, Volume 67, Issue 14, pp 1981–1998 | Cite as

Vitamin D Receptor Activator Selectivity in the Treatment of Secondary Hyperparathyroidism

Understanding the Differences Among Therapies
  • Diego Brancaccio
  • Jürgen Bommer
  • Daniel Coyne
Current Opinion


Secondary hyperparathyroidism (SHPT) is a common and serious consequence of chronic kidney disease (CKD). SHPT is a complex condition characterised by a decline in 1,25-dihydroxyvitamin D and consequent vitamin D receptor (VDR) activation, abnormalities in serum calcium and phosphorus levels, parathyroid gland hyperplasia, elevated parathyroid hormone (PTH) secretion, and systemic mineral and bone abnormalities. There are three classes of drugs used for treatment of SHPT: (i) nonselective VDR activators or agonists (VDRAs); (ii) selective VDRAs; and (iii) calcimimetics. The VDRAs act on the VDR, whereas the calcimimetics act on the calcium-sensing receptor. Calcimimetics are commonly used in conjunction with VDRA therapy. By virtue of the differences in their chemical structure, the nonselective and selective VDRAs differ in their effects on gene expression, and ultimately parathyroid gland, bone and intestine function. Medications in all three classes are effective in suppression of PTH; however, clinical studies show that calcimimetics are associated with an unfavourable tolerability profile and hypocalcaemia, whereas nonselective VDRAs, and to a lesser extent selective VDRAs, are associated with dose-limiting hypercalcaemia and hyperphosphataemia. Selective VDRAs also have minimal undesirable effects on calcium absorption in the intestine, and calcium and phosphorus mobilisation in the bone compared with nonselective VDRAs. Calcium load in patients with CKD can lead to vascular calcification, accelerated progression of cardiovascular disease and increased mortality. High serum phosphorus levels are also associated with adverse effects on cardiorenal function and survival. Recent evidence suggests that VDRAs are associated with a survival benefit in CKD patients, with a more favourable effect with selective VDRAs than nonselective VDRAs. Paricalcitol, a selective VDRA, is reported to exert specific effects on gene expression in various cell types that are involved in vascular calcification and the development of coronary artery disease. This article examines the molecular mechanisms that determine selectivity of VDRAs, and reviews the evidence for clinical efficacy, safety and survival associated with the three drug classes used for treatment of SHPT in CKD patients.


Chronic Kidney Disease Chronic Kidney Disease Patient Chronic Kidney Disease Stage Peritoneal Dialysis Patient Cinacalcet 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors wish to express their gratitude to Dr A. Ferreira, MD, PhD, (Hospital Curry Cabral, Lisbon, Portugal), for his valuable knowledge and understanding of bone mineral disorder, and Amy J. Yellen-Shaw, PhD, for her editorial assistance. The funding for the editorial assistance was provided by Abbott. Dr Brancaccio has received honoraria for scientific presentations from Abbott, Amgen and Shire Pharmaceuticals. Dr Bommer has received honoraria for lectures from Amgen and Abbott. Dr Coyne has received honoraria for consultancies from Abbott, INEOS and Amgen, and grants from Abbott and Amgen.


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Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Diego Brancaccio
    • 1
  • Jürgen Bommer
    • 2
  • Daniel Coyne
    • 3
  1. 1.Renal DivisionUniversity of Milan, Ospedale San PaoloMilanoItaly
  2. 2.Medizinische Universitatsklinik HeidelbergHeidelbergGermany
  3. 3.Division of Renal DiseasesWashington University School of MedicineMissouriUSA

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