Secondary hyperparathyroidism, an inevitable consequence of untreated chronic uraemia, is an adaptive response to sustained phosphate retention, failure of calcitriol synthesis and hypocalcaemia. For many years the therapeutic approach to these abnormalities has been relatively constant, comprising, respectively, dietary phosphate restriction with oral phosphate binders, replacement of the deficient active vitamin D ligand, and calcium supplementation by the oral and/or transdialytic route. The powerful calcaemic effects of the traditional 1 alpha hydroxylated vitamin D compounds has prompted a search for new compounds that might inhibit the parathyroids in more selectively, without exhibiting unwanted effects on intestine and perhaps bone as well. A number have shown promise at early stages of development but, while clearly highly effective in the setting of placebo controlled studies, they have shown little if any advantage when compared properly with existing standard therapy using calcitriol or alfacalcidol. To call these new agents non calcaemic is clearly misleading at the moment. One of the new compounds, paricalcitol, unexpectedly showed a significant survival advantage of paricalcitol treated patients compared with those receiving calcitriol. Other studies by the same group showed a striking survival advantage in patients receiving any parenteral vitamin D therapy over those receiving no vitamin D. These observations in many respects remain baffling. Cinacalcet, the first marketed calcimimetic agent, is now widely used in the treatment of hyperparathyroid states. Predictably, and in the knowledge that its principle action at the level of the parathyroid is to shift the sigmoidal calcium-PTH curve to the left, treatment of hyperparathyroid patients with cinacalcet is associated with simultaneous lowering of both PTH and calcium. In the setting of CKD patients with persisting hyperparathyroidism despite receiving standard therapy with vitamin D metabolites and phosphate binders, addition of cinacalcet resulted in substantially improved biochemical profiles, even in patients with severe disease.
06 - 07 Nov 2006
Society for Endocrinology