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

Wetmore JB, Quarles LD - Int J Nephrol Renovasc Dis (2008)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Nephrology, University of Kansas Medical Center, Kansas City, KS, USA;

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Competing therapeutic strategies for treatment of secondary hyperparathyroidism, with advantages and disadvantages.Abbreviations: PTH, parathyroid hormone; SHPT, secondary hyperparathyroidism.
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f1-ijnr_01_05: Competing therapeutic strategies for treatment of secondary hyperparathyroidism, with advantages and disadvantages.Abbreviations: PTH, parathyroid hormone; SHPT, secondary hyperparathyroidism.

Mentions: In Figure 1, we illustrate two potential therapeutic approaches to SHPT (one calcimimetic-based, the other vitamin D analog-based), and list relevant advantages and disadvantages of each. The Figure represents less a specific protocol than an overall conceptualization of possible treatment strategies. Patients with low calcium levels (ie, <8.4 mg/dL) might best avoid the potential for cinacalcet-induced hypocalcemia, at least until low doses of activated vitamin D compounds increase serum calcium to the normal range, while those with high serum calcium ought to avoid large doses of activated vitamin D compounds. For patients whose calcium levels fall within the “acceptable” NKF K/DOQI range, namely 8.4 to 9.5 mg/dL, the approaches have many similarities. In both, dietary phosphorous restriction is important, and oral phosphate binders critical. Non-calcium-based binders are generally preferred in either approach, given the mounting evidence that non-calcium based binders are associated with less vascular calcification4–7,108 and perhaps improved survival,109 although the latter finding requires replication and extension in true blinded RCTs.


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

Wetmore JB, Quarles LD - Int J Nephrol Renovasc Dis (2008)

Competing therapeutic strategies for treatment of secondary hyperparathyroidism, with advantages and disadvantages.Abbreviations: PTH, parathyroid hormone; SHPT, secondary hyperparathyroidism.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108756&req=5

f1-ijnr_01_05: Competing therapeutic strategies for treatment of secondary hyperparathyroidism, with advantages and disadvantages.Abbreviations: PTH, parathyroid hormone; SHPT, secondary hyperparathyroidism.
Mentions: In Figure 1, we illustrate two potential therapeutic approaches to SHPT (one calcimimetic-based, the other vitamin D analog-based), and list relevant advantages and disadvantages of each. The Figure represents less a specific protocol than an overall conceptualization of possible treatment strategies. Patients with low calcium levels (ie, <8.4 mg/dL) might best avoid the potential for cinacalcet-induced hypocalcemia, at least until low doses of activated vitamin D compounds increase serum calcium to the normal range, while those with high serum calcium ought to avoid large doses of activated vitamin D compounds. For patients whose calcium levels fall within the “acceptable” NKF K/DOQI range, namely 8.4 to 9.5 mg/dL, the approaches have many similarities. In both, dietary phosphorous restriction is important, and oral phosphate binders critical. Non-calcium-based binders are generally preferred in either approach, given the mounting evidence that non-calcium based binders are associated with less vascular calcification4–7,108 and perhaps improved survival,109 although the latter finding requires replication and extension in true blinded RCTs.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Nephrology, University of Kansas Medical Center, Kansas City, KS, USA;

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus