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


CONCLUSIONS
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.
Block
Geoffrey A
GA
Denver Nephrologists, Denver, CO 80230, USA. gablock@denverneph.net
Zeig
Steven
S
Sugihara
Jared
J
Chertow
Glenn M
GM
Chi
Eric M
EM
Turner
Stewart A
SA
Bushinsky
David A
DA
D000328:Adult; D000368:Aged; D002118:Calcium / Q000097:blood; D000069449:Cinacalcet; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000517:prevention & control; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy*; D054559:Hyperphosphatemia / Q000097:blood / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D012720:Severity of Illness Index; D013261:Sterols / Q000627:therapeutic use*; D016896:Treatment Outcome; D014807:Vitamin D / Q000627:therapeutic use*
D009281:Naphthalenes; D010281:Parathyroid Hormone; D013261:Sterols; D014807:Vitamin D; D010758:Phosphorus; D002118:Calcium; D000069449:Cinacalcet