International Urology and Nephrology

, Volume 40, Issue 2, pp 427–440

Bone and mineral disorders in pre-dialysis CKD

Review

Abstract

Disorders in calcium, phosphorus, and parathyroid hormone (PTH) are common in chronic kidney disease (CKD) and may be associated with poor outcomes including a higher rate of CKD progression and increased death risk. Although these abnormalities have been examined extensively in patients with CKD stage 5 who are receiving chronic maintenance dialysis, they have not been studied to the same extent at earlier stages of CKD, in spite of the much larger numbers of patients in the early CKD population. We summarize the available literature on outcomes associated with bone and mineral disorders in patients with CKD not yet receiving maintenance dialysis. We have reviewed novel data linking fibroblast growth factor 23 (FGF-23) to phosphorus and vitamin D homeostasis. More rapid CKD progression is linked to hyperphosphatemia and its associated hyperparathyroidism and vitamin D deficiency. Hence, hyperphosphatemia may play a central role in the diverse disorders characterizing CKD. We provide a brief overview of the available treatment recommendations for bone and mineral disorders, with an emphasis on areas needing further research.

Keywords

Chronic kidney disease Parathyroid hormone Hyperphosphatemia Mortality FGF-23 1,25-Dihydroxy-cholecalciferol 

Abbreviations

CKD

Chronic kidney disease

PTH

Parathyroid hormone

FGF-23

Fibroblast growth factor 23

MHD

Maintenance hemodialysis

MBD

Mineral and bone disorder

SHPT

Secondary hyperparathyroidism

GFR

Glomerular filtration rate

MDRD

Modification of diet in renal disease

CV

Cardiovascular

AASK

African American study of hypertension and kidney Disease

1,25(OH)2D

1,25-Dihydroxycholecalciferol

ESRD

End stage renal disease

References

  1. 1.
    Levin A, Bakris GL, Molitch M et al (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 71:31–38PubMedGoogle Scholar
  2. 2.
    Block GA, Klassen PS, Lazarus JM et al (2004) Mineral metabolism, mortality, and morbidity in maintenance hemodialysis. J Am Soc Nephrol 15:2208–2218PubMedGoogle Scholar
  3. 3.
    Kalantar-Zadeh K, Kuwae N, Regidor DL et al (2006) Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients. Kidney Int 70:771–780PubMedGoogle Scholar
  4. 4.
    Moe S, Drueke T, Cunningham J et al (2006) Definition, evaluation, and classification of renal osteodystrophy: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 69:1945–1953PubMedGoogle Scholar
  5. 5.
    Yu AS (2004) Renal transport of calcium, magnesium and phosphate. In: Brenner BM (ed) Brenner & Rector’s the kidney, 7th edn. Saunders, PhiladelphiaGoogle Scholar
  6. 6.
    Yangawa N, Nakhoul F, Kurokawa K, Lee DB (1994) Physiology of phosphorus metabolism. In: Narins RG (ed) Maxwell and Kleeman’s clinical disorders of fluid and electrolyte metabolism, 5th edn. McGraw-Hill, pp 307–371Google Scholar
  7. 7.
    Portale AA, Booth BE, Tsai HC, Morris RC Jr (1982) Reduced plasma concentration of 1,25-dihydroxyvitamin D in children with moderate renal insufficiency. Kidney Int 21:627–632PubMedGoogle Scholar
  8. 8.
    Eknoyan G, Levin A, Levin N (2003) Bone metabolism and disease in chronic kidney disease. Am J Kidney Dis 42:1–201Google Scholar
  9. 9.
    Gupta A, Winer K, Econs MJ et al (2004) FGF-23 is elevated by chronic hyperphosphatemia. J Clin Endocrinol Metab 89:4489–4492PubMedGoogle Scholar
  10. 10.
    Bricker NS (1972) On the pathogenesis of the uremic state. An exposition of the “trade-off hypothesis”. N Engl J Med 286:1093–1099PubMedCrossRefGoogle Scholar
  11. 11.
    Fukagawa M, Kazama JJ (2006) FGF23: its role in renal bone disease. Pediatr Nephrol 21:1802–1806PubMedGoogle Scholar
  12. 12.
    Gutierrez O, Isakova T, Rhee E et al (2005) Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 16:2205–2215PubMedGoogle Scholar
  13. 13.
    Mucsi I, Hercz G (1998) Control of serum phosphate in patients with renal failure—new approaches. Nephrol Dial Transplant 13:2457–2460PubMedGoogle Scholar
  14. 14.
    K/DOQI (2002) Clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 39:S1–S266Google Scholar
  15. 15.
    Jono S, McKee MD, Murry CE et al (2000) Phosphate regulation of vascular smooth muscle cell calcification. Circ Res 87:E10–E17PubMedGoogle Scholar
  16. 16.
    Kestenbaum B, Sampson JN, Rudser KD et al (2005) Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol 16:520–528PubMedGoogle Scholar
  17. 17.
    Menon V, Greene T, Pereira AA et al (2005) Relationship of phosphorus and calcium—phosphorus product with mortality in CKD. Am J Kidney Dis 46:455–463PubMedGoogle Scholar
  18. 18.
    Voormolen N, Noordzij M, Grootendorst DC et al (2007) High plasma phosphate as a risk factor for decline in renal function and mortality in pre-dialysis patients. Nephrol Dial Transplant 22:2909–2916PubMedGoogle Scholar
  19. 19.
    Tonelli M, Sacks F, Pfeffer M et al (2005) Relation between serum phosphate level and cardiovascular event rate in people with coronary disease. Circulation 112:2627–2633PubMedGoogle Scholar
  20. 20.
    Chen NX, O’Neill KD, Duan D, Moe SM (2002) Phosphorus and uremic serum up-regulate osteopontin expression in vascular smooth muscle cells. Kidney Int 62:1724–1731PubMedGoogle Scholar
  21. 21.
    Schwarz S, Trivedi BK, Kalantar-Zadeh K, Kovesdy CP (2006) Association of disorders in mineral metabolism with progression of chronic kidney disease. Clin J Am Soc Nephrol 1:825–831PubMedGoogle Scholar
  22. 22.
    Norris KC, Greene T, Kopple J et al (2006) Baseline predictors of renal disease progression in the African American study of hypertension and kidney disease. J Am Soc Nephrol 17:2928–2936PubMedGoogle Scholar
  23. 23.
    Barsotti G, Morelli E, Giannoni A et al (1983) Restricted phosphorus and nitrogen intake to slow the progression of chronic renal failure: a controlled trial. Kidney Int Suppl 16:S278–S284PubMedGoogle Scholar
  24. 24.
    Maschio G, Oldrizzi L, Tessitore N et al (1982) Effects of dietary protein and phosphorus restriction on the progression of early renal failure. Kidney Int 22:371–376PubMedGoogle Scholar
  25. 25.
    Ibels LS, Alfrey AC, Haut L, Huffer WE (1978) Preservation of function in experimental renal disease by dietary restriction of phosphate. N Engl J Med 298:122–126PubMedCrossRefGoogle Scholar
  26. 26.
    Karlinsky ML, Haut L, Buddington B et al (1980) Preservation of renal function in experimental glomerulonephritis. Kidney Int 17:293–302PubMedGoogle Scholar
  27. 27.
    Lumlertgul D, Burke TJ, Gillum DM et al (1986) Phosphate depletion arrests progression of chronic renal failure independent of protein intake. Kidney Int 29:658–666PubMedGoogle Scholar
  28. 28.
    Kraus ES, Cheng L, Sikorski I, Spector DA (1993) Effect of phosphorus restriction on renal response to oral and intravenous protein loads in rats. Am J Physiol 264:F752–F759PubMedGoogle Scholar
  29. 29.
    Ritz E, Gross ML, Dikow R (2005) Role of calcium–phosphorous disorders in the progression of renal failure. Kidney Int Suppl 99:S66–S70PubMedGoogle Scholar
  30. 30.
    Klahr S, Levey AS, Beck GJ et al (1994) The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of diet in renal disease study group. N Engl J Med 330:877–884PubMedGoogle Scholar
  31. 31.
    Sampathkumar K, Selvam M, Sooraj YS et al (2006) Extended release nicotinic acid—a novel oral agent for phosphate control. Int Urol Nephrol 38:171–174PubMedGoogle Scholar
  32. 32.
    Llach F, Massry SG (1985) On the mechanism of secondary hyperparathyroidism in moderate renal insufficiency. J Clin Endocrinol Metab 61:601–606PubMedGoogle Scholar
  33. 33.
    Salusky IB, Foley J, Nelson P, Goodman WG (1991) Aluminum accumulation during treatment with aluminum hydroxide and dialysis in children and young adults with chronic renal disease. N Engl J Med 324:527–531PubMedCrossRefGoogle Scholar
  34. 34.
    Thurston H, Swales JD (1971) Aluminium and chronic renal failure. Br Med J 4:490PubMedCrossRefGoogle Scholar
  35. 35.
    Slatopolsky E, Weerts C, Lopez-Hilker S et al (1986) Calcium carbonate as a phosphate binder in patients with chronic renal failure undergoing dialysis. N Engl J Med 315:157–161PubMedCrossRefGoogle Scholar
  36. 36.
    Braun J, Oldendorf M, Moshage W et al (1996) Electron beam computed tomography in the evaluation of cardiac calcification in chronic dialysis patients. Am J Kidney Dis 27:394–401PubMedGoogle Scholar
  37. 37.
    Goodman WG, Goldin J, Kuizon BD et al (2000) Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. N Engl J Med 342:1478–1483PubMedGoogle Scholar
  38. 38.
    Guerin AP, London GM, Marchais SJ, Metivier F (2000) Arterial stiffening and vascular calcifications in end-stage renal disease. Nephrol Dial Transplant 15:1014–1021PubMedGoogle Scholar
  39. 39.
    London GM, Guerin AP, Marchais SJ et al (2003) Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 18:1731–1740PubMedGoogle Scholar
  40. 40.
    Kovesdy CP, Mehrotra R, Kalantar-Zadeh K (2008) Battleground: chronic kidney disorders mineral and bone disease—calcium obsession, vitamin D, and binder confusion. Clin J Am Soc Nephrol 3:168–173PubMedGoogle Scholar
  41. 41.
    Mehrotra R, Budoff M, Christenson P et al (2004) Determinants of coronary artery calcification in diabetics with and without nephropathy. Kidney Int 66:2022–2031PubMedGoogle Scholar
  42. 42.
    Mehrotra R, Budoff M, Hokanson JE et al (2005) Progression of coronary artery calcification in diabetics with and without chronic kidney disease. Kidney Int 68:1258–1266PubMedGoogle Scholar
  43. 43.
    Qunibi WY, Abouzahr F, Mizani MR et al (2005) Cardiovascular calcification in Hispanic Americans (HA) with chronic kidney disease (CKD) due to type 2 diabetes. Kidney Int 68:271–277PubMedGoogle Scholar
  44. 44.
    Russo D, Palmiero G, De Blasio AP et al (2004) Coronary artery calcification in patients with CRF not undergoing dialysis. Am J Kidney Dis 44:1024–1030PubMedGoogle Scholar
  45. 45.
    Tomiyama C, Higa A, Dalboni MA et al (2006) The impact of traditional and non-traditional risk factors on coronary calcification in pre-dialysis patients. Nephrol Dial Transplant 21:2464–2471PubMedGoogle Scholar
  46. 46.
    Russo D, Miranda I, Ruocco C et al (2007) The progression of coronary artery calcification in predialysis patients on calcium carbonate or sevelamer. Kidney Int 72(10):1255–1261PubMedGoogle Scholar
  47. 47.
    Shantouf R, Budoff MJ, Ahmadi N et al (2007) Effects of sevelamer and calcium-based phosphate binders on lipid and inflammatory markers in hemodialysis patients. Am J Nephrol 28:275–279PubMedGoogle Scholar
  48. 48.
    De Boer IH, Gorodetskaya I, Young B et al (2002) The severity of secondary hyperparathyroidism in chronic renal insufficiency is GFR-dependent, race-dependent, and associated with cardiovascular disease. J Am Soc Nephrol 13:2762–2769PubMedGoogle Scholar
  49. 49.
    Fajtova VT, Sayegh MH, Hickey N et al (1995) Intact parathyroid hormone levels in renal insufficiency. Calcif Tissue Int 57:329–335PubMedGoogle Scholar
  50. 50.
    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 29:496–502PubMedGoogle Scholar
  51. 51.
    Pitts TO, Piraino BH, Mitro R et al (1988) Hyperparathyroidism and 1,25-dihydroxyvitamin D deficiency in mild, moderate, and severe renal failure. J Clin Endocrinol Metab 67:876–881PubMedCrossRefGoogle Scholar
  52. 52.
    Reiss E, Canterbury JM, Kanter A (1969) Circulating parathyroid hormone concentration in chronic renal insufficiency. Arch Intern Med 124:417–422PubMedGoogle Scholar
  53. 53.
    St John A, Thomas MB, Davies CP et al (1992) Determinants of intact parathyroid hormone and free 1,25-dihydroxyvitamin D levels in mild and moderate renal failure. Nephron 61:422–427Google Scholar
  54. 54.
    Korkor AB (1987) Reduced binding of [3H]1,25-dihydroxyvitamin D3 in the parathyroid glands of patients with renal failure. N Engl J Med 316:1573–1577PubMedCrossRefGoogle Scholar
  55. 55.
    Gogusev J, Duchambon P, Hory B et al (1997) Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism. Kidney Int 51:328–336PubMedGoogle Scholar
  56. 56.
    Kates DM, Sherrard DJ, Andress DL (1997) Evidence that serum phosphate is independently associated with serum PTH in patients with chronic renal failure. Am J Kidney Dis 30:809–813PubMedGoogle Scholar
  57. 57.
    Yamamoto M, Igarashi T, Muramatsu M et al (1989) Hypocalcemia increases and hypercalcemia decreases the steady-state level of parathyroid hormone messenger RNA in the rat. J Clin Invest 83:1053–1056PubMedGoogle Scholar
  58. 58.
    Llach F, Massry SG, Singer FR et al (1975) Skeletal resistance to endogenous parathyroid hormone in patients with early renal failure. A possible cause for secondary hyperparathyroidism. J Clin Endocrinol Metab 41:339–345PubMedGoogle Scholar
  59. 59.
    Fuleihan GE, Gundberg CM, Gleason R et al (1994) Racial differences in parathyroid hormone dynamics. J Clin Endocrinol Metab 79:1642–1647PubMedGoogle Scholar
  60. 60.
    Gupta A, Kallenbach LR, Zasuwa G, Divine GW (2000) Race is a major determinant of secondary hyperparathyroidism in uremic patients. J Am Soc Nephrol 11:330–334PubMedGoogle Scholar
  61. 61.
    Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K (2007) Obesity is associated with secondary hyperparathyroidism in men with moderate and severe chronic kidney disease. Clin J Am Soc Nephrol 2:1024–1029PubMedGoogle Scholar
  62. 62.
    Vincenti F, Arnaud SB, Recker R et al (1984) Parathyroid and bone response of the diabetic patient to uremia. Kidney Int 25:677–682PubMedGoogle Scholar
  63. 63.
    Hutchison AJ, Whitehouse RW, Boulton HF et al (1993) Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology in end-stage renal disease. Kidney Int 44:1071–1077PubMedGoogle Scholar
  64. 64.
    Malluche HH, Ritz E, Lange HP et al (1976) Bone histology in incipient and advanced renal failure. Kidney Int 9:355–362PubMedGoogle Scholar
  65. 65.
    Rix M, Andreassen H, Eskildsen P et al (1999) Bone mineral density and biochemical markers of bone turnover in patients with predialysis chronic renal failure. Kidney Int 56:1084–1093PubMedGoogle Scholar
  66. 66.
    Sherrard DJ, Hercz G, Pei Y et al (1993) The spectrum of bone disease in end-stage renal failure—an evolving disorder. Kidney Int 43:436–442PubMedGoogle Scholar
  67. 67.
    Massry SG, Popovtzer MM, Coburn JW et al (1968) Intractable pruritus as a manifestation of secondary hyperparathyroidism in uremia. Disappearance of itching after subtotal parathyroidectomy. N Engl J Med 279:697–700PubMedCrossRefGoogle Scholar
  68. 68.
    Rao DS, Shih MS, Mohini R (1993) Effect of serum parathyroid hormone and bone marrow fibrosis on the response to erythropoietin in uremia. N Engl J Med 328:171–175PubMedGoogle Scholar
  69. 69.
    Bogicevic M, Stefanovic V (1988) Relationship between parathyroid hormone and pituitary-testicular axis in patients on maintenance hemodialysis. Exp Clin Endocrinol 92:357–362PubMedGoogle Scholar
  70. 70.
    Tonner DR, Schlechte JA (1993) Neurologic complications of thyroid and parathyroid disease. Med Clin North Am 77:251–263PubMedGoogle Scholar
  71. 71.
    Fellner SK, Lang RM, Neumann A et al (1991) Parathyroid hormone and myocardial performance in dialysis patients. Am J Kidney Dis 18:320–325PubMedGoogle Scholar
  72. 72.
    London GM (2002) Left ventricular alterations and end-stage renal disease. Nephrol Dial Transplant 1 [17 Suppl]:29–36Google Scholar
  73. 73.
    Tseke P, Grapsa E, Stamatelopoulos K et al (2006) Atherosclerotic risk factors and carotid stiffness in elderly asymptomatic HD patients. Int Urol Nephrol 38:801–809PubMedGoogle Scholar
  74. 74.
    Kovesdy CP, Ahmadzadeh A, Anderson JE, Kalantar-Zadeh K (2008) Outcomes associated with secondary hyperparathyroidism in men with moderate to severe chronic kidney disease. Kidney Int (in press)Google Scholar
  75. 75.
    Avram MM, Mittman N, Myint MM, Fein P (2001) Importance of low serum intact parathyroid hormone as a predictor of mortality in hemodialysis and peritoneal dialysis patients: 14 years of prospective observation. Am J Kidney Dis 38:1351–1357PubMedGoogle Scholar
  76. 76.
    Fouque D, Guebre-Egziabher F (2007) An update on nutrition in chronic kidney disease. Int Urol Nephrol 39:239–246PubMedGoogle Scholar
  77. 77.
    Mafra D, Farage NE, Azevedo DL et al (2007) Impact of serum albumin and body-mass index on survival in hemodialysis patients. Int Urol Nephrol 39:619–624PubMedGoogle Scholar
  78. 78.
    Massry SG, Smogorzewski M (1994) Mechanisms through which parathyroid hormone mediates its deleterious effects on organ function in uremia. Semin Nephrol 14:219–231PubMedGoogle Scholar
  79. 79.
    Mazzaferro S, Coen G, Bandini S et al (1993) Role of ageing, chronic renal failure and dialysis in the calcification of mitral annulus. Nephrol Dial Transplant 8:335–340PubMedGoogle Scholar
  80. 80.
    Chiu KC, Chuang LM, Lee NP et al (2000) Insulin sensitivity is inversely correlated with plasma intact parathyroid hormone level. Metabolism 49:1501–1505PubMedGoogle Scholar
  81. 81.
    Wareham NJ, Byrne CD, Carr C et al (1997) Glucose intolerance is associated with altered calcium homeostasis: a possible link between increased serum calcium concentration and cardiovascular disease mortality. Metabolism 46:1171–1177PubMedGoogle Scholar
  82. 82.
    Gadallah MF, el-Shahawy M, Andrews G et al (2001) Factors modulating cytosolic calcium. Role in lipid metabolism and cardiovascular morbidity and mortality in peritoneal dialysis patients. Adv Perit Dial 17:29–36PubMedGoogle Scholar
  83. 83.
    Meytes D, Bogin E, Ma A et al (1981) Effect of parathyroid hormone on erythropoiesis. J Clin Invest 67:1263–1269PubMedGoogle Scholar
  84. 84.
    Neves PL, Trivino J, Casaubon F et al (2002) Elderly patients on chronic hemodialysis: effect of the secondary hyperparathyroidism on the hemoglobin level. Int Urol Nephrol 34:147–149PubMedGoogle Scholar
  85. 85.
    Neves PL, Trivino J, Casaubon F et al (2006) Elderly patients on chronic hemodialysis with hyperparathyroidism: increase of hemoglobin level after intravenous calcitriol. Int Urol Nephrol 38:175–177PubMedGoogle Scholar
  86. 86.
    Massry SG, Alexiewicz JM, Gaciong Z, Klinger M (1991) Secondary hyperparathyroidism and the immune system in chronic renal failure. Semin Nephrol 11:186–201PubMedGoogle Scholar
  87. 87.
    Baczynski R, Massry SG, Kohan R et al (1985) Effect of parathyroid hormone on myocardial energy metabolism in the rat. Kidney Int 27:718–725PubMedGoogle Scholar
  88. 88.
    Amann K, Ritz E (1997) Cardiac disease in chronic uremia: pathophysiology. Adv Ren Replace Ther 4:212–224PubMedGoogle Scholar
  89. 89.
    Kosch M, Hausberg M, Vormbrock K et al (2000) Impaired flow-mediated vasodilation of the brachial artery in patients with primary hyperparathyroidism improves after parathyroidectomy. Cardiovasc Res 47:813–818PubMedGoogle Scholar
  90. 90.
    Amann K, Tornig J, Flechtenmacher C et al (1995) Blood-pressure-independent wall thickening of intramyocardial arterioles in experimental uraemia: evidence for a permissive action of PTH. Nephrol Dial Transplant 10:2043–2048PubMedGoogle Scholar
  91. 91.
    Kamycheva E, Sundsfjord J, Jorde R (2004) Serum parathyroid hormone levels predict coronary heart disease: the Tromsø study. Eur J Cardiovasc Prev Rehabil 11:69–74PubMedGoogle Scholar
  92. 92.
    Ichikawa I, Humes HD, Dousa TP, Brenner BM (1978) Influence of parathyroid hormone on glomerular ultrafiltration in the rat. Am J Physiol 234:F393–F401PubMedGoogle Scholar
  93. 93.
    Marchand GR (1985) Effect of parathyroid hormone on the determinants of glomerular filtration in dogs. Am J Physiol 248:F482–F486PubMedGoogle Scholar
  94. 94.
    Lee K, Brown D, Urena P et al (1996) Localization of parathyroid hormone/parathyroid hormone-related peptide receptor mRNA in kidney. Am J Physiol 270:F186–F191PubMedGoogle Scholar
  95. 95.
    Endlich N, Nobiling R, Kriz W, Endlich K (2001) Expression and signaling of parathyroid hormone-related protein in cultured podocytes. Exp Nephrol 9:436–443PubMedGoogle Scholar
  96. 96.
    Shigematsu T, Caverzasio J, Bonjour JP (1993) Parathyroid removal prevents the progression of chronic renal failure induced by high protein diet. Kidney Int 44:173–181PubMedGoogle Scholar
  97. 97.
    Baker LR, Abrams L, Roe CJ et al (1989) 1,25(OH)2D3 administration in moderate renal failure: a prospective double-blind trial. Kidney Int 35:661–669PubMedGoogle Scholar
  98. 98.
    Bianchi ML, Colantonio G, Campanini F et al (1994) Calcitriol and calcium carbonate therapy in early chronic renal failure. Nephrol Dial Transplant 9:1595–1599PubMedGoogle Scholar
  99. 99.
    Goodman WG, Coburn JW (1992) The use of 1,25-dihydroxyvitamin D3 in early renal failure. Annu Rev Med 43:227–237PubMedGoogle Scholar
  100. 100.
    Martin KJ, Gonzalez EA, Gellens M 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 9:1427–1432PubMedGoogle Scholar
  101. 101.
    Kazama JJ, Maruyama H, Narita I, Gejyo F (2005) Maxacalcitol is a possible less phosphatemic vitamin D analog. Ther Apher Dial 9:352–354PubMedGoogle Scholar
  102. 102.
    Goodman WG, Hladik GA, Turner SA et al (2002) The calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. J Am Soc Nephrol 13:1017–1024PubMedGoogle Scholar
  103. 103.
    Taskapan H, Wei M, Oreopoulos DG (2006) 25(OH) vitamin D3 in patients with chronic kidney disease and those on dialysis: rediscovering its importance. Int Urol Nephrol 38:323–329PubMedGoogle Scholar
  104. 104.
    Saab G, Young DO, Gincherman Y et al (2007) Prevalence of vitamin D deficiency and the safety and effectiveness of monthly ergocalciferol in hemodialysis patients. Nephron Clin Pract 105:c132–c138PubMedGoogle Scholar
  105. 105.
    Ritter CS, Armbrecht HJ, Slatopolsky E, Brown AJ (2006) 25-Hydroxyvitamin D(3) suppresses PTH synthesis and secretion by bovine parathyroid cells. Kidney Int 70:654–659PubMedGoogle Scholar
  106. 106.
    Teng M, Wolf M, Ofsthun MN et al (2005) Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol 16:1115–1125PubMedGoogle Scholar
  107. 107.
    Tentori F, Hunt WC, Stidley CA et al (2006) Mortality risk among hemodialysis patients receiving different vitamin D analogs. Kidney Int 70:1858–1865PubMedGoogle Scholar
  108. 108.
    Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K (2008) Association of treatment with activated vitamin D and mortality in chronic kidney disease. Arch Intern Med 168:397–403 PubMedGoogle Scholar
  109. 109.
    Shoben AB, Rudser KD, de Boer IH et al (2007) Oral calcitriol use and mortality in non-dialyzed patients with chronic kidney disease [abstract]. J Am Soc Nephrol 18:98AGoogle Scholar
  110. 110.
    Bellows CG, Reimers SM, Heersche JN (1999) Expression of mRNAs for type-I collagen, bone sialoprotein, osteocalcin, and osteopontin at different stages of osteoblastic differentiation and their regulation by 1,25 dihydroxyvitamin D3. Cell Tissue Res 297:249–259PubMedGoogle Scholar
  111. 111.
    Drissi H, Pouliot A, Koolloos C et al (2002) 1,25-(OH)2-vitamin D3 suppresses the bone-related Runx2/Cbfa1 gene promoter. Exp Cell Res 274:323–333PubMedGoogle Scholar
  112. 112.
    Virdi AS, Cook LJ, Oreffo RO, Triffitt JT (1998) Modulation of bone morphogenetic protein-2 and bone morphogenetic protein-4 gene expression in osteoblastic cell lines. Cell Mol Biol (Noisy-le-grand) 44:1237–1246Google Scholar
  113. 113.
    Fraser JD, Otawara Y, Price PA (1988) 1,25-Dihydroxyvitamin D3 stimulates the synthesis of matrix gamma-carboxyglutamic acid protein by osteosarcoma cells. Mutually exclusive expression of vitamin K-dependent bone proteins by clonal osteoblastic cell lines. J Biol Chem 263:911–916PubMedGoogle Scholar
  114. 114.
    Panichi V, De Pietro S, Andreini B et al (1998) Calcitriol modulates in vivo and in vitro cytokine production: a role for intracellular calcium. Kidney Int 54:1463–1469PubMedGoogle Scholar
  115. 115.
    Staeva-Vieira TP, Freedman LP (2002) 1,25-dihydroxyvitamin D3 inhibits IFN-gamma and IL-4 levels during in vitro polarization of primary murine CD4 + T cells. J Immunol 168:1181–1189PubMedGoogle Scholar
  116. 116.
    Barrat FJ, Cua DJ, Boonstra A et al (2002) In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J Exp Med 195:603–616PubMedGoogle Scholar
  117. 117.
    Boonstra A, Barrat FJ, Crain C et al (2001) 1alpha,25-Dihydroxyvitamin d3 has a direct effect on naive CD4(+) T cells to enhance the development of Th2 cells. J Immunol 167:4974–4980PubMedGoogle Scholar
  118. 118.
    Aihara K, Azuma H, Akaike M et al (2004) Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice. J Biol Chem 279:35798–35802PubMedGoogle Scholar
  119. 119.
    Wolf M, Shah A, Gutierrez O et al (2007) Vitamin D levels and early mortality among incident hemodialysis patients. Kidney Int 72:1004–1013PubMedGoogle Scholar
  120. 120.
    Watson KE, Abrolat ML, Malone LL et al (1997) Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation 96:1755–1760PubMedGoogle Scholar
  121. 121.
    Bertoli M, Luisetto G, Ruffatti A et al (1990) Renal function during calcitriol therapy in chronic renal failure. Clin Nephrol 33:98–102PubMedGoogle Scholar
  122. 122.
    Coen G, Mazzaferro S, Manni M et al (1994) No acceleration and possibly slower progression of renal failure during calcitriol treatment in predialysis chronic renal failure. Nephrol Dial Transplant 9:1520PubMedGoogle Scholar
  123. 123.
    Agarwal R, Acharya M, Tian J et al (2005) Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int 68:2823–2828PubMedGoogle Scholar
  124. 124.
    Nagakura K, Abe E, Suda T et al (1986) Inhibitory effect of 1 alpha,25-dihydroxyvitamin D3 on the growth of the renal carcinoma cell line. Kidney Int 29:834–840PubMedGoogle Scholar
  125. 125.
    Penna G, Adorini L (2000) 1 Alpha,25-dihydroxyvitamin D3 inhibits differentiation, maturation, activation, and survival of dendritic cells leading to impaired alloreactive T cell activation. J Immunol 164:2405–2411PubMedGoogle Scholar
  126. 126.
    Gysemans C, Van EE, Overbergh L et al (2002) Treatment of autoimmune diabetes recurrence in non-obese diabetic mice by mouse interferon-beta in combination with an analogue of 1alpha,25-dihydroxyvitamin-D3. Clin Exp Immunol 128:213–220PubMedGoogle Scholar
  127. 127.
    Li YC, Kong J, Wei M et al (2002) 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 110:229–238PubMedGoogle Scholar
  128. 128.
    Charytan C, Coburn JW, Chonchol M et al (2005) Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis. Am J Kidney Dis 46:58–67PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Division of NephrologySalem VA Medical CenterSalemUSA
  2. 2.University of VirginiaCharlottesvilleUSA
  3. 3.Harold Simmons Center for Kidney Disease Research and EpidemiologyTorranceUSA
  4. 4.Division of Nephrology and HypertensionLos Angeles Biomedical Research Institute at Harbor-UCLA Medical CenterTorranceUSA
  5. 5.David Geffen School of Medicine at UCLATorranceUSA

Personalised recommendations