Treatment of secondary hyperparathyroidism in kidney disease: what we know and do not know about use of calcimimetics and vitamin D analogs

There is a growing understanding of the pathophysiology of secondary hyperparathyroidism (SHPT) and a recent emergence of new agents for SHPT treatment in patients with advanced kidney disease. At the same time, appreciation that mineral metabolic derangements promote vascular calcification and contribute to excess mortality, along with recognition of potentially important "non-classical" actions of vitamin D, have prompted the nephrology community to reexamine the use of various SHPT treatments, such as activated vitamin D sterols, phosphate binders, and calcimimetics. In this review, the evidence for treatment of SHPT with calcimimetics and vitamin D analogs is evaluated, with particular consideration given to recent clinical trials that have reported encouraging findings with cinacalcet use. Additionally, several controversies in the pathogenesis and treatment of SHPT are explored. The proposition that calcitriol deficiency is a true pathological state is challenged, the relative importance of the vitamin D receptor and the calcium sensing receptor in parathyroid gland function is summarized, and the potential relevance of non-classical actions of vitamin D for patients with advanced renal disease is examined. Taken collectively, the balance of evidence now supports a treatment paradigm in which calcimimetics are the most appropriate primary treatment for SHPT in the majority of end stage renal disease patients, but which nevertheless acknowledges an important role for modest doses of activated vitamin D sterols.