Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients.
BACKGROUND
Calcimimetic agents have recently been evaluated in the treatment of secondary hyperparathyroidism (SHPT) as add-on therapy to calcitriol and vitamin D analogues and dietary phosphate binders.


OBJECTIVE
To evaluate the benefits and harms of calcimimetics for the prevention of secondary hyperparathyroid bone disease (including osteitis fibrosa cystica and adynamic bone disease) in dialysis patients with chronic kidney disease (CKD).


METHODS
MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and conference proceedings were searched for randomised controlled trials (RCTs) evaluating any calcimimetic against placebo or another agent in pre-dialysis or dialysis patients with CKD.


METHODS
We included all RCTs of any calcimimetic agent, cinacalcet HCl (AMG-073, Sensipar), NPS R-467 or NPS R-568 administered to patients with CKD for the treatment of SHPT.


METHODS
Data were extracted on all relevant patient-centred and surrogate outcomes. Analysis was by a random effects model and results expressed as relative risk (RR) or weighted mean difference (MD) with 95% confidence intervals.


RESULTS
Eight studies (1429 patients) were identified, which compared a calcimimetic agent plus standard therapy to placebo plus standard therapy. The end of treatment values of parathyroid hormone (pg/mL) (MD -290.79, 95% CI -360.23 to -221.34), serum calcium (mg/dL) (MD -0.85, 95% CI -1.14 to -0.56), serum phosphorus (mg/dL) (MD -0.29, 95% CI -0.50 to -0.08) and the calcium by phosphorus product (mg(2)/dL(2))(MD -7.90, 95% CI -10.25 to -5.54) were significantly lower with calcimimetics compared to placebo. No significant effects on patient-based endpoints were demonstrated except for the risk of hypotension which was significantly reduced with calcimimetics compared to placebo (RR 0.53, 95%CI 0.36 to 0.79).


CONCLUSIONS
Calcimimetic treatment of SHPT leads to significant improvements in biochemical parameters that observational studies have shown to be associated with increased mortality, cardiovascular risk and osteitis fibrosa, but patient-based benefits have not yet been demonstrated in trials. For patients with SHPT, the benefits of calcimimetics over standard therapy remain uncertain until further RCTs become available.
Strippoli
G F M
GF
NHMRC Centre for Clinical Research Excellence in Renal Medicine, Cochrane Renal Group, Centre for Kidney Research, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, NSW, Australia. gfmstrippoli@alice.it
Tong
A
A
Palmer
S C
SC
Elder
G
G
Craig
J C
JC
D002118:Calcium / Q000819:agonists* / Q000097:blood; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000628:therapy; D010281:Parathyroid Hormone / Q000097:blood; D010758:Phosphorus / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis
C470125:PTH protein, human; D010281:Parathyroid Hormone; D010758:Phosphorus; D002118:Calcium