Journal Club: Cinacalcet

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Elevations in serum calcium, phosphorous and PTH have all been associated with increased morbidity and mortality in observational studies of ESRD patients. A variety of agents are available to control these serum parameters including phosphorous binders, intravenous vitamin D and calcimemetics. None unfortunately, have been shown in randomized prospective fashion to impact mortality. Cinacalcet, a calcimimetic works by increasing the sensitivity of the calcium-sensing receptor to extracellular calcium. When calcium binds these receptors on the parathyroid gland PTH release is inhibited.

Additionally, cinacalcet leads to lower levels of serum calcium and phosphorous as opposed to intravenous vitamin D which tends to raise these values. Given cinacalcet moves all the serum values in what would seem be helpful directions a recent observational paper in KI took a look at its impact on mortality.
To do this Block and colleagues looked at 5976 ESRD hemodialysis patients from DaVita who had received cinacalcet and compared them with 19,174 who did not. Outcomes were then checked in USRDS.
All patients had secondary hyperparathyroidism as defined by the use of IV vitamin D at baseline.
A multivariate adjusted analysis showed a 26% reduction in all cause mortality in patients who took cinacalcet compared with those who did not. Cardiovascular mortality was also reduced significantly but interestingly only accounted for 44% and 46% of deaths in the cinacalcet and non-cinacalcet groups respectively. Patients in the cinacalcet group at baseline tended to be younger, have less diabetes, fewer days of hospitalization and higher BMIs and albumin.
Although the authors attempted to adjust for these and other known confounders this observational study has a number of potential caveats:
  • Confounding by indication (we don’t know what clinical factors led to cincalcet presciption)
  • Lead time bias (patients in the cinacalcet group may have for some reason been earlier in the disease process at baseline and thus appeared to live longer)
It should also be noted that the study was partially funded by Amgen (the maker of the Sensipar) and that the first author is both a consultant and advisor for them.
Given the above this paper will not change my current practice. Hopefully  these results will be supported by the upcoming multicenter randomized placebo controlled EVOLVE trial which is examining the impact of cinacalcet on a primary composite outcome of all cause mortality or non fatal cardiovascular event.

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