective observational study in 58 patients with persisting hyperparathyroidism after renal transplantation (Ca≥2.6 mmol/L) and impaired renal transplant function (estimated glomerular filtration rate [eGFR] <50 mL/min). The patients received 30 to 90 mg cinacalcet for 12 months with the target to normalize serum Ca. We measured parathyroid hormone (PTH), serum Ca, serum phosphorus, alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin, and telopeptide at 0, 1, 2, 3, 6, 9, and 12 months of cinacalcet treatment. Fractional excretion of calcium and phosphorus (n=24) were monitored at 0 and 1 month.
  
  
  RESULTS
  At inclusion, creatinine was 181±70 μmol/L, eGFR 43±19 mL/min, PTH 371±279 pg/mL, and Ca 2.73±0.22 mmol/L. We observed nephrocalcinosis in 58% of biopsied patients at enrollment. After cinacalcet, Ca decreased significantly and normalized at nearly any measurement. Phosphorus increased significantly at months 1, 9, and 12. PTH decreased significantly, but only at months 9 and 12 and did not normalize. Bone-specific alkaline phosphatase increased significantly (>normal) by month 12. eGFR decreased and serum creatinine increased at all time points. The Δ(creatinine) % increase correlated significantly with the Δ(PTH) % decrease at month 1 and 12. Telopeptide and alkaline phosphatase correlated with PTH and telopeptide also correlated with serum creatinine.
  
  
  CONCLUSIONS
  Calcium-phosphorus homeostasis in hypercalcemic renal transplant patients normalizes under cinacalcet and PTH decreases, albeit not to normal. The renal functional decline could be PTH mediated, analogous to the effects observed after parathyroidectomy.
authors.affiliation: Department of Nephrology, Hannover Medical School, Carl-Neuberg Strasse 1, Hannover, Germany. schwarz.anke@mh-hannover.de
authors.forename: Anke
authors.initials: A
authors.lastname: Schwarz
authors.forename: Saskia
authors.initials: S
authors.lastname: Merkel
authors.forename: Holger
authors.initials: H
authors.lastname: Leitolf
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
mesh_terms: D000368:Aged; D001706:Biopsy; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D000069449:Cinacalcet; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006961:Hyperparathyroidism / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000494:pharmacology* / Q000627:therapeutic use; D009397:Nephrocalcinosis / Q000378:metabolism / Q000473:pathology; D010281:Parathyroid Hormone / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism; D011446:Prospective Studies
chemical_list: D009281:Naphthalenes; D010281:Parathyroid Hormone; D010758:Phosphorus; D003404:Creatinine; D002118:Calcium; D000069449:Cinacalcet