The impact of calcimimetics on mineral metabolism and secondary hyperparathyroidism in end-stage renal disease.
The impact of calcimimetics on mineral metabolism and secondary hyperparathyroidism in end-stage renal disease. Secondary hyperparathyroidism is often complicated by elevations in calcium and phosphorus either as a result of the disease per se or due to toxicity from current therapeutic options. These disturbances in mineral metabolism limit the successfulness of therapy and have been implicated as contributing to the development and progression of vascular calcification, an important and often overlooked component of cardiovascular disease in patients on dialysis. Phosphorus, active vitamin D, and calcium all play important roles in the pathogenesis of secondary hyperparathyroidism; however, serum calcium is the primary regulator of minute-to-minute parathyroid hormone secretion. Small changes in serum calcium are detected by a cell surface calcium sensing receptor that has recently been cloned. Calcimimetic agents modulate the activity of the calcium-sensing receptor and result in profound reductions in levels of circulating parathyroid hormone. Additionally, these agents result in decreases in serum calcium, phosphorus, and calcium-phosphorus product. Recently completed phase 2 clinical trials with the second-generation calcimimetic agent cinacalcet HCl confirm that this agent represents a safe and effective novel therapeutic agent which has the potential to dramatically alter the treatment and complications associated with secondary hyperparathyroidism in patients on dialysis.
Block
Geoffrey A
GA
Denver Nephrologists, Denver, Colorado, USA. gblock@denverneph.net
D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000819:agonists*; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000188:drug therapy*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy*; D007676:Kidney Failure, Chronic / Q000150:complications*; D011073:Polyamines / Q000627:therapeutic use; D000071228:Polyelectrolytes; D014807:Vitamin D / Q000627:therapeutic use
D002118:Calcium; D011073:Polyamines; D000071228:Polyelectrolytes; D014807:Vitamin D