Combined therapy with cinacalcet and low doses of vitamin D sterols in patients with moderate to severe secondary hyperparathyroidism

Nephrol Dial Transplant. 2008 Jul;23(7):2311-8. doi: 10.1093/ndt/gfn026. Epub 2008 Feb 29.

Abstract

Background: Adequate control of all four KDOQI biochemical targets for chronic kidney disease, bone and mineral disorder (CKD-MBD), which include parathyroid hormone (PTH), calcium (Ca), phosphorus (P) and Ca x P, remains difficult and is accomplished in <6% of patients receiving haemodialysis. The objective of the current study was to determine whether treatment with cinacalcet combined with low doses of vitamin D sterols improves control of both PTH and Ca x P among haemodialysis patients with secondary hyperparathyroidism (sHPT).

Methods: This multicentre, open-label study enrolled haemodialysis subjects (N = 444) with moderate to severe sHPT (mean serum biPTH > 160-430 pg/mL) (approximately iPTH 300-800 pg/mL or ng/L). Cinacalcet was titrated sequentially (30-180 mg/day) during an 8-week dose-titration phase to achieve biPTH <or=160 pg/mL (approximately iPTH 300 pg/mL or ng/L) and efficacy was assessed over 8 weeks. At week 2 of the study, subjects receiving vitamin D sterols had doses reduced to the equivalent of 2 mcg of paricalcitol three times a week or 6 mcg/week. Among the efficacy endpoints were the proportion of subjects with mean biPTH <or=160 pg/mL (approximately iPTH 300 pg/mL or ng/L), with mean Ca x P <or=55 mg(2)/dL(2) (4.4 mmol(2)/L(2)) and with both simultaneously during the assessment phase.

Results: The majority of subjects (n = 375) reached the assessment phase of the study and were included in efficacy analyses; 39 subjects withdrew due to adverse events. Sixty-two percent of subjects achieved the biPTH target, 83% achieved the Ca x P target and 54% reached both targets. Treatment reduced biPTH by 35% (P < 0.0001), calcium by 11% (P < 0.0001), phosphorus by 7% (P < 0.0001) and Ca x P by 17% (P < 0.0001). The proportion of subjects with values for biPTH, for Ca x P and for both biPTH and Ca x P within the target range during the assessment phase did not differ between subjects who received cinacalcet together with vitamin D sterols, and those who received cinacalcet alone.

Conclusion: Among subjects with moderate to severe sHPT undergoing haemodialysis, combined therapy with cinacalcet and low doses of vitamin D sterols improved achievement of the biochemical targets for CKD-MBD recommended by the KDOQI guidelines.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Calcium / blood
  • Cinacalcet
  • Dose-Response Relationship, Drug
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypercalcemia / blood
  • Hypercalcemia / prevention & control
  • Hyperparathyroidism, Secondary / blood
  • Hyperparathyroidism, Secondary / drug therapy*
  • Hyperphosphatemia / blood
  • Hyperphosphatemia / prevention & control
  • Male
  • Middle Aged
  • Naphthalenes / therapeutic use*
  • Parathyroid Hormone / blood
  • Phosphorus / blood
  • Severity of Illness Index
  • Sterols / therapeutic use*
  • Treatment Outcome
  • Vitamin D / therapeutic use*

Substances

  • Naphthalenes
  • Parathyroid Hormone
  • Sterols
  • Vitamin D
  • Phosphorus
  • Calcium
  • Cinacalcet