Calcimimetics or vitamin D analogs for suppressing parathyroid hormone in end-stage renal disease: Time for a paradigm shift?

Nature Clinical Practice Nephrology

Volumn 5, Issue 1, 2009, Pages 24-33

  Wetmore, James B ^a,b   Quarles, L Darryl ^a  

^a UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^b UNIVERSITY OF KANSAS   (United States)

Author keywords

Calcimimetics; Calcium sensing receptor; Chronic kidney disease; Secondary hyperparathyroidism; Vitamin D

Indexed keywords

CALCIMIMETIC AGENT; CALCITRIOL; CALCIUM SENSING RECEPTOR; CINACALCET; FIBROBLAST GROWTH FACTOR 23; PARATHYROID HORMONE; PARICALCITOL; PLACEBO; VITAMIN D DERIVATIVE; VITAMIN D RECEPTOR;

CHRONIC KIDNEY DISEASE; CLINICAL TRIAL; DOSE RESPONSE; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG MECHANISM; HORMONE RELEASE; HUMAN; KIDNEY FAILURE; LOW DRUG DOSE; NONHUMAN; PARATHYROID FUNCTION; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; SECONDARY HYPERPARATHYROIDISM; VITAMIN D DEFICIENCY;

HUMANS; HYPERPARATHYROIDISM, SECONDARY; KIDNEY FAILURE, CHRONIC; NAPHTHALENES; PARATHYROID HORMONE; VITAMIN D;

EID: 57749208909     PISSN: 17458323     EISSN: 17458331     Source Type: Journal    
DOI: 10.1038/ncpneph0977     Document Type: Review

References (76)

1. Al-Badr W and Martin KJ (2008) Vitamin D and kidney disease. Clin J Am Soc Nephrol 3: 1555-1560
2. Brown AJ and Slatopolsky E (2007) Drug Insight: vitamin D analogs in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. Nat Clin Pract Endocrinol Metab 3: 134-144
3. Mehrotra R et al. (2008) Hypovitaminosis D in chronic kidney disease. Clin J Am Soc Nephrol 3: 1144-1151
4. Zehnder D et al. (2007) Cross-sectional analysis of abnormalities of mineral homeostasis, vitamin D and parathyroid hormone in a cohort of pre-dialysis patients. The chronic renal impairment in Birmingham (CRIB) study. Nephron Clin Pract 107: c109-c116
5. Slatopolsky E et al. (2001) Role of phosphorus in the pathogenesis of secondary hyperparathyroidism. Am J Kidney Dis 37: S54-S57
6. Rowe PS (2004) The wrickkened pathways of FGF23, MEPE and PHEX. Crit Rev Oral Biol Med 15: 264-281
7. +-dependent phosphate co-transport activity and 1alpha,25-dihydroxyvitamin D3 production. J Biol Chem 278: 2206-2211
8. Liu S et al. (2006) Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol 17: 1305-1315
9. Krajisnik T et al. (2007) Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol 195: 125-131
10. Shimada T et al. (2004) FGF-23 is a potent regulator of vitamin D metabolism and phosphate homeostasis. J Bone Miner Res 19: 429-435
11. Perwad F et al. (2007) Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1alpha-hydroxylase expression in vitro. Am J Physiol Renal Physiol 293: F1577-F1583
12. Larsson T et al. (2003) Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers. Kidney Int 64: 2272-2279
13. Gutierrez O et al. (2005) Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 16: 2205-2215
14. Shigematsu T et al. (2004) Possible involvement of circulating fibroblast growth factor 23 in the development of secondary hyperparathyroidism associated with renal insufficiency. Am J Kidney Dis 44: 250-256
15. Gutierrez OM et al. (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359: 584-592
16. Isakova T et al. (2008) Postprandial mineral metabolism and secondary hyperparathyroidism in early CKD. J Am Soc Nephrol 19: 615-623
17. Urakawa I et al. (2006) Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature 444: 770-774
18. Koh N et al. (2001) Severely reduced production of klotho in human chronic renal failure kidney. Biochem Biophys Res Commun 280: 1015-1020
19. Tokumoto M et al. (2005) Parathyroid cell growth in patients with advanced secondary hyperparathyroidism: vitamin D receptor, calcium sensing receptor, and cell cycle regulating factors. Ther Apher Dial 9 (Suppl 1): S27-S34
20. Portale AA et al. (1987) Dietary intake of phosphorus modulates the circadian rhythm in serum concentration of phosphorus. Implications for the renal production of 1,25-dihydroxyvitamin D. J Clin Invest 80: 1147-1154
21. Coburn JW et al. (2004) Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4. Am J Kidney Dis 43: 877-890
22. Tentori F et al. (2006) Mortality risk among hemodialysis patients receiving different vitamin D analogs. Kidney Int 70: 1858-1865
23. Messa P et al. (2008) The OPTIMA study: assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for secondary hyperparathyroidism. Clin J Am Soc Nephrol 3: 36-45
24. Block GA et al. (2004) Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 350: 1516-1525
25. Brown EM and MacLeod RJ (2001) Extracellular calcium sensing and extracellular calcium signaling. Physiol Rev 81: 239-297
26. Brown EM (2007) Clinical lessons from the calcium-sensing receptor. Nat Clin Pract Endocrinol Metab 3: 122-133
27. Silver J and Levi R (2005) Regulation of PTH synthesis and secretion relevant to the management of secondary hyperparathyroidism in chronic kidney disease. Kidney Int Suppl 95: S8-S12
28. Pollak MR et al. (1993) Mutations in the human Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Cell 75: 1297-1303
29. Ho C et al. (1995) A mouse model of human familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Nat Genet 11: 389-394
30. Li YC et al. (1998) Normalization of mineral ion homeostasis by dietary means prevents hyperparathyroidism, rickets, and osteomalacia, but not alopecia in vitamin D receptor-ablated mice. Endocrinology 139: 4391-4396
31. Drueke T et al. (2007) Can calcimimetics inhibit parathyroid hyperplasia? Evidence from preclinical studies. Nephrol Dial Transplant 22: 1828-1839
32. Goodman WG (2005) Calcimimetics: a remedy for all problems of excess parathyroid hormone activity in chronic kidney disease? Curr Opin Nephrol Hypertens 14: 355-360
33. Kos CH et al. (2003) The calcium-sensing receptor is required for normal calcium homeostasis independent of parathyroid hormone. J Clin Invest 111: 1021-1028
34. Tu Q et al. (2003) Rescue of the skeletal phenotype in CasR-deficient mice by transfer onto the Gcm2 null background. J Clin Invest 111: 1029-1037
35. Colloton M et al. (2005) Cinacalcet HCl attenuates parathyroid hyperplasia in a rat model of secondary hyperparathyroidism. Kidney Int 67: 467-476
36. Chin J et al. (2000) Activation of the calcium receptor by a calcimimetic compound halts the progression of secondary hyperparathyroidism in uremic rats. J Am Soc Nephrol 11: 903-911
37. de Francisco AL et al. (2008) Calcium-mediated parathyroid hormone release changes in patients treated with the calcimimetic agent cinacalcet. Nephrol Dial Transplant 23: 2895-2901
38. Lomonte C et al. (2008) Does vitamin D receptor and calcium receptor activation therapy play a role in the histopathologic alterations of parathyroid glands in refractory uremic hyperparathyroidism? Clin J Am Soc Nephrol 3: 794-799
39. Matsushita H et al. (1999) Proliferation of parathyroid cells negatively correlates with expression of parathyroid hormone-related protein in secondary parathyroid hyperplasia. Kidney Int 55: 130-138
40. Gogusev J et al. (1997) Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int 51: 328-336
41. 2+-sensing receptor in primary and uremic secondary hyperparathyroidism. J Clin Endocrinol Metab 81: 1598-1606
42. Brown AJ et al. (1999) Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: role of dietary phosphate. Kidney Int 55: 1284-1292
43. Ritter CS et al. (2001) Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor. Kidney Int 60: 1737-1744
44. Martin LN et al. (1998) Parathyroid glands in uraemic patients with refractory hyperparathyroidism: histopathology and p53 protein expression analysis. Histopathology 33: 46-51
45. Fukuda N et al. (1993) Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients. J Clin Invest 92: 1436-1443
46. Wang X et al. (2001) Vitamin D receptor and PCNA expression in severe parathyroid hyperplasia of uremic patients. Chin Med J (Engl) 114: 410-414
47. Tokumoto M et al. (2002) Reduced p21, p27 and vitamin D receptor in the nodular hyperplasia in patients with advanced secondary hyperparathyroidism. Kidney Int 62: 1196-1207
48. Yano S et al. (2003) Decrease in vitamin D receptor and calcium-sensing receptor in highly proliferative parathyroid adenomas. Eur J Endocrinol 148: 403-411
49. Maiti A and Beckman MJ (2007) Extracellular calcium is a direct effecter of VDR levels in proximal tubule epithelial cells that counter-balances effects of PTH on renal Vitamin D metabolism. J Steroid Biochem Mol Biol 103: 504-508
50. Brown AJ et al. (1996) Rat calcium-sensing receptor is regulated by vitamin D but not by calcium. Am J Physiol 270: F454-F460
51. Canaff L and Hendy GN (2002) Human calcium-sensing receptor gene: vitamin D response elements in promoters P1 and P2 confer transcriptional responsiveness to 1,25-dihydroxyvitamin D. J Biol Chem 277: 30337-30350
52. Fishbane S et al.: Cinacalcet HCl with low-dose vitamin D improves treatment of secondary hyperparathyroidism in dialysis patients versus vitamin D alone - the ACHIEVE study. Clin J Am Soc Nephrol, in press
53. Quarles LD et al. (2003) The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. J Am Soc Nephrol 14: 575-583
54. Lindberg JS et al. (2003) The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism. Kidney Int 63: 248-254
55. Strippoli GF et al. (2006) Meta-analysis of biochemical and patient-level effects of calcimimetic therapy. Am J Kidney Dis 47: 715-726
56. Fukagawa M et al. (2008) Cinacalcet (KRN1493) effectively decreases the serum intact PTH level with favorable control of the serum phosphorus and calcium levels in Japanese dialysis patients. Nephrol Dial Transplant 23: 328-335
57. Block GA et al. (2008) Combined therapy with cinacalcet and low doses of vitamin D sterols in patients with moderate to severe secondary hyperparathyroidism. Nephrol Dial Transplant 23: 2311-2318
58. Chertow GM et al. (2006) Cinacalcet hydrochloride (Sensipar) in hemodialysis patients on active vitamin D derivatives with controlled PTH and elevated calcium x phosphate. Clin J Am Soc Nephrol 1: 305-312
59. Martin KJ et al. (1998) 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 9: 1427-1432
60. Delmez JA et al. (2000) A controlled trial of the early treatment of secondary hyperparathyroidism with calcitriol in hemodialysis patients. Clin Nephrol 54: 301-308
61. Coyne DW et al. (2002) Differential effects of acute administration of 19-Nor-1,25-dihydroxy-vitamin D2 and 1,25-dihydroxy-vitamin D3 on serum calcium and phosphorus in hemodialysis patients. Am J Kidney Dis 40: 1283-1288
62. Joist HE et al. (2006) Differential effects of very high doses of doxercalciferol and paricalcitol on serum phosphorus in hemodialysis patients. Clin Nephrol 65: 335-341
63. Sprague SM et al. (2003) Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney Int 63: 1483-1490
64. Brandi L et al. (1992) Long-term suppression of secondary hyperparathyroidism by intravenous 1 alpha-hydroxyvitamin D3 in patients on chronic hemodialysis. Am J Nephrol 12: 311-318
65. Lindberg J et al. (2001) A long-term, multicenter study of the efficacy and safety of paricalcitol in end-stage renal disease. Clin Nephrol 56: 315-323
66. Akizawa T et al. (2002) Long-term effect of 1,25-dihydroxy-22- oxavitamin D(3) on secondary hyperparathyroidism in haemodialysis patients: one-year administration study. Nephrol Dial Transplant 17 (Suppl 10): S28-S36
67. Teng M et al. (2003) Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 349: 446-456
68. Teng M et al. (2005) Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol 16: 1115-1125
69. Kalantar-Zadeh K et al. (2006) Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 70: 771-780
70. Sprague SM et al. (2001) Suppression of parathyroid hormone secretion in hemodialysis patients: comparison of paricalcitol with calcitriol. Am J Kidney Dis 38: S51-S56
71. Block GA (1998) Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis 31: 607-617
72. Liu PT et al. (2006) Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311: 1770-1773
73. Bikle DD (2007) What is new in vitamin D: 2006-2007. Curr Opin Rheumatol 19: 383-388
74. Peterlik M and Cross HS (2005) Vitamin D and calcium deficits predispose for multiple chronic diseases. Eur J Clin Invest 35: 290-304
75. Andress D (2007) Nonclassical aspects of differential vitamin D receptor activation: implications for survival in patients with chronic kidney disease. Drugs 67: 1999-2012
76. Chertow GM et al. (2002) Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 62: 245-252