The recent introduction of calcimimetics, a novel class of therapeutic agents, has led to a change in the treatment strategy of
secondary hyperparathyroidism in patients with
end-stage renal disease. In initial acute studies in chronic
hemodialysis patients, the calcimimetic
cinacalcet was shown to reduce plasma intact
parathyroid hormone within hours, followed by a rapid, profound decrease in plasma
calcium and a minor decrease in plasma
phosphorus. Subsequent reports showed that the long-term administration of
cinacalcet to such patients proved to be superior to standard
therapy in controlling secondary uremic
hyperparathyroidism, in that it was able to induce a decrease in both plasma intact
parathyroid hormone and the
calcium x
phosphorus product, in contrast to the effects of active
vitamin D sterols. This allowed the achievement of the guideline treatment targets proposed by the National Kidney Foundation
Kidney Disease Outcomes Quality Initiative in a much larger proportion of dialysis patients than standard
therapy did. Moreover, the effect of
cinacalcet is long-lasting. An important question is that of
cinacalcet's effects on patient outcomes, which is still lacking. A similar lack of information exists for most other treatment modalities given to correct the
mineral and bone disorder of
chronic kidney disease. A post-hoc analysis of four clinical trials combined done in
hemodialysis patients showed that randomization to
cinacalcet led to significant reductions in the risk of
parathyroidectomy, fracture, and cardiovascular hospitalization. To obtain a definitive answer to this question, including patient survival, we will have to wait for the results of prospective, randomized controlled trials. In pre-clinical studies performed in rats with
chronic renal failure, the administration of the calcimimetic
NPS R-568 at the time of
uremia induction allowed the prevention of parathyroid
hyperplasia, and the reversal of already established
hyperplasia as well. Perhaps more important from the clinical point of view,
NPS R-568 also appeared to allow reversal of
osteitis fibrosa in uremic rats and reduction of aortic calcification and
atherosclerosis in uremic rats and mice. In conclusion, the clinical introduction of
cinacalcet allows for better control of
secondary hyperparathyroidism in dialysis patients as compared to standard
therapy, based on surrogate
biochemical markers. Hopefully, in the future, this improvement will be shown to be associated with better patient outcomes for the treatment of fractures and cardiovascular morbidity and mortality.