Calcimimetics and outcomes in CKD

In the past decade, several experimental studies demonstrated an inhibitory effect of calcimimetics on the progression of vascular calcification in animals with chronic kidney disease (CKD), in keeping with the expression of the calcium-sensing receptor (CaR) in vascular tissue. In addition, calcimimetics were also found to prevent the arterial remodeling caused by CKD and to slow the progression of atherosclerosis in uremic rats and mice, respectively. The mode of action of these CaR modulators could be both via a better control of secondary hyperparathyroidism and direct effects on the vessel wall. Two main clinical trials, ADVANCE and EVOLVE, recently evaluated in patients with CKD stage 5D the effects of the calcimimetic cinacalcet on the progression of vascular calcification and hard cardiovascular outcomes, respectively. Both trials missed their respective primary end point by intent-to-treat analysis although by other prespecified analyses, including adjustment for baseline characteristics, there was strong suggestive evidence in favor of reductions in risk, in agreement with numerous experimental studies. Further clinical trials are needed to settle this issue definitively.