Management of secondary hyperparathyroidism.
Secondary hyperparathyroidism (SHPT) remains an inevitable consequence of untreated chronic uremia. It is the result of a combination of phosphate (P) retention, failure of calcitriol synthesis, and hypocalcemia. Therapies used to correct these abnormalities, namely active vitamin D replacement, calcium (Ca) supplementation, and phosphate (P) restriction, have moderate efficacy but are prone to unacceptable side-effects. However, there have been new developments in the control of P, vitamin D replacement and modulation of the Ca sensing receptor (CaSR) using calcimimetics. Sevelamer, and in the near future lanthanum, are offering a reasonable level of P control without the toxicities inherent with either aluminum- or Ca-based phosphate binders, and other phosphate binders are in development. 'Non calcemic' vitamin D metabolites include 22-oxacalcitriol, paricalcitol, and doxercalciferol. In various experimental models 22-oxacalcitriol, in particular, exhibits impressive suppression of parathyroid hormone (PTH) with minimal calcemia, although it has been less impressive when compared with calcitriol in controlled studies in hemodialysis (HD) patients. The advantages of these agents over conventional treatment with calcitriol or alfacalcidol remain uncertain. Cinacalcet, a calcimimetic agent that up-regulates the sensitivity of the CaSR in parathyroid and other cells, is a new type of therapy for SHPT that simultaneously reduces the concentrations of PTH, Ca, and P in HD patients, enabling a significant number to achieve K/DOQI or other national guidelines. The extent to which this new therapy will improve clinical outcomes remains uncertain. In conclusion, with the advent of new therapies the emphasis in the management of SHPT has evolved to incorporate reduction of Ca loading, control of PTH within specific target ranges, and avoidance of hypercalcemia, hyperphosphatemia and elevation of the calcium phosphorus product.
Cunningham
John
J
The Center for Nephrology, The Royal Free and University College Medical School, London, UK. drjohncunningham@aol.com
D002118:Calcium / Q000097:blood; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000188:drug therapy*; D010758:Phosphorus / Q000097:blood
D010758:Phosphorus; D002118:Calcium