This article appraisal is part of the EMiNEM Bone and Mineral Metabolism Series. Click here to reach the EMiNEM homepage on UKidney

Kidney Int. 2010 Sep;78(6):578-89

Study Hypothesis:

Prescribing cinacalcet to a large hemodialysis population with secondary hyperparathyroidism would be associated with improved survival.

Study Design and Study Population

Patient data such as demographics, weight, height, laboratory values, dialysis treatment, vascular access, iv vitamin D use, home medications, censoring (mortality, outside transfer, modality change) and insurance coverage was obtained from DaVita. Data were linked to the Centre for Medicare and Medicaid Services end stage renal disease (CMS ESRD) database by the USRDS.   The CMS ESRD data provided information on ESRD initiation date, comorbid conditions, ESRD cause, medical claims (which include hospitalization information) and mortality date and cause. All prevalent hemodialysis patients greater than 18 years old and have survived 90 days as of August 1 2004 were selected and data were collected prospectively through December 31, 2006.

Intervention or observation

Cinacalcet exposure was defined as dichotomous variable on the basis of the presence or absence of cinacalcet prescription during the study period. Once patients started cinacalcet, they were considered cinacalcet patients until the end of the study period.

Primary End Point:

All cause and cardiovascular mortality

Results:

Table one outlines the baseline demographics and health information between cinacalcet patients and non cinacalcet patients. Patients with cinacalcet prescriptions were: younger, less likely to have diabetes, African American, longer dialysis vintage and less likely to be hospitalized. These patients also had higher baseline Calcium and PTH levels and were more likely to receive sevelamer as a phosphate binder.

The unadjusted all cause mortality hazard ratio was 0.73, with CI 0.68-0.78, p<0.001 and the unadjusted cardiovascular mortality hazard ratio was 0.78 with CI 0.71-0.86, P<0.001). The adjusted models showed similar hazard ratios of 0.74 with CI 0.67-0.83 and 0.76 with CI 0.66-0.86, P<0.001, respectively.

Methodological Assessment

This was an observational study and thus cannot determine cause and effect. There is also the possibility of confounding by indication and the question of external validity as iv vitamin D use was an inclusion criteria and predominantly USA data with a large proportion of African Americans. Furthermore 43% of patients with PTH > 600ng/L did not receive treatment with cinacalcet. The non treated group also had significant higher CAD, CHF and PVD and lower use of beta blockers and Ace inhibitors. Finally treated patients had longer dialysis vintage at first inclusion and therefore there may be a “survivor bias”.

Impact on Practice

Cinacalcet lowers calcium, phosphorous and PTH levels. It appears that prescription of cinacalcet in patients using iv calcitriol may be associated with reduction in all cause mortality and cardiovascular mortality. However, the cost of cinacalcet will prohibit its use in many provinces in Canada. The results of the randomized placebo-controlled trial (EVOLVE) will provide hard outcomes data to hopefully aide clinicians in cinacalcet’s role in CKD bone mineral metabolism therapy.


Reviewed by Reviewed by Marisa Battistella

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