Pediatric Nephrology

, Volume 25, Issue 4, pp 609–616

New therapies: calcimimetics, phosphate binders and vitamin D receptor activators

  • Jorge B. Cannata-Andía
  • Minerva Rodriguez-García
  • Pablo Román-García
  • Diego Tuñón-le Poultel
  • Francisco López-Hernández
  • Diego Rodríguez-Puyol
Review
  • 387 Downloads

Abstract

At present, new compounds are available to treat secondary hyperparathyroidism, namely calcimimetics, novel phosphorus binders and also novel vitamin D receptor activators. Calcimimetics increase the sensitivity of the parathyroid gland to calcium through spatial configurational changes of the calcium-sensing receptor. In addition, experimental studies have demonstrated that calcimimetics also upregulate both the calcium-sensing receptor and the vitamin D receptor. They are efficacious in children, though the experience in paediatric chronic kidney disease is still limited. Sevelamer, lanthanum carbonate and magnesium iron hydroxycarbonate are novel phosphorus binders available on the market. Several studies have demonstrated their efficacy and safety up to 6 years, though costs are the main limitation for a wider use. Since almost all the experience available on the new phosphorus binders comes from its use in adults, studies on children are needed in order to confirm the efficacy and safety of these products. Other new salts and polymers are also being developed. New vitamin D receptor activators, such as paricalcitol, are as effective at suppressing parathyroid hormone (PTH) as the traditional vitamin D receptor activators used for the past two decades, but they have a better and safer profile, showing fewer calcaemic and phosphoraemic effects while preserving the desirable effects of the vitamin D receptor activators on the cardiovascular system, hypertension, inflammation and fibrosis. Their use in children with chronic kidney disease has revealed similar responses to those of adults. The novel compounds discussed in this review should facilitate and improve the management of mineral and bone disorders in children with chronic kidney disease.

Keywords

Calcimimetics Vitamin D receptor activator (VDRA) Phosphorus binder Chronic kidney disease-related mineral and bone disorders (CKD-MBDs) Children 

References

  1. 1.
    Locatelli F, Cannata-Andia JB, Drueke TB, Horl WH, Fouque D, Heimburger O, Ritz E (2002) Management of disturbances of calcium and phosphate metabolism in chronic renal insufficiency, with emphasis on the control of hyperphosphataemia. Nephrol Dial Transplant 17:723–731CrossRefPubMedGoogle Scholar
  2. 2.
    Cannata-Andia JB, Carrera F (2008) The pathophysiology of secondary hyperparathyroidism and the consequences of uncontrolled mineral metabolism in chronic kidney disease: the role of COSMOS. Nephrol Dial Transplant Plus 1:i2–i6Google Scholar
  3. 3.
    Levin A, Bakris GL, Molitch M, Smulders M, Tian J, Williams LA, Andress DL (2007) Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 71:31–38CrossRefPubMedGoogle Scholar
  4. 4.
    Martinez I, Saracho R, Montenegro J, Llach F (1997) The importance of dietary calcium and phosphorous in the secondary hyperparathyroidism of patients with early renal failure. Am J Kidney Dis 29:496–502CrossRefPubMedGoogle Scholar
  5. 5.
    Block GA, Klassen PS, Lazarus JM, Ofsthun N, Lowrie EG, Chertow GM (2004) Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15:2208–2218CrossRefPubMedGoogle Scholar
  6. 6.
    Tentori F, Blayney MJ, Albert JM, Gillespie BW, Kerr PG, Bommer J, Young EW, Akizawa T, Akiba T, Pisoni RL, Robinson BM, Port FK (2008) Mortality risk for dialysis patients with different levels of serum calcium, phosphorus, and PTH: the Dialysis Outcomes and Practice Patterns Study (DOPPS). Am J Kidney Dis 52:519–530CrossRefPubMedGoogle Scholar
  7. 7.
    Carrillo-Lopez N, Alvarez-Hernandez D, Gonzalez-Suarez I, Roman-Garcia P, Valdivielso JM, Fernandez-Martin JL, Cannata-Andia JB (2008) Simultaneous changes in the calcium-sensing receptor and the vitamin D receptor under the influence of calcium and calcitriol. Nephrol Dial Transplant 23:3479–3484CrossRefPubMedGoogle Scholar
  8. 8.
    Carrillo-Lopez N, Fernandez-Martin JL, Cannata-Andia JB (2009) The role of calcium, calcitriol and its receptors in parathyroid regulation. Nefrologia 29:103–108PubMedGoogle Scholar
  9. 9.
    Juppner H, Brown EM, Kronenberg HM (1999) Parathyroid hormone. In: Favus M (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 4th edn. Lippincott Williams & Wilkins, Philadelphia, pp 80–87Google Scholar
  10. 10.
    Silver J, Kilav R, Naveh-Many T (2002) Mechanisms of secondary hyperparathyroidism. Am J Physiol Renal Physiol 283:F367–F376PubMedGoogle Scholar
  11. 11.
    Brown EM, Gamba G, Riccardi D, Lombardi M, Butters R, Kifor O, Sun A, Hediger MA, Lytton J, Hebert SC (1993) Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid. Nature 366:575–580CrossRefPubMedGoogle Scholar
  12. 12.
    Brown AJ, Zhong M, Ritter C, Brown EM, Slatopolsky E (1995) Loss of calcium responsiveness in cultured bovine parathyroid cells is associated with decreased calcium receptor expression. Biochem Biophys Res Commun 212:861–867CrossRefPubMedGoogle Scholar
  13. 13.
    Brown EM (2000) Calcium receptor and regulation of parathyroid hormone secretion. Rev Endocr Metab Disord 1:307–315CrossRefPubMedGoogle Scholar
  14. 14.
    Naveh-Many T, Marx R, Keshet E, Pike JW, Silver J (1990) Regulation of 1,25-dihydroxyvitamin D3 receptor gene expression by 1,25-dihydroxyvitamin D3 in the parathyroid in vivo. J Clin Invest 86:1968–1975CrossRefPubMedGoogle Scholar
  15. 15.
    Naveh-Many T, Rahamimov R, Livni N, Silver J (1995) Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D. J Clin Invest 96:1786–1793CrossRefPubMedGoogle Scholar
  16. 16.
    Mizobuchi M, Hatamura I, Ogata H, Saji F, Uda S, Shiizaki K, Sakaguchi T, Negi S, Kinugasa E, Koshikawa S, Akizawa T (2004) Calcimimetic compound upregulates decreased calcium-sensing receptor expression level in parathyroid glands of rats with chronic renal insufficiency. J Am Soc Nephrol 15:2579–2587CrossRefPubMedGoogle Scholar
  17. 17.
    Rodriguez ME, Almaden Y, Canadillas S, Canalejo A, Siendones E, Lopez I, Aguilera-Tejero E, Martin D, Rodriguez M (2007) The calcimimetic R-568 increases vitamin D receptor expression in rat parathyroid glands. Am J Physiol Renal Physiol 292:F1390–F1395CrossRefPubMedGoogle Scholar
  18. 18.
    Meola M, Petrucci I, Barsotti G (2009) Long-term treatment with cinacalcet and conventional therapy reduces parathyroid hyperplasia in severe secondary hyperparathyroidism. Nephrol Dial Transplant 24:982–989CrossRefPubMedGoogle Scholar
  19. 19.
    Miller MA, Fox J (2000) Daily transient decreases in plasma parathyroid hormone levels induced by the calcimimetic NPS R-568 slows the rate of bone loss but does not increase bone mass in ovariectomized rats. Bone 27:511–519CrossRefPubMedGoogle Scholar
  20. 20.
    Ishii H, Wada M, Furuya Y, Nagano N, Nemeth EF, Fox J (2000) Daily intermittent decreases in serum levels of parathyroid hormone have an anabolic-like action on the bones of uremic rats with low-turnover bone and osteomalacia. Bone 26:175–182CrossRefPubMedGoogle Scholar
  21. 21.
    Block GA, Martin KJ, de Francisco AL, Turner SA, Avram MM, Suranyi MG, 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 (2004) Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 350:1516–1525CrossRefPubMedGoogle Scholar
  22. 22.
    Block GA, Zeig S, Sugihara J, Chertow GM, Chi EM, Turner SA, Bushinsky DA (2008) Combined therapy with cinacalcet and low doses of vitamin D sterols in patients with moderate to severe secondary hyperparathyroidism. Nephrol Dial Transplant 23:2311–2318CrossRefPubMedGoogle Scholar
  23. 23.
    Bencova V, Malberti F, Ashman N (2009) “Real-world” use of cinacalcet in the management of SHPT among European countries. World Congress of Nephrology, Milan, May 2009. Abstract SU577Google Scholar
  24. 24.
    Chertow GM, Pupim LB, Block GA, Correa-Rotter R, Drueke TB, Floege J, Goodman WG, London GM, Mahaffey KW, Moe SM, Wheeler DC, Albizem M, Olson K, Klassen P, Parfrey P (2007) Evaluation of cinacalcet therapy to lower cardiovascular events (EVOLVE): rationale and design overview. Clin J Am Soc Nephrol 2:898–905CrossRefPubMedGoogle Scholar
  25. 25.
    Chonchol M, Locatelli F, Abboud HE, Charytan C, de Francisco AL, Jolly S, Kaplan M, Roger SD, Sarkar S, Albizem MB, Mix TC, Kubo Y, Block GA (2009) A randomized, double-blind, placebo-controlled study to assess the efficacy and safety of cinacalcet HCl in participants with CKD not receiving dialysis. Am J Kidney Dis 53:197–207CrossRefPubMedGoogle Scholar
  26. 26.
    Cannata-Andia JB, Fernandez-Martin JL (2009) Mineral metabolism: should cinacalcet be used in patients who are not on dialysis? Nat Rev Nephrol 5:307–308CrossRefPubMedGoogle Scholar
  27. 27.
    Silverstein DM, Kher KK, Moudgil A, Khurana M, Wilcox J, Moylan K (2008) Cinacalcet is efficacious in pediatric dialysis patients. Pediatr Nephrol 23:1817–1822CrossRefPubMedGoogle Scholar
  28. 28.
    Muscheites J, Wigger M, Drueckler E, Fischer DC, Kundt G, Haffner D (2008) Cinacalcet for secondary hyperparathyroidism in children with end-stage renal disease. Pediatr Nephrol 23:1823–1829CrossRefPubMedGoogle Scholar
  29. 29.
    Nakagawa K, Perez EC, Oh J, Santos F, Geldyyev A, Gross ML, Schaefer F, Schmitt CP (2008) Cinacalcet does not affect longitudinal growth but increases body weight gain in experimental uraemia. Nephrol Dial Transplant 23:2761–2767CrossRefPubMedGoogle Scholar
  30. 30.
    EMEA (2001) European assessment report mimpara. European Medicines AgencyGoogle Scholar
  31. 31.
    Slatopolsky E, Finch J, Denda M, Ritter C, Zhong M, Dusso A, MacDonald PN, Brown AJ (1996) Phosphorus restriction prevents parathyroid gland growth. High phosphorus directly stimulates PTH secretion in vitro. J Clin Invest 97:2534–2540CrossRefPubMedGoogle Scholar
  32. 32.
    Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ, Proudfoot D, Jahnen-Dechent W, Weissberg PL, Shanahan CM (2004) Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. J Am Soc Nephrol 15:2857–2867CrossRefPubMedGoogle Scholar
  33. 33.
    Guerin AP, Blacher J, Pannier B, Marchais SJ, Safar ME, London GM (2001) Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure. Circulation 103:987–992PubMedGoogle Scholar
  34. 34.
    Isakova T, Gutierrez OM, Chang Y, Shah A, Tamez H, Smith K, Thadhani R, Wolf M (2009) Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol 20:388–396CrossRefPubMedGoogle Scholar
  35. 35.
    Cannata-Andia JB, Naves-Diaz M (2009) Phosphorus and survival: key questions that need answers. J Am Soc Nephrol 20:234–236CrossRefPubMedGoogle Scholar
  36. 36.
    Gutierrez OM, Mannstadt M, Isakova T, Rauh-Hain JA, Tamez H, Shah A, Smith K, Lee H, Thadhani R, Juppner H, Wolf M (2008) Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med 359:584–592CrossRefPubMedGoogle Scholar
  37. 37.
    Slatopolsky E, Brown A, Dusso A (1999) Pathogenesis of secondary hyperparathyroidism. Kidney Int Suppl 73:S14–S19CrossRefPubMedGoogle Scholar
  38. 38.
    Slatopolsky E, Dusso A, Brown AJ (1999) The role of phosphorus in the development of secondary hyperparathyroidism and parathyroid cell proliferation in chronic renal failure. Am J Med Sci 317:370–376CrossRefPubMedGoogle Scholar
  39. 39.
    Goodman WG, Goldin J, Kuizon BD, Yoon C, Gales B, Sider D, Wang Y, Chung J, Emerick A, Greaser L, Elashoff RM, Salusky IB (2000) Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342:1478–1483CrossRefPubMedGoogle Scholar
  40. 40.
    Cannata-Andia JB, Fernandez-Martin JL (2002) The clinical impact of aluminium overload in renal failure. Nephrol Dial Transplant 17(Suppl 2):9–12PubMedGoogle Scholar
  41. 41.
    London G, Marchais S, Guerin A, Metivier F (2007) Arterial hypertension, chronic renal insufficiency and dialysis. Nephrol Ther 3(Suppl 3):S156–S161PubMedGoogle Scholar
  42. 42.
    Hutchison AJ (2009) Oral phosphate binders. Kidney Int 75:906–914CrossRefPubMedGoogle Scholar
  43. 43.
    Chertow GM, Burke SK, Raggi P (2002) Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 62:245–252CrossRefPubMedGoogle Scholar
  44. 44.
    Ferramosca E, Burke S, Chasan-Taber S, Ratti C, Chertow GM, Raggi P (2005) Potential antiatherogenic and anti-inflammatory properties of sevelamer in maintenance hemodialysis patients. Am Heart J 149:820–825CrossRefPubMedGoogle Scholar
  45. 45.
    Garg JP, Chasan-Taber S, Blair A, Plone M, Bommer J, Raggi P, Chertow GM (2005) Effects of sevelamer and calcium-based phosphate binders on uric acid concentrations in patients undergoing hemodialysis: a randomized clinical trial. Arthritis Rheum 52:290–295CrossRefPubMedGoogle Scholar
  46. 46.
    Damment SJ, Pennick M (2007) Systemic lanthanum is excreted in the bile of rats. Toxicol Lett 171:69–77CrossRefPubMedGoogle Scholar
  47. 47.
    Hutchison AJ, Maes B, Vanwalleghem J, Asmus G, Mohamed E, Schmieder R, Backs W, Jamar R, Vosskuhler A (2005) Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate. Nephron Clin Pract 100:c8–c19CrossRefPubMedGoogle Scholar
  48. 48.
    Hutchison AJ, Laville M (2008) Switching to lanthanum carbonate monotherapy provides effective phosphate control with a low tablet burden. Nephrol Dial Transplant 23:3677–3684CrossRefPubMedGoogle Scholar
  49. 49.
    Drueke TB (2007) Lanthanum carbonate as a first-line phosphate binder: the “cons”. Semin Dial 20:329–332CrossRefPubMedGoogle Scholar
  50. 50.
    Hutchison AJ, Barnett ME, Krause R, Kwan JT, Siami GA (2008) Long-term efficacy and safety profile of lanthanum carbonate: results for up to 6 years of treatment. Nephron Clin Pract 110:c15–c23CrossRefPubMedGoogle Scholar
  51. 51.
    Spasovski GB, Sikole A, Gelev S, Masin-Spasovska J, Freemont T, Webster I, Gill M, Jones C, De Broe ME, D’Haese PC (2006) Evolution of bone and plasma concentration of lanthanum in dialysis patients before, during 1 year of treatment with lanthanum carbonate and after 2 years of follow-up. Nephrol Dial Transplant 21:2217–2224CrossRefPubMedGoogle Scholar
  52. 52.
    McIntyre CW (2007) New developments in the management of hyperphosphatemia in chronic kidney disease. Semin Dial 20:337–341CrossRefPubMedGoogle Scholar
  53. 53.
    Meema HE, Oreopoulos DG, Rapoport A (1987) Serum magnesium level and arterial calcification in end-stage renal disease. Kidney Int 32:388–394CrossRefPubMedGoogle Scholar
  54. 54.
    Navarro JF, Macia ML, Gallego E, Mendez ML, Chahin J, Garcia-Nieto V, Garcia JJ (1997) Serum magnesium concentration and PTH levels. Is long-term chronic hypermagnesemia a risk factor for adynamic bone disease? Scand J Urol Nephrol 31:275–280CrossRefPubMedGoogle Scholar
  55. 55.
    Salusky IB, Goodman WG, Sahney S, Gales B, Perilloux A, Wang HJ, Elashoff RM, Juppner H (2005) Sevelamer controls parathyroid hormone-induced bone disease as efficiently as calcium carbonate without increasing serum calcium levels during therapy with active vitamin D sterols. J Am Soc Nephrol 16:2501–2508CrossRefPubMedGoogle Scholar
  56. 56.
    Valdivielso JM, Cannata Andía JB, Fernández E (2009) A new role for the vitamin D receptor activation (VDRA) in chronic kidney disease. Am J Physiol Renal Physiol 297:F1502–F1509CrossRefPubMedGoogle Scholar
  57. 57.
    Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R (2003) Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med 349:446–456CrossRefPubMedGoogle Scholar
  58. 58.
    Wolf M, Shah A, Gutierrez O, Ankers E, Monroy M, Tamez H, Steele D, Chang Y, Camargo CA Jr, Tonelli M, Thadhani R (2007) Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 72:1004–1013CrossRefPubMedGoogle Scholar
  59. 59.
    Shoji T, Shinohara K, Kimoto E, Emoto M, Tahara H, Koyama H, Inaba M, Fukumoto S, Ishimura E, Miki T, Tabata T, Nishizawa Y (2004) Lower risk for cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users in a haemodialysis population. Nephrol Dial Transplant 19:179–184CrossRefPubMedGoogle Scholar
  60. 60.
    Tentori F, Hunt WC, Stidley CA, Rohrscheib MR, Bedrick EJ, Meyer KB, Johnson HK, Zager PG (2006) Mortality risk among hemodialysis patients receiving different vitamin D analogs. Kidney Int 70:1858–1865CrossRefPubMedGoogle Scholar
  61. 61.
    Naves-Diaz M, Alvarez-Hernandez D, Passlick-Deetjen J, Guinsburg A, Marelli C, Rodriguez-Puyol D, Cannata-Andia JB (2008) Oral active vitamin D is associated with improved survival in hemodialysis patients. Kidney Int 74:1070–1078CrossRefPubMedGoogle Scholar
  62. 62.
    Xiang W, Kong J, Chen S, Cao LP, Qiao G, Zheng W, Liu W, Li X, Gardner DG, Li YC (2005) Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab 288:E125–E132CrossRefPubMedGoogle Scholar
  63. 63.
    Tishkoff DX, Nibbelink KA, Holmberg KH, Dandu L, Simpson RU (2008) Functional vitamin D receptor (VDR) in the t-tubules of cardiac myocytes: VDR knockout cardiomyocyte contractility. Endocrinology 149:558–564CrossRefPubMedGoogle Scholar
  64. 64.
    O’Connell TD, Berry JE, Jarvis AK, Somerman MJ, Simpson RU (1997) 1, 25- Dihydroxyvitamin D3 regulation of cardiac myocyte proliferation and hypertrophy. Am J Physiol 272:H1751–H1758PubMedGoogle Scholar
  65. 65.
    Walters MR, Ilenchuk TT, Claycomb WC (1987) 1, 25-Dihydroxyvitamin D3 stimulates 45Ca2+ uptake by cultured adult rat ventricular cardiac muscle cells. J Biol Chem 262:2536–2541PubMedGoogle Scholar
  66. 66.
    Rahman A, Hershey S, Ahmed S, Nibbelink K, Simpson RU (2007) Heart extracellular matrix gene expression profile in the vitamin D receptor knockout mice. J Steroid Biochem Mol Biol 103:416–419CrossRefPubMedGoogle Scholar
  67. 67.
    Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D’Agostino RB, Wolf M, Vasan RS (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117:503–511CrossRefPubMedGoogle Scholar
  68. 68.
    Ravani P, Malberti F, Tripepi G, Pecchini P, Cutrupi S, Pizzini P, Mallamaci F, Zoccali C (2009) Vitamin D levels and patient outcome in chronic kidney disease. Kidney Int 75:88–95CrossRefPubMedGoogle Scholar
  69. 69.
    Bodyak N, Ayus JC, Achinger S, Shivalingappa V, Ke Q, Chen YS, Rigor DL, Stillman I, Tamez H, Kroeger PE, Wu-Wong RR, Karumanchi SA, Thadhani R, Kang PM (2007) Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals. Proc Natl Acad Sci U S A 104:16810–16815CrossRefPubMedGoogle Scholar
  70. 70.
    Fryer RM, Rakestraw PA, Nakane M, Dixon D, Banfor PN, Koch KA, Wu-Wong JR, Reinhart GA (2007) Differential inhibition of renin mRNA expression by paricalcitol and calcitriol in C57/BL6 mice. Nephron Physiol 106:p76–p81CrossRefPubMedGoogle Scholar
  71. 71.
    Cardus A, Panizo S, Parisi E, Fernandez E, Valdivielso JM (2007) Differential effects of vitamin D analogs on vascular calcification. J Bone Miner Res 22:860–866CrossRefPubMedGoogle Scholar
  72. 72.
    Shroff R, Egerton M, Bridel M, Shah V, Donald AE, Cole TJ, Hiorns MP, Deanfield JE, Rees L (2008) A bimodal association of vitamin D levels and vascular disease in children on dialysis. J Am Soc Nephrol 19:1239–1246CrossRefPubMedGoogle Scholar
  73. 73.
    Timms PM, Mannan N, Hitman GA, Noonan K, Mills PG, Syndercombe-Court D, Aganna E, Price CP, Boucher BJ (2002) Circulating MMP9, vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM 95:787–796CrossRefPubMedGoogle Scholar
  74. 74.
    Hintzpeter B, Mensink GB, Thierfelder W, Muller MJ, Scheidt-Nave C (2008) Vitamin D status and health correlates among German adults. Eur J Clin Nutr 62:1079–1089CrossRefPubMedGoogle Scholar
  75. 75.
    Tan X, Li Y, Liu Y (2006) Paricalcitol attenuates renal interstitial fibrosis in obstructive nephropathy. J Am Soc Nephrol 17:3382–3393CrossRefPubMedGoogle Scholar
  76. 76.
    Agarwal R, Acharya M, Tian J, Hippensteel RL, Melnick JZ, Qiu P, Williams L, Batlle D (2005) Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int 68:2823–2828CrossRefPubMedGoogle Scholar
  77. 77.
    Alborzi P, Patel NA, Peterson C, Bills JE, Bekele DM, Bunaye Z, Light RP, Agarwal R (2008) Paricalcitol reduces albuminuria and inflammation in chronic kidney disease: a randomized double-blind pilot trial. Hypertension 52:249–255CrossRefPubMedGoogle Scholar
  78. 78.
    Zhang Z, Zhang Y, Ning G, Deb DK, Kong J, Li YC (2008) Combination therapy with AT1 blocker and vitamin D analog markedly ameliorates diabetic nephropathy: blockade of compensatory renin increase. Proc Natl Acad Sci U S A 105:15896–15901CrossRefPubMedGoogle Scholar
  79. 79.
    Kumar N, Lindberg J, David K, Morris J, Menoyo J (2009) Real-world doxercalciferol treatment in SHPT CKD stage 3 and 4: an analysis of change in iPTH and accordance to KDOQI recommendations. Am J Nephrol 29:71–78CrossRefPubMedGoogle Scholar
  80. 80.
    Seeherunvong W, Nwobi O, Abitbol CL, Chandar J, Strauss J, Zilleruelo G (2006) Paricalcitol versus calcitriol treatment for hyperparathyroidism in pediatric hemodialysis patients. Pediatr Nephrol 21:1434–1439CrossRefPubMedGoogle Scholar
  81. 81.
    Greenbaum LA, Benador N, Goldstein SL, Paredes A, Melnick JZ, Mattingly S, Amdahl M, Williams LA, Salusky IB (2007) Intravenous paricalcitol for treatment of secondary hyperparathyroidism in children on hemodialysis. Am J Kidney Dis 49:814–823CrossRefPubMedGoogle Scholar
  82. 82.
    Gomez-Alonso C, Naves-Diaz ML, Fernandez-Martin JL, Diaz-Lopez JB, Fernandez- Coto MT, Cannata-Andia JB (2003) Vitamin D status and secondary hyperparathyroidism: the importance of 25-hydroxyvitamin D cut-off levels. Kidney Int Suppl 63:S44–S48Google Scholar
  83. 83.
    Cozzolino M, Brancaccio D (2008) VDRAs versus calcimimetics: better safe than sorry? Kidney Int 74:966, author reply 966–967CrossRefPubMedGoogle Scholar
  84. 84.
    Gonzalez EA, Sachdeva A, Oliver DA, Martin KJ (2004) Vitamin D insufficiency and deficiency in chronic kidney disease. A single center observational study. Am J Nephrol 24:503–510CrossRefPubMedGoogle Scholar
  85. 85.
    Cannata-Andia JB, Gomez Alonso C (2002) Vitamin D deficiency: a neglected aspect of disturbed calcium metabolism in renal failure. Nephrol Dial Transplant 17:1875–1878CrossRefPubMedGoogle Scholar
  86. 86.
    Greer FR (2008) 25-Hydroxyvitamin D: functional outcomes in infants and young children. Am J Clin Nutr 88:529S–533SPubMedGoogle Scholar
  87. 87.
    Menon S, Valentini RP, Hidalgo G, Peschansky L, Mattoo TK (2008) Vitamin D insufficiency and hyperparathyroidism in children with chronic kidney disease. Pediatr Nephrol 23:1831–1836CrossRefPubMedGoogle Scholar
  88. 88.
    Seeherunvong W, Abitbol CL, Chandar J, Zilleruelo G, Freundlich M (2009) Vitamin D insufficiency and deficiency in children with early chronic kidney disease. J Pediatr 154:906–911CrossRefPubMedGoogle Scholar
  89. 89.
    Moe SM, Drueke TB, Block G, Cannata Andía JB, Elder GJ, Fukagawa M, Jorgetti V, Ketteler M, Lagman CB, Levin A, Macleod M, McCann L, McCulough PA, Ott SM, Wang AY, Weisinger JR, Wheeler DC (2009) KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease related mineral and bone disorders (CKD-MBD). Kidney Int 76(Suppl 113):S1–S130Google Scholar

Copyright information

© IPNA 2010

Authors and Affiliations

  • Jorge B. Cannata-Andía
    • 1
  • Minerva Rodriguez-García
    • 1
  • Pablo Román-García
    • 1
  • Diego Tuñón-le Poultel
    • 1
  • Francisco López-Hernández
    • 2
  • Diego Rodríguez-Puyol
    • 3
  1. 1.Bone and Mineral Research Unit, Instituto Reina Sofia de InvestigaciónREDinREN ISCIII, Hospital Universitario Central de Asturias, Universidad de OviedoAsturiasSpain
  2. 2.Research Unit, Hospital Universitario de SalamancaInstituto Reina Sofía de Investigación, REDinREN ISCIIISalamancaSpain
  3. 3.Nephrology Section and Research Unit, Hospital Príncipe de AsturiasInstituto Reina Sofía de Investigación, REDinREN ISCIIIAlcalá de HanaresSpain

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