Clin Osteol 2012; 17(4): 150-159

Calcimimetics in the treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD): current knowledge, new information and future prospectsReview articles

S. Dusilová Sulková

Calcimimetics (cinacalcet hydrochloride) modulate the calcium-sensing receptor (CaR). The effect means not only suppression of pa­ rathormone secretion but also inhibition of parathyroid activity and growth. Since 2004 (a bit later in the C has been available for the treatment of secondary hyperparathyroidism (SHPT) in patients with kidney failure. Secondary hyperparathyroidism is a unifying moment of chronic kidney disease-mineral and bone disorder (CKD-MBD). The article is concerned with the effect of calcimimetics on individual CKD-MBD components (laboratory, bone and vascular). Large and long-term studies are available, including those from the actual clinical practice, documenting very good effectiveness in the tre­ atment of SHPT. They also have beneficial effects on hyperphosphatemia accompanying kidney failure. The effect on bones is likely; in the nearest future, results of a study assessing histomorphometry prior to and after one year of treatment should be published. Cinacalcet may slow the process of vascular calcification in di ents with full protection against vascular wall calcifications. As of now, cinacalcet has not been approved for the use in SHPT either prior to dialysis or after transplantation. Yet in these areas, data from controlled studies are available. Transplanted patients may benefit from concurrent decrease o increase of phosphate levels (hypophosphatemia treatment) but so far, the experiences have been limited. In the future, CaR is likely to be modulated in other organs, not only in the parathyroids. First reports have appeared on the deve­ lopment of third-generation calcimimetics with potentiated effects in other tissues and organs. Thus, t may be promising for other areas as well.

Keywords: secondary hyperparathyroidism, cinacalcet, calcium-sensing receptor, calcification, calciuria

Published: December 11, 2012  Show citation

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Dusilová Sulková S. Calcimimetics in the treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD): current knowledge, new information and future prospects. Osteologický bulletin. 2012;17(4):150-159.
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    References

    1. Block GA, Martin KJ, de Francisco ALM, Turner SA, Avram MM, Suranyi M, Hercz G, Cunningham J, Abu-Alfa AK, Messa P, Coyne DW, Locatelli F, Cohen RM, Evenepoel P, Moe SM, Fournier A, Braun J, McCary LC, Zani VJ, Olson KA, Drueke TB, Goodman WG. Cinacalcet hydrochloride for secondary hyper rathyroidism in patients receiving hemodialysis. N Engl J Med 2004;350: 1516-1525. Go to original source...
    2. Quarles LD, Sherrard DJ, Adler S, Rosansky SJ, McCary LC, Liu W, Turner Bushinsky DA The calcimimetic AMG073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. J Am Soc Nephrol 2003; 14: 575-583. Go to original source...
    3. Lindberg JS, Moe SM, Goodman WG, Coburn JW, Sprague SM, Liu W, Blaisdell PW, Brenner RM, Turner SA, Martin KJ. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and pe­ ritoneal dialysis patien Nephrol 2005;16:800-807.
    4. Moe S, Drueke T, Cunningham J, Goodman W, Martin K, Olgaard K, Moe S, Ott S, Sprague S, Lameire N, Eknoyan G. Kidney Disease. Improving Global Outcomes (KDIGO) et al. Definition, evaluation, and classification of dystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006;69:1945-1953. Go to original source...
    5. Amann K, Gross ML, London G, Ritz E. Hyperphosphataemia - a silent k patients with renal failure. Nephrol Dial Transplant 1999;14:2085-2087. Go to original source...
    6. London GM, Guerin AP, Marchais SJ et al. Arterial media calcification in end­ stage renal disease: impact on all Dial Transplant 2003;18:1731-1740. Go to original source...
    7. Braun J, Oldendorf M, Moshage W, Heidler R, Zeitler E, Luft FC. Electron beam computed tomography in the evaluation of card sis patients. Am J Kidney Dis 1996;27:394^01. Go to original source...
    8. Rodriguez M, Nemeth E, Martin D. The calcium-sensing receptor: a key facto the pathogenesis of secondary hyperparathyroidism. Am J Physiol Renal Physiol 2005; 288:F253-F264. Go to original source...
    9. Cunningham J, Locatelli F, Rodriguez M. Secondary hyperparathyroidism: pa genesis, disease progression, and therapeutic options. Clin J Am Soc Nephrol 2011;6:913-921. Go to original source...
    10. National Kidney Foundation. K/DOQI clinical practice guidelines for bone meta­ bolism a S1-S202.
    11. Drueke TB. Calcimimetics versus vitamin D. What are their relative roles? B Purif 2004;22:38-43. Go to original source...
    12. Brown EM, Gamba G, Richardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC. Cloning and characterization of an extracellu­ lar Ca2+ sensing receptor from bovine parathyroid. Nature 1993;366:575-580. Go to original source...
    13. Brown EM. Clinical utility of calcimimetics targe sensing receptor. Biochem Pharmacol 2010; 80:297-307. Go to original source...
    14. Nagano N. Pharmacological and clinical properties of calcimimetics: Calcium re­ ceptor activators that afford an innovative approach to controlling hyperparat idism. Pharmacol Ther 2006;109:339-365. Go to original source...
    15. Valle C, Rodriquez M, Santamaria R, Almaden Y, Rodriquez ME, Canadillas S, Martin-Malo A, Aljama P. Cinacalcet reduces the set point of the PTH-calcium curve. J Am Soc Nephrol 2008;19:2430-2436. Go to original source...
    16. Theman TA, Collins MT. The role of the calcium-sensing receptor in bone bio gy and pathophysiology. Curr Pharm Biotechnol 2009;10:289-301. Go to original source...
    17. Al-Aly Z. The new role of calcimimetics as vasculotropic agents. Kidney Int 2009;75:9-12. Go to original source...
    18. Bover J, Perez R, Molina M, Beavides B, Ariza F, Miguel JL, Tornero F, Torregrossa JV. Cinacalcet treatment for secondary hyperparathyroidism in dialy­ sis patients: an observational study in routine clinical practice. Nephron Clin Pr 2011;118:c109-c121. Go to original source...
    19. Zitt E, Rix M, Urena-Torres P, Fougue D, Jacobson SH, Ifetavy F, Dehmel B, Ryba M. Effectiveness of cinacalcet in patients with recurrent/persistent seconda­ ry hyperparathyroidism following parathyroidectomy: results of the ECHO study. Nephrol Dial Transplant 2011;26:1956-1961. Go to original source...
    20. Akizawa T, Kido R, Fukagawa M, Onishi Y, Yamaguchi T, Hasegawa T, Fukuhara S, Kurokawa K. Decreases in PTH in Japanese hemodialysis patiens with secon­ dary hyperparathyreoidism. Clin J Am Soc Nephrol 2011;6:2280-2288. Go to original source...
    21. Wetmore JB, Quarles DL. Calcimimetics or vitamin D analogs for suppressing pa­ rathyroid hormone in end-stage renal disease: time for a paradigma shift? Nature Clin Practice Nephrology 2009;5:24-32. Go to original source...
    22. Date T, Kawashita Y, Matsuzaki M, Kobayashi H, Nagano N. The administration of cinacalcet hydrochloride just before a haemodialysis session supresses the tran­ sient rise in intact parathyroid hormone induced by a low calcium dialysate: should cinacalcet hydrochloride be administered? Letter to editor. NDT Plus 2008;6:463-471. Go to original source...
    23. Schaefer RM, Bover J, Dellana F, Sanz D, Asensio C, Sanchez-Gonzalez MC, Gross P, Zani V, Carter D, Jehle PM. Efficacy of cinacalcet administered with first meal after dialysis: the SENSOR study. Clin Nephrol 2008;70:126-134. Go to original source...
    24. Borchhardt KA, Diarra D, Sulzbacher I. Benesch T, Haas M, SunderPlassmann G. Cinacalcet decreases bone formation rate in hypercalcemic hyper­ parathyroidism after kidney transplantation. Am J Nephrol 2010;31:482-489. Go to original source...
    25. Yajima A, Akizawa T, Tsukamoto Y, Kurihara S, Ito A Impact of cinacalcet drochloride on bone histology in patients with secondary hyperparathyroidism. Therap Apheresis and Dialysis 2008; 12 (Suppl.1):S38-S45. Go to original source...
    26. Malluche HH, Mawad H, Monieur-Faugere MC. Effects of treatment of r teodystrophy on bone histology. Clin J Am Soc Nephrol 2008;3:S157-S163. Go to original source...
    27. Regidor MJA Cinacalcet reduces vascular and soft tissue calcification in dary hyperparathyroidism (SHPT) in hemodialysis patients. Clin Nephrol 2009; 71:207-213.
    28. Urena-Torres PA, De Broe M. Calcium-sensing receptor, calcimimetics, and c diovascular calcifications in chronic kidney dinase. Kidney Int 2012;82:19-25. Go to original source...
    29. Floege J, Raggi P, Block GA, Urena-Torres P, Sciky B, Naso A, Nossuli K, Moustafa M, Goodman WG, Lopez N, Downey G, Dehmel B, Chertow G. Study design and subject baseline characteristics in the ADVANCE Study: effects of ci­ nacalcet on vascular cal plant 2010;25:1916-1923.
    30. Raggi P, Chertow GM, Urena-Torres P, Csiky B, Naso A, Nossuli K, Goodman WG, Lopez N, Downey G, Dehmel B, Floege J. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low-dose vitamin D on vascular calcif 2010;26:1327-1339. Go to original source...
    31. Urena-Torres P, Floege J, Hawley CM, Pedagogos E, Goodman WG, Pfetavy F, Reiner M, Raggi P. Protocol adherence and the progression of cardiovas calcification in the ADVANCE study. Nephrol Dial Transplant 2012; doi: 10.1093/ndt/gfs356. Go to original source...
    32. Drueke TB, Martin D, Rodriguez M. Can calcimimetics inhibic parathyroid perplasia? Evidence from preclinical studies. Nephrol Dial Transplant 2007; 22:1828-1839. Go to original source...
    33. Komaba H, Nakanishi S, Fujimori A, Tanaka M, Shin J, Shibuya K, Nishiok Hasegawa H, Kurosawa T, Fukagawa M. Cinacalcet effectively reduces parathy­ roid hormone secretion and gland volume regardless of pretreatment gland si patients with secondary hyperparathyroidism. Clin J Am Soc Nephrol 2010; 5:2305-2314. Go to original source...
    34. Ichii M, Ishimura E, Okuno S, Chou H, Kato Y, Tsuboniwa N, Nagasue K, Maekawa K, Yamakawa T, Inaba M, Nishizawa Y. Decreases in parathyroid gland volume after cinacalcet treatment in hemodialysis pati parathyroidism. Nephron Clin Pract 2010;115:c195-c202. Go to original source...
    35. Weisinger JR, Carlini RG, Rojas E, Bellorin-Font E. transplantation. Clin J Am Soc Nephrol 2006;1:1300-1313. Go to original source...
    36. Sprague SM, Belozeroff V, Danese M, Martin LP, Olgaard K. Abnormal bo mineral metabolism in kidney transplant patients - a review. Am J Nephrol 2008;28:246-253. Go to original source...
    37. Ambrus C, Molnar MZ, Czira ME, Rosivall L, Kiss I, Remport A, Szathmari M, Musci I. Calcium, phosphate and parathyroid metabolism in kidney transpl patients. Int Urol Nephrol 2009;41:1029-1038. Go to original source...
    38. Evenepoel P, Claes K, Kuypers D, Maes B, Bammens B, Vanrenterghem Y. Natural history ofparathyroid function and calcium metabolism after kidney tr plantation: a single centre study. Nephrol Dial Transplant 2004;19:1281-1287. Go to original source...
    39. Gwinner W, Suppa S, Mengel M, Hov L, Kreipe HH, Haller H, Schwarz A Early calcification of renal allografts detected by protocol biopsies: causes and cli implications. Am J Transplant 2005;5:1934-1941. Go to original source...
    40. Serra AL, Braun SC, Starke A, Savoca R, Harsberger M, RussmannS, Corti N, Wthrich RP. Pharmacokinetics and pharmacodynamics of cinacalcet in patiens with hyperparathyroidism after renal transplantation. Am J Transplant 2008; 8:803-810. Go to original source...
    41. Falck P, Vethe NT, Asberg A, Midtvedt K, Bergan S, Reubsaet JL, Holdaas H. Cinacalcet's effect on the pharmacokinetics of tacrolimus, cyclosporine and mycophenolate in renal transplant recipients. Nephrol Dial Transplant 2008;23: 1048-1053. Go to original source...
    42. Bhan I, Shah A, Holmes J, Isakova T, Gutierrez O, Burnett SA, Juppner H, Wolf M. Post-transplant hypophosphatemia: tertiary hyperphosphatoninism? Kidney Int 2006;70:1486-1494. Go to original source...
    43. Trombetti A, Richert L, Hadaya K, Graf JD, Herrmann FR, Ferrari SL, Martin PY, Rizzoli R. Early post-transplantation hypophosphatemi ted FGF-23 levels. Eur J Endocrinol 2011;164:839-847. Go to original source...
    44. Serra AL, Wurhmann C, Wuthrich RP. Phosphatemic effect of cinacalcet in kid­ ney transplant rec 2008;52:1151-1157.
    45. Morales E, Gutierrez E, Andres A Treatment with calcimimetics in kidney tr plantation. Transplantation Reviews 2010;24:79-88. Go to original source...
    46. Serra A, Schwarz AA, Wick FH, Marti HP, Wurthrich RP. Successful treatment of hypercalcemia with cinacalcet in renal transplant recipien perparathyroidism. Nephrol Dial Transplant 2005;20:1315-1319. Go to original source...
    47. Cohen JB, Gordon CE, Balk EM, Francis JM. Cinacalcet for the treatment of hy­ perparathyroidism in kidney transplant recipients: a systematic review and me analysis. Transplantation 2012;94:1041-1048. Go to original source...
    48. Charytan Ch, Coburn JW, Chonchol M, Herman J, Lien YH, Liu W, Klassen PS, McCary LC, Pichette V. Cinacalcet hydrochloride is an effective treatment for condary hyperparathyroidism in patients with CKD not receiving dialysis. Am J Kidney Dis 2005;46:58-67. Go to original source...
    49. Chonchol M, Locatelli F, Abboud JE, Charytan C, de Francisco AL, Jolly S, Kaplan M, Roger SD, Sarkar S, Albizem MB, Mix TC, Kubo Y, Block GA A ran­ domized, double blind, placebo-controlled study to assess the efficacy and saf of cinacalcet HCl in participants with CKD not receiving dialysis. Am J Kidney Dis 2009;53:197-207. Go to original source...
    50. Cannata-Andia JB, Fernandez-Martin JL. Should cinacalce who are not on dialysis? Nat Rev Nephrol 2009;5(6):307-308. Go to original source...
    51. de Francisco ALM, Pinera C, Palomar R. Cinacalcet should be used to trea condary hyperparathyroidism in stage 3-4 chronic kidney disease. Nature Clin Pract Nephrol 2008;4:266-267. Go to original source...
    52. Coyne DW. Cinacalcet should not be used to treat secondary hyperparathyroi in stage 3-4 chronic kidney disease. Nature Clin Pract Nephrol 2008;4:264-265. Go to original source...
    53. Cunningham J, Danesh M, Olson K, Klassen P, Chertow GM. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture and health-related quality of life in secondary hyperparathyroidism. Kidney Int 2005;68:1793-1800. Go to original source...
    54. Block GA, Zaun D, Smits G, Persky M, Brilhart S, Nieman K, Liu J, St Peter Cinacalcet hydrochloride treatment significantly improves all-cause and cardio­ vascular 578-589.
    55. The EVOLVE Trial Investigators: The effect of cinacalcet on cardiovascular dise in patiens undergoing dialysis. N Engl J Med 2012; doi 10.1056/NEJMoal205624. Go to original source...
    56. Muscheites J, Wigger M, Drueckler E, Fisher DC, Kundt G, Haffner D. Cinacalcet for secondary hyperparathyroidism in children with end-stage renal disease. Ibdiatr Nephrol 2008;23:1823-1829. Go to original source...
    57. Messa P, Castelnovo C, Scalamogna A Calcimimetics in peritoneal dialysis pati­ ents. Contrib Nephrol 2012;178:143-149. Go to original source...
    58. Mohammed IA, Sekar V, Bubtana AJ, Mitra S, Hutchison AJ. Proximal calciphylaxis treated with calcimimetic 'cinacalcet'. Nephrol Dial Transplant 2008;23: 387-389. Go to original source...
    59. Scola N, Gackler D, Stucker M, Kreuter A Complete clearance of calciphylaxis following combined treatment with cinacalcet and sodium thiosulphate. J Germ Soc Dermatol 2011;9:1030-1031. Go to original source...
    60. Švára F. Potenciální nové a méně časté indikace cinacalcetu. Osteol Bulletin 2010;15:144-147.
    61. Ketteler M, Martin KJ, Wolf M, Amdahl M, Cozzolino M, Goldsmith D, Sharma A, Marx S, Khan S. Pricalcitol versus cinacalcet plus low-dose vitamin D thera­ py for the treatment of secondary hyperparathyroidism in patients receiving hae­ modialysis: results ofthe IMPACT SHPT study. Nephrol Dial Transplant 2012;27: 3270-3278. Go to original source...
    62. Messa P, Macário F, Yaqoob M, Bouman K, Braun J, von Albertini B, Brink H, Maduell F, Graf H, Frazäo JM, Bos WJ, Torregrosa V, Saha H, Reichel H, Wilkie M, Zani VJ, Molemans B, Carter D, Locatelli F. The OPTIMA study: assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for secondary hyperpa­ rathyroidism. Clin J Am Soc Nephrol 2008;3:36-45. Go to original source...
    63. Fishbane S, Shapiro WB, Corry DB, Vicks SL, Roppolo M, Rappaport K, Ling X, Goodman WG, Turner S, Charytan C. 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 2008;3: 1718-1725. Go to original source...
    64. Evenepoel P. Calcimimetics in chronic kidney disease: evidence, opportunities and challenges. Kidney Int 2008;74:265-275. Go to original source...
    65. Zitt E, Woess E, Mayer G, Lhotta K. Effect of cinacalcet on renal electrolyte handling and systemic arterial blood pressure in kidney transplant patients with persistent hyperparathyroidism. Transplantation 2011; doi: 10.1097/TP.ObO13822d87e8. Go to original source...
    66. Gattone 2nd VH, Chen NX, Sinders RM, Seifert RM, Duan M, Martin D et al. Calcimimetics inhibit late stage cyst growth in ADPKD. J Am Soc Nephrol 2009;20:1527-1532. Go to original source...
    67. Oh J, Beckmann J, Bloch J, Hettgen V, Mueller J, Li L, Hoemme M, Gross ML, Penzel R, Mundel P, Schaefer F, Schmitt CP. Stimulation of the calcium-sensing receptor stabilizes the podocyte cytoskeleton, improves cell survival, and reduces toxin-induced glomerulosclerosis. Kidney Int 2011; doi:10.1038/ki2011.105. Go to original source...
    68. Henley C 3rd, Yang Y, Davis J, Lu JY, Morony S, Fan W, Florio M, Sun B, Shatzen E, Pretorius JK, Richards WG, St Jean DJ Jr, Fotsch C, Reagan JD. Discovery of a calcimimetic with differential effects on parathyroid hormone and calcitonin secretion. J Pharmacol Exp Ther 2011;337:681-691. Go to original source...

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