title: Cinacalcet versus standard treatment for chronic kidney disease: a systematic review and meta-analysis.
abstract: BACKGROUND
  Chronic kidney disease-mineral and bone disorders (CKD-MBD) have been associated with poor health outcomes, including diminished quality and length of life. Standard management for CKD-MBD includes phosphate restricted diet, vitamin D and phosphate binders. Persistently elevated parathyroid hormone levels may require the addition of cinacalcet hydrochloride (cinacalcet), which sensitizes calcium receptors in the parathyroid gland.
  
  
  OBJECTIVE
  The objective of this systematic review is to compare, in patients with CKD-MBD the effect of cinacalcet versus standard treatment on patient-important outcomes, including parathyroidectomy, fractures, hospitalizations due to cardiovascular events, cardiovascular mortality, all-cause mortality, and intermediate outcomes, in particular Kidney Disease Outcome Quality Initiative targets.
  
  
  METHODS
  Data sources included MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and Web of Science from 1996 to June 2015. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible trials. We calculated the effect estimates (risk ratios or mean differences) and 95% confidence intervals, as well as statistical measures of variability in results across studies using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate quality of evidence about estimates of effect on an outcome-by-outcome basis for all outcomes. We presented our results with a GRADE summary table.
  
  
  RESULTS
  Twenty-four trials including 8311 CKD patients proved eligible. The results left considerable uncertainty regarding the impact of cinacalcet on reducing fractures (relative risk [RR] 0.59, 95% confidence interval [CI] 0.13-2.60; heterogeneity: p = 0.03, I(2)= 78%; very low quality evidence), and indicated that cinacalcet did not reduce hospitalizations due to cardiovascular events (RR 0.93, 95% CI 0.85-1.02, moderate quality of evidence), cardiovascular mortality (RR 0.95, 95% CI 0.84-1.07; heterogeneity p= 0.61, high quality evidence) or all-cause mortality (RR 0.96, 95% CI 0.89-1.04; heterogeneity: p= 0.98, I(2)= 0%; moderate quality evidence). Cinacalcet reduced the need for parathyroidectomy (RR 0.30, 95% CI 0.22-0.42; heterogeneity: p= 0.70, I(2)= 0%; absolute effect 55 fewer per 1000 [95% CI 61 fewer to 45 fewer], high quality of evidence). The most common adverse event associated with cinacalcet therapy was gastrointestinal side effects. Cinacalcet increased nausea (RR 2.16, 95% CI 1.46-3.21, absolute effect 158 more per 1000 [95% CI 82 more to 302 more]) and vomiting (RR 2.15, 95% CI 1.66-2.80, absolute effect 63 more per 1000 [95% CI 109 more to 171 more]). Cinacalcet treatment increased the rate of hypocalcemia (RR 6.0, 95% CI 3.65-9.87; heterogeneity: p= 0.71, I(2)= 0%, absolute effect 20 more per 1000 [95% CI 11 more to 36 more], high quality of evidence).
  
  
  CONCLUSIONS
  In the hands of clinicians participating in these studies, cinacalcet decreased the rate of parathyroidectomy but had no influence on mortality. Patients and clinicians can trade of the benefit of fewer parathyroidectomies against the adverse effects.
authors.affiliation: a Department of Clinical Epidemiology and Biostatistics , McMaster University , Hamilton , Ontario , Canada ;
authors.forename: Nigar
authors.initials: N
authors.lastname: Sekercioglu
authors.affiliation: a Department of Clinical Epidemiology and Biostatistics , McMaster University , Hamilton , Ontario , Canada ;|b The Michael G. DeGroote Institute for Pain Research and Care, McMaster University , Hamilton , Ontario , Canada ;|c Department of Anesthesia , McMaster University , Hamilton , Ontario , Canada ;
authors.forename: Jason W
authors.initials: JW
authors.lastname: Busse
authors.affiliation: d Departmant of Geography , Western University , London , Ontario , Canada ;
authors.forename: M Fatih
authors.initials: MF
authors.lastname: Sekercioglu
authors.affiliation: a Department of Clinical Epidemiology and Biostatistics , McMaster University , Hamilton , Ontario , Canada ;|e Faculty of Medicine , University of Toronto , Toronto , Ontario , Canada ;
authors.forename: Arnav
authors.initials: A
authors.lastname: Agarwal
authors.affiliation: f Department of Economics , McMaster University , Hamilton , Ontario , Canada ;
authors.forename: Shaun
authors.initials: S
authors.lastname: Shaikh
authors.affiliation: g Pharmaceutical Sciences Master Course , University of Sorocaba, UNISO , Sorocaba , Brazil ;
authors.forename: Luciane Cruz
authors.initials: LC
authors.lastname: Lopes
authors.affiliation: a Department of Clinical Epidemiology and Biostatistics , McMaster University , Hamilton , Ontario , Canada ;|h Department of Internal Medicine , University of Missouri-Kansas City , Kansas City , MO , USA ;|i Department of Biomedical and Health Informatics , University of Missouri-Kansas City , Kansas City , MO , USA ;
authors.forename: Reem A
authors.initials: RA
authors.lastname: Mustafa
authors.affiliation: a Department of Clinical Epidemiology and Biostatistics , McMaster University , Hamilton , Ontario , Canada ;|j Department of Medicine , McMaster University , Hamilton , Ontario , Canada ;
authors.forename: Gordon H
authors.initials: GH
authors.lastname: Guyatt
authors.affiliation: a Department of Clinical Epidemiology and Biostatistics , McMaster University , Hamilton , Ontario , Canada ;|k Department of Pediatrics and Anesthesia , McMaster University , Hamilton , Ontario , Canada ;|l Centre for Evaluation of Medicine, St Joseph's Healthcare-Hamilton , Hamilton , Ontario , Canada ;|m Biostatistics Unit, Father Sean O'Sullivan Research Centre , St Joseph's Healthcare , Hamilton , Ontario , Canada ;|n Population Health Research Institute, Hamilton Health Sciences , Hamilton , Ontario , Canada.
authors.forename: Lehana
authors.initials: L
authors.lastname: Thabane
mesh_terms: D057966:Calcimimetic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002318:Cardiovascular Diseases / Q000401:mortality; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000150:complications* / Q000188:drug therapy*; D000069449:Cinacalcet / Q000008:administration & dosage* / Q000009:adverse effects; D050723:Fractures, Bone / Q000453:epidemiology; D006760:Hospitalization; D006801:Humans; D010281:Parathyroid Hormone / Q000097:blood*; D016105:Parathyroidectomy
chemical_list: D057966:Calcimimetic Agents; D010281:Parathyroid Hormone; D000069449:Cinacalcet
keywords: Calcimimetics; chronic kidney disease; mineral and bone disorders; secondary hyperparathyroidism