Vasculotropic effects of calcimimetics.
OBJECTIVE
At all stages of chronic kidney disease (CKD) cardiovascular death is the most prominent cause of mortality. Current treatment options are still not completely satisfactory in this group of high cardiovascular risk patients. Experimental data and clinical observations suggest a role of secondary hyperparathyroidism, hyperphosphatemia, and hypercalcemia in the genesis of cardiovascular complications of CKD. The ubiquitous expression of the calcium-sensing receptor, which is targeted by calcimimetics and the pleiotropic effects of calcimimetics, make this class of drugs potential candidates for cardiovascular intervention.


RESULTS
Recent experimental studies suggest that calcimimetics interfere with the development of vascular abnormalities in CKD and to some extent even reverse them. The effects of calcimimetics on the vasculature are, at least partially, independent of their effects on calcemia, phosphatemia, and parathyroid hormone concentration. The beneficial effects of calcimimetics on vascular calcification, arteriolar thickening, atherogenesis, and myocardial capillarization are well documented. In addition they have hypotensive and renoprotective actions.


CONCLUSIONS
Experimental models suggest beneficial effects of calcimimetics on cardiovascular disease. Although prospective clinical data are still lacking, retrospective data suggest cardiovascular benefit of calcimimetics even in humans. Clinical trials with calcimimetics evaluating hard cardiovascular end-points would be desirable.
Koleganova
Nadezda
N
Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany. nad_ko@gmx.de
Piecha
Grzegorz
G
Ritz
Eberhard
E
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002114:Calcinosis / Q000188:drug therapy / Q000517:prevention & control; D002118:Calcium / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000517:prevention & control; D006801:Humans; D010281:Parathyroid Hormone / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000378:metabolism; D012307:Risk Factors
D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D002118:Calcium