Drugs

, 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
Current Opinion

Abstract

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.

Keywords

Chronic Kidney Disease Chronic Kidney Disease Patient Chronic Kidney Disease Stage Peritoneal Dialysis Patient Cinacalcet 

Notes

Acknowledgements

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.

References

  1. 1.
    Slatopolsky E, Brown A, Dusso A. Pathogenesis of secondary hyperparathyroidism. Kidney Int 1999; 56 Suppl. 73: S14–9CrossRefGoogle Scholar
  2. 2.
    Andress DL. Vitamin D treatment in chronic kidney disease. Semin Dial 2005; 18: 315–21PubMedCrossRefGoogle Scholar
  3. 3.
    Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002; 62: 245–52PubMedCrossRefGoogle Scholar
  4. 4.
    Goodman WG, Goldin J, Kuizon BD, et al. Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 2001; 342: 1478–83CrossRefGoogle Scholar
  5. 5.
    Kalpakian MA, Mehrota R. Vascular calcification and disordered mineral metabolism in dialysis patients. Semin Dial 2007; 20: 139–43PubMedCrossRefGoogle Scholar
  6. 6.
    London GM, Geurin AP, Verbeke FH, et al. Mineral metabolism and arterial functions in end-stage renal disease: potential role of 25-hydroxyvitamin D deficiency. J Am Soc Nephrol 2007; 18: 613–20PubMedCrossRefGoogle Scholar
  7. 7.
    Coen G, Ballanti P, Bonucci E, et al. Renal osteodystrophy in predialysis and hemodialysis patients: comparison of histologic patterns and diagnostic predictivity of intact PTH. Nephron 2002; 91: 103–11PubMedCrossRefGoogle Scholar
  8. 8.
    Moe SM, Drüeke T, Cunninghham J, et al. Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Gobal Outcomes (KDIGO). Kidney Int 2006; 69: 1945–53PubMedCrossRefGoogle Scholar
  9. 9.
    Block GA, Klassen PS, Lazarus JM, et al. Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 2004; 15: 2208–18PubMedCrossRefGoogle Scholar
  10. 10.
    Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351: 1296–305PubMedCrossRefGoogle Scholar
  11. 11.
    Hamdy NA, Kanis JA, Beneton MN, et al. Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. BMJ 1995; 310: 358–63PubMedCrossRefGoogle Scholar
  12. 12.
    Maung HM, Elangovan L, Frazao JM, et al. Efficacy and side effects of intermittent intravenous and oral doxercalciferol (1alpha-hydroxyvitamin D2) in dialysis patients with secondary hyperparathyroidism: a sequential comparison. Am J Kidney Dis 2001; 37: 532–43PubMedCrossRefGoogle Scholar
  13. 13.
    Nordal KP, Dahl E. Low dose calcitriol versus placebo in patients with predialysis chronic renal failure. J Clin Endocrinol Metab 1988; 67: 929–36PubMedCrossRefGoogle Scholar
  14. 14.
    Block GA, Port FK. Re-evaluation of risks associated with hyperphosphatemia and hyperparathyroidism in dialysis patients: recommendations for a change in management. Am J Kidney Dis 2000; 35: 1226–37PubMedCrossRefGoogle Scholar
  15. 15.
    Ma JN, Osinski M, Rose M, et al. Effects of VDR activators on intestinal calcium transport [abstract no. SA-PO613]. J Am Soc Nephrol 2004; 115: 437AGoogle Scholar
  16. 16.
    Rocaltrol® (calcitriol). Full prescribing information. Nutley (NJ); Roche Laboratories Inc., 2004Google Scholar
  17. 17.
    Sensipar® (cinacalcet HCl). Full prescribing information. Thousand Oaks (CA); Amgen Inc., 2004Google Scholar
  18. 18.
    Zemplar® (paricalcitol). Full prescribing information. North Chicago (IL); Abbott Laboratories, 2005Google Scholar
  19. 19.
    Tentori F, Hunt WC, Stidley CA, et al. Mortality risk among hemodialysis patients receiving different vitamin D analogs. Kidney Int 2006 Nov; 70(10): 1858–65PubMedCrossRefGoogle Scholar
  20. 20.
    Hudson JQ. Secondary hyperparathyroidism in chronic kidney disease: focus on clinical consequences and vitamin D therapies. Ann Pharmacother 2006; 40: 1584–93PubMedCrossRefGoogle Scholar
  21. 21.
    Jones G, Strugnell SA, DeLuca HF. Current understanding of the molecular actions of vitamin D. Physiol Rev 1998; 78: 1193–231PubMedGoogle Scholar
  22. 22.
    Andress DL. Vitamin D in chronic kidney disease: a systemic role for selective vitamin D receptor activation. Kidney Int 2005; 69: 33–43CrossRefGoogle Scholar
  23. 23.
    Dusso AS, Thadhani R, Slatopolsky E. Vitamin D receptor and analogs. Semin Nephrol 2004; 24: 10–6PubMedCrossRefGoogle Scholar
  24. 24.
    Martin PY, Gonzalez E, Lindberg JS, et al. Paricalcitol dosing according to body weight or severity of hyperparathyroidism: a double-blind, multicenter, randomized study. Am J Kidney Dis 2001; 38 Suppl. 5: S57–63PubMedCrossRefGoogle Scholar
  25. 25.
    Brown AJ, Coyne DW. Vitamin D analogs: new therapeutic agents for secondary hyperparathyroidism. Treat Endocrinol 2002; 1: 313–27PubMedCrossRefGoogle Scholar
  26. 26.
    Hirata M, Endo K, Katsumata K, et al. A comparison between 1,25-dihydroxy-22-oxavitamin D(3) and 1,25-dihydroxyvitamin D(3) regarding suppression of parathyroid hormone secretion and calcaemic action. Nephrol Dial Transplant 2002; 17 Suppl. 10: 41–5PubMedCrossRefGoogle Scholar
  27. 27.
    Hirata M, Katsumata K, Endo K, et al. In subtotally nephrectomized rats 22-oxacalcitriol suppresses parathyroid hormone with less risk of cardiovascular calcification or deterioration of residual renal function than 1,25(OH)2 vitamin D3. Nephrol Dial Transplant 2003 Sep; 18(9): 1770–6PubMedCrossRefGoogle Scholar
  28. 28.
    Carlberg C, Quack M, Herdick M, et al. Central role of VDR conformations for understanding selective actions of vitamin D3 analogues. Steroids 2001; 66: 213–21PubMedCrossRefGoogle Scholar
  29. 29.
    Barthel TK, Mathern DR, Whitfield GK, et al. 1,25-dihydroxyvitamin D3/VDR-mediated induction of FGF23 as well as transcriptional control of other anabolic and catabolic genes that orchestrate the regulation of phosphate and calcium mineral metabolism. J Steroid Biochem Mol Biol 2007; 103: 381–8PubMedCrossRefGoogle Scholar
  30. 30.
    Issa LL, Leong GM, Sutherland RL, et al. Vitamin D analogue-specific recruitment of vitamin D receptor coactivators. J Bone Miner Res 2002; 17: 879–90PubMedCrossRefGoogle Scholar
  31. 31.
    Quack M, Carlberg C. Selective recognition of vitamin D receptor conformations mediates promoter selectivity of vitamin D analogs. Mol Pharmacol 1999; 55: 1077–87PubMedGoogle Scholar
  32. 32.
    Takeyama K-I, Masuhiro Y, Fuse H, et al. Selective interaction of vitamin D receptor with transcriptional coactivators by a vitamin D analog. Mol Cell Biol 1999; 19: 1049–55PubMedGoogle Scholar
  33. 33.
    Wu-Wong JR, Nakane M, Ma J, et al. Effects of vitamin D analogs on gene expression profiling in human coronary artery smooth muscle cells. Atherosclerosis 2006; 186: 20–8PubMedCrossRefGoogle Scholar
  34. 34.
    Kroeger PE, Ruan X, Burton GR, et al. Microarray analysis of differentiated Caco-2 colon carcinoma cells treated with VDR activators [abstract no. TH-PO153]. American Society of Nephrology (ASN) 38th Renal Week Meeting; 2005 Nov 8–13; Philadelphia (PA)Google Scholar
  35. 35.
    Slatopolsky E, Finch J, Ritter C, et al. Effects of 19-nor-1,25(OH)2D2, a new analogue of calcitriol, on secondary hyperparathyroidism in uremic rats. Am J Kidney Dis 1998; 32 Suppl. 2: S40–7PubMedCrossRefGoogle Scholar
  36. 36.
    Slatopolsky E, Cozzolino M, Finch JL. Differential effects of 19-nor-1,25-(OH)2D3 and 1α-hydroxyvitamin D2 on calcium and phosphorus in normal and uremic rats. Kidney Int 2002; 62: 1277–84PubMedCrossRefGoogle Scholar
  37. 37.
    Nakane M, Ma J, Rose AE, et al. Differential effects of vitamin D analogs on calcium transport. J Steroid Biochem Mol Biol 2007; 103: 84–9PubMedCrossRefGoogle Scholar
  38. 38.
    Nakane M, Fey TA, Dixon DB, et al. Differential effects of vitamin D analogs on bone formation and resorption. J Steroid Biochem Mol Biol 2006; 98: 72–7PubMedCrossRefGoogle Scholar
  39. 39.
    Holliday LS, Gluck SL, Slatopolsky E, et al. 1,25-dihydroxy-19-nor-vitamin D2, a vitamin D analog with reduced bone resorbing activity in vitro. J Am Soc Nephrol 2000; 11: 1857–64PubMedGoogle Scholar
  40. 40.
    Zierold C, Mings JA, DeLuca HF. Regulation of 25-hydroxyvitamin D3-24-hydroxylase mRNA by 1,25-dihydroxyvitamin D3 and parathyroid hormone. J Cell Biochem 2003; 88: 234–7PubMedCrossRefGoogle Scholar
  41. 41.
    Zierold C, Mings JA, DeLuca HF. 19nor-1,25-dihydroxyvitamin D2 specifically induces CYP3A9 in rat intestine more strongly than 1,25-dihydroxyvitamin D3 in vivo and in vitro. Mol Pharmacol 2006; 69: 1740–7PubMedCrossRefGoogle Scholar
  42. 42.
    Petrie MS, Harrell TE, Schwartz GG, et al. Production of plasminogen activator inhibitor-1 (PAI-1) by endothelial cells: differential responses to calcitriol and paricalcitol. J Thromb Haemost 2004 Dec; 2(12): 2266–7PubMedCrossRefGoogle Scholar
  43. 43.
    Nordt TK, Peter K, Ruef J, et al. Plasminogen activator inhibitor type-1 (PAI-1) and its role in cardiovascular disease. Thromb Haemost 1999; 82 Suppl. 1: 14–8PubMedGoogle Scholar
  44. 44.
    Lund R, Tian J, Melnick J, et al. Differential effects of paricalcitol and calcitriol on intestinal calcium absorption in hemodialysis patients [abstract no. SP-607]. XLIII European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress; 2006 Jul 15–18; GlasgowGoogle Scholar
  45. 45.
    Coyne DW, Grieff M, Ahya SN, et al. Differential effects of acute administration of 19-Nor-1,25-dihydrocy-vitamin D2 and 1,25-dihydroxy-vitamin D3 on serum calcium and phosphorus in hemodialysis patients. Am J Kidney Dis 2002; 40: 1283–8PubMedCrossRefGoogle Scholar
  46. 46.
    Joist HE, Ahya SN, Giles K, et al. Differential effects of very high doses of doxercalciferol and paricalcitol on serum phosphorus in hemodialysis patients. Clin Nephrol 2006 May; 65(5): 335–41PubMedGoogle Scholar
  47. 47.
    Sprague SM, Llach F, Amdahl M, et al. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int 2003 Apr; 63(4): 1483–90PubMedCrossRefGoogle Scholar
  48. 48.
    Moriniere P, El Esper N, Viron B, et al. Improvement of severe secondary hyperparathyroidism in dialysis patients by intravenous 1α(OH) vitamin D3, oral CaCO3 and low dialysate calcium. Kidney Int 1993; 43 Suppl. 41: S121–4Google Scholar
  49. 49.
    Brandi L, Daugaard H, Tvedegaard E, et al. Long-term suppression of secondary hyperparathyroidism by intravenous 1α hydroxyvitamin D3 in patients on chronic hemodialysis. Am J Nephrol 1992; 12: 311–8PubMedCrossRefGoogle Scholar
  50. 50.
    Rix M, Eskildsen P, Olgaard K. Effect of 18 months of treatment with alfacalcidol on bone in patients with mild to moderate chronic renal failure. Nephrol Dial Transplant 2004; 19: 870–6PubMedCrossRefGoogle Scholar
  51. 51.
    Coburn JW, Maung HM, Elangovan L, et al. Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4. Am J Kidney Dis 2004 May; 43(5): 877–90PubMedCrossRefGoogle Scholar
  52. 52.
    Ross EA, Tian J, Abboud H, et al. Paricalcitol capsules for the treatment of secondary hyperparathyroidism in patients on HD or PD [abstract no. SA-PO551]. American Society of Nephrology (ASN) 39th Renal Week Meeting; 2006 Nov 14–19; San Diego (CA)Google Scholar
  53. 53.
    Martin KJ, Gonzalez EA, Gellens M, et al. 19-Nor-1-alpha-25-dihydroxyvitamin D2 (paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis. J Am Soc Nephrol 1998 Aug; 9(8): 1427–32PubMedGoogle Scholar
  54. 54.
    Lindberg J, Martin KJ, Gonzalez EA, et al. A long-term, multicenter study of the efficacy and safety of paricalcitol in end-stage renal disease. Clin Nephrol 2001 Oct; 56(4): 315–23PubMedGoogle Scholar
  55. 55.
    Coyne D, Acharya M, Qiu P, et al. Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD. Am J Kidney Dis 2006 Feb; 47(2): 263–76PubMedCrossRefGoogle Scholar
  56. 56.
    Gonzalez EA, Sachdeva A, Oliver DA, et al. Vitamin D insufficiency and deficiency in chronic kidney disease: a single center observational study. Am J Nephrol 2004 Sep–Oct; 24(5): 503–10PubMedCrossRefGoogle Scholar
  57. 57.
    Peterlik M, Cross HS. Vitamin D and calcium deficits predispose for multiple chronic diseases. Eur J Clin Invest 2005 May; 35(5): 290–304PubMedCrossRefGoogle Scholar
  58. 58.
    LaClair RE, Hellman RN, Karp SL, et al. Prevalence of calcidiol deficiency in CKD: a cross-sectional study across latitudes in the United States. Am J Kidney Dis 2005 Jun; 45(6): 1026–33PubMedCrossRefGoogle Scholar
  59. 59.
    Tan X, Li Y, Liu Y. Paricalcitol attenuates renal interstitial fibrosis in obstructive nephropathy. J Am Soc Nephrol 2006 Dec; 17(12): 3382–93PubMedCrossRefGoogle Scholar
  60. 60.
    Mizobuchi M, Finch JL, Martin DR, et al. Differential effects of vitamin D receptor activators on vascular calcification in uremic rats. Kidney Int. Epub 2007 Jun 27Google Scholar
  61. 61.
    Li YC, Kong J, Wei M, et al. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 2002 Jul; 110(2): 229–38PubMedGoogle Scholar
  62. 62.
    Qiao G, Kong J, Uskokovic M, et al. Analogs of 1alpha,25-dihydroxyvitamin D(3) as novel inhibitors of renin biosynthesis. J Steroid Biochem Mol Biol 2005 Jun; 96(1): 59–66PubMedCrossRefGoogle Scholar
  63. 63.
    Fryer RM, Rakestraw PA, Nakane M, et al. Differential inhibition of renin mRNA expression by paricalcitol and calcitriol in C57/BL6 mice. Nephron Physiol 2007; 106(4): 76–81CrossRefGoogle Scholar
  64. 64.
    Balint E, Marshall CF, Sprague SM. Effect of the vitamin D analogues paricalcitol and calcitriol on bone mineral in vitro. Am J Kidney Dis 2000 Oct; 36(4): 789–96PubMedCrossRefGoogle Scholar
  65. 65.
    Jokihaara J, Porsti I, Pajamaki I, et al. Paricalcitol [19-nor-1,25-(OH)2D2] in the treatment of experimental renal bone disease. J Bone Miner Res 2006 May; 21(5): 745–51PubMedCrossRefGoogle Scholar
  66. 66.
    Mittman N, Khanna R, Chattopadhyay J, et al. Paricalcitol therapy for secondary hyperparathyroidism in patients on maintenance hemodialysis previously treated with calcitriol: a single-center crossover study. Kidney Int 2006; 70: S64–7CrossRefGoogle Scholar
  67. 67.
    Desiraju B, Mittman N, Meyer K, et al. Treatment of secondary hyperparathyroidism (SHPT) with paricalcitol (P) versus calcitriol (C): a two year, single center crossover comparison [abstract no. SA-PO1009]. American Society of Nephrology (ASN) 39th Renal Week Meeting; 2006 Nov 14–19; San Diego (CA)Google Scholar
  68. 68.
    Vervloet MG, Grooteman MP, Ter Wee PM. Improved parathyroid hormone levels after conversion from intravenous alfa-calcidol to intravenous paricalcitol [abstract no. PUB343]. American Society of Nephrology (ASN) 39th Renal Week Meeting; 2006 Nov 14–19; San Diego (CA)Google Scholar
  69. 69.
    Llach F, Yudd M. Paricalcitol in dialysis patients with calcitriol-resistant secondary hyperparathyroidism. Am J Kidney Dis 2001 Nov; 38 (5 Suppl. 5): S45–50PubMedCrossRefGoogle Scholar
  70. 70.
    Hammerland LG, Garrett JE, Hung BC, et al. Allosteric activation of the Ca2+ receptor expressed in Xenopus laevis oocytes by NPS 467 or NPS 568. Mol Pharmacol 1998; 53: 1083–8PubMedGoogle Scholar
  71. 71.
    Block GA, Martin KJ, de Francisco ALM, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 2004; 350: 1516–25PubMedCrossRefGoogle Scholar
  72. 72.
    Lindberg JS, Culleton B, Wong G, et al. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study. J Am Soc Nephrol 2005; 16: 800–7PubMedCrossRefGoogle Scholar
  73. 73.
    Moe SM, Chertow GM, Coburn JW, et al. Achieving NKF-K/DOQI™ bone metabolism and disease treatment goals with cinacalcet HCl. Kidney Int 2005; 67: 760–71PubMedCrossRefGoogle Scholar
  74. 74.
    Moe SM, Cunninghham J, Bommer J, et al. Long-term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCl. Nephrol Dial Transplant 2005; 20: 2186–93PubMedCrossRefGoogle Scholar
  75. 75.
    Indridason OS, Quarles LD, for the Durham Renal Osteodystrophy Study Group. Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Kidney Int 2000; 57: 282–92PubMedCrossRefGoogle Scholar
  76. 76.
    US FDA. Rocaltrol (calcitriol) oral solution and capsules [online]. Available from URL: http://www.fda.gov/cder/foi/nda/98/021068.htm [Accessed 2007 May 4]
  77. 77.
    Baker LRI, Abrams SML, Roe CJ, et al. 1,25(OH)2D3 administration in moderate renal failure: a prospective double-blind trial. Kidney Int 1989; 35: 661–9PubMedCrossRefGoogle Scholar
  78. 78.
    Acharya M, Andress D, Lunde N, et al. Safety experience of paricalcitol (Zemplar®) capsule in phase 3 trials in CKD stages 3 and 4 patients with secondary hyperparathyroidism (SHPT) [abstract no. SU-PO935]. 37th Annual Meeting & Scientific Exposition of the American Society of Nephrology; 2004 Oct 27–Nov 1; St Louis (MO)Google Scholar
  79. 79.
    Abboud H, Coyne D, Smolenski O, et al. A comparison of dosing regimens of paricalcitol capsule for the treatment of secondary hyperparathyroidism in CKD stages 3 and 4. Am J Nephrol 2006; 26(1): 105–14PubMedCrossRefGoogle Scholar
  80. 80.
    Charytan C, Coburn JW, Chonchol M, et al. Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis. Am J Kidney Dis 2005; 46: 58–67PubMedCrossRefGoogle Scholar
  81. 81.
    Hough TA, Bogani D, Cheeseman MT, et al. Activating calcium-sensing receptor mutation in the mouse is associated with cataracts and ectopic calcification. Proc Natl Acad Sci 2004; 101: 13566–71PubMedCrossRefGoogle Scholar
  82. 82.
    Alvarez-Hernandez D, Santamaria I, Rodriguez-Garcia M, et al. A novel mutation in the calcium-sensing receptor responsible for autosomal dominant hypocalcemia in a family with two uncommon parathyroid hormone polymorphisms. J Mol Endocrinol 2003;31: 255–62PubMedCrossRefGoogle Scholar
  83. 83.
    Messa P, Villa G, Braun J, et al. The OPTIMA study: lower doses of cinacalcet (Mimpara®/Sensipar®) are required to achieve KDOQI™ secondary hyperparathyroidism (HPT) targets in dialysis patients with less severe disease [abstract no. MP324]. XLIII European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress; 2006 Jul 15–18; GlasgowGoogle Scholar
  84. 84.
    Mitsopoulos E, Zanos S, Ginikopoulou E, et al. Initial dosing of paricalcitol based on PTH levels in hemodialysis patients with secondary hyperparathyroidism. Am J Kidney Dis 2006 Jul; 48(1): 114–21PubMedCrossRefGoogle Scholar
  85. 85.
    Ross EA, Kant KS, Melnick JZ, et al. Comparison of two dosing regimens of oral paricalcitol for secondary hyperparathyroidism (SHPT) in peritoneal dialysis (PD) patients [abstract no. TH-PO722]. American Society of Nephrology (ASN) 39th Renal Week Meeting; 2006 Nov 14–19; San Diego (CA)Google Scholar
  86. 86.
    Dobrez DG, Mathes A, Amdahl M, et al. Paricalcitol-treated patients experience improved hospitalization outcomes compared with calcitriol-treated patients in real-world clinical settings. Nephrol Dial Transplant 2004 May; 19(5): 1174–81PubMedCrossRefGoogle Scholar
  87. 87.
    Cunningham J, Danese M, Olson K, et al. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health-related quality of life in secondary hyperparathyroidism. Kidney Int 2005; 68: 1793–800PubMedCrossRefGoogle Scholar
  88. 88.
    Young EW, Albert JM, Akiba T, et al. Vitamin D therapy and mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS) [abstract no. TH-PO735]. J Am Soc Nephrol 2005; 16: 278AGoogle Scholar
  89. 89.
    Teng M, Wolf M, Lowrie E, et al. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 2003 Jul 31; 349(5): 446–56PubMedCrossRefGoogle Scholar
  90. 90.
    Kalantar-Zadeh K, Kuwae N, Regidor DL, et al. Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 2006; 70: 771–80PubMedCrossRefGoogle Scholar
  91. 91.
    Andress D. Nonclassical aspects of differential vitamin D receptor activation: implications for survival in patients with chronic kidney disease. Drugs 2007; 67(14): 1999–2012PubMedCrossRefGoogle Scholar

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

Personalised recommendations