Seminars in Nephrology
Volume 29, Issue 2 , Pages 113-121 , March 2009

Role of Vitamin D in Chronic Kidney Disease

  • Tejas V. Patel, MD, MPH

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Tejas V. Patel, MD, MPH, Renal Division, Brigham and Women's Hospital, MRB-4, 75 Francis St, Boston, MA 02115
  • ,
  • Ajay K. Singh, MB

References 

  1. Anavekar NS, McMurray JJ, Velazquez EJ, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004;351:1285–1295
  2. USRDS morbidity and mortality 2007 data. [cited 2008 August 15]. Available from: http://www.usrds.org/2007/pdf/06_hosp_morte_07.pdf.
  3. Zoccali C, Tripepi G, Mallamaci F. Predictors of cardiovascular death in ESRD. Semin Nephrol. 2005;25:358–362
  4. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42:S1–S201
  5. Martin KJ, Gonzalez EA. Vitamin D analogs: actions and role in the treatment of secondary hyperparathyroidism. Semin Nephrol. 2004;24:456–459
  6. Wolf G. The discovery of vitamin D: the contribution of Adolf Windaus. J Nutr. 2004;134:1299–1302
  7. Slatopolsky E, Weerts C, Thielan J, Horst R, Harter H, Martin KJ. Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxy-cholecalciferol in uremic patients. J Clin Invest. 1984;74:2136–2143
  8. Brunette MG, Chan M, Ferriere C, Roberts KD. Site of 1,25(OH)2 vitamin D3 synthesis in the kidney. Nature. 1978;276:287–289
  9. Christakos S, Dhawan P, Liu Y, Peng X, Porta A. New insights into the mechanisms of vitamin D action. J Cell Biochem. 2003;88:695–705
  10. Kuro-o M. Klotho as a regulator of oxidative stress and senescence. Biol Chem. 2008;389:233–241
  11. Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390:45–51
  12. Sitara D, Razzaque MS, Hesse M, et al. Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice. Matrix Biol. 2004;23:421–432
  13. Liu S, Tang W, Zhou J, et al. Fibroblast growth factor 23 is a counter-regulatory phosphaturic hormone for vitamin D. J Am Soc Nephrol. 2006;17:1305–1315
  14. Krajisnik T, Bjorklund P, Marsell R, et al. Fibroblast growth factor-23 regulates parathyroid hormone and 1alpha-hydroxylase expression in cultured bovine parathyroid cells. J Endocrinol. 2007;195:125–131
  15. Liu S, Gupta A, Quarles LD. Emerging role of fibroblast growth factor 23 in a bone-kidney axis regulating systemic phosphate homeostasis and extracellular matrix mineralization. Curr Opin Nephrol Hypertens. 2007;16:329–335
  16. Fliser D, Kollerits B, Neyer U, et al. Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol. 2007;18:2600–2608
  17. Gutierrez OM, Mannstadt M, Isakova T, et al. fibroblast growth factor 23 and mortality among patients undergoing hemodialysis. N Engl J Med. 2008;359:584–592
  18. Memon F, El-Abbadi M, Nakatani T, Taguchi T, Lanske B, Razzaque MS. Does Fgf23-klotho activity influence vascular and soft tissue calcification through regulating mineral ion metabolism?. Kidney Int. 2008;74:566–570
  19. Torres PU, Prie D, Molina-Bletry V, Beck L, Silve C, Friedlander G. Klotho: an antiaging protein involved in mineral and vitamin D metabolism. Kidney Int. 2007;71:730–737
  20. Shoji T, Shinohara K, Kimoto E, et al. Lower risk for cardiovascular mortality in oral 1alpha-hydroxy vitamin D3 users in a haemodialysis population. Nephrol Dial Transplant. 2004;19:179–184
  21. Tentori F, Hunt WC, Stidley CA, et al. Mortality risk among hemodialysis patients receiving different vitamin D analogs. Kidney Int. 2006;70:1858–1865
  22. Melamed ML, Eustace JA, Plantinga L, et al. Changes in serum calcium, phosphate, and PTH and the risk of death in incident dialysis patients: a longitudinal study. Kidney Int. 2006;70:351–357
  23. Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus JM, Thadhani R. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003;349:446–456
  24. Teng M, Wolf M, Ofsthun MN, et al. Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol. 2005;16:1115–1125
  25. Palmer SC, McGregor DO, Macaskill P, Craig JC, Elder GJ, Strippoli GF. Meta-analysis: vitamin D compounds in chronic kidney disease. Ann Intern Med. 2007;147:840–853
  26. Thadhani R. Activated vitamin D sterols in kidney disease. Lancet. 2008;371:542–544
  27. Kovesdy CP, Ahmadzadeh S, Anderson JE, Kalantar-Zadeh K. Association of activated vitamin D treatment and mortality in chronic kidney disease. Arch Intern Med. 2008;168:397–403
  28. Shoben AB, Rudser KD, de Boer IH, Young B, Kestenbaum B. Association of oral calcitriol with improved survival in nondialyzed CKD. J Am Soc Nephrol. 2008;19:1613–1619
  29. 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. 2000;342:1478–1483
  30. Milliner DS, Zinsmeister AR, Lieberman E, Landing B. Soft tissue calcification in pediatric patients with end-stage renal disease. Kidney Int. 1990;38:931–936
  31. Goldsmith DJ, Covic A, Sambrook PA, Ackrill P. Vascular calcification in long-term haemodialysis patients in a single unit: a retrospective analysis. Nephron. 1997;77:37–43
  32. Berlyne GM, Mallick NP. Arterial calcification after vitamin D. Lancet. 1969;1:416
  33. Kingma JG, Roy PE. Ultrastructural study of hypervitaminosis D induced arterial calcification in Wistar rats. Artery. 1988;16:51–61
  34. Watson KE, Abrolat ML, Malone LL, et al. Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation. 1997;96:1755–1760
  35. Andress DL. Vitamin D in chronic kidney disease: a systemic role for selective vitamin D receptor activation. Kidney Int. 2006;69:33–43
  36. Drissi H, Pouliot A, Koolloos C, et al. 1,25-(OH)2-vitamin D3 suppresses the bone-related Runx2/Cbfa1 gene promoter. Exp Cell Res. 2002;274:323–333
  37. Mathew S, Lund RJ, Chaudhary LR, Geurs T, Hruska KA. Vitamin D receptor activators can protect against vascular calcification. J Am Soc Nephrol. 2008;19:1509–1519
  38. Cardus A, Panizo S, Parisi E, Fernandez E, Valdivielso JM. Differential effects of vitamin D analogs on vascular calcification. J Bone Miner Res. 2007;22:860–866
  39. Noonan W, Koch K, Nakane M, et al. Differential effects of vitamin D receptor activators on aortic calcification and pulse wave velocity in uraemic rats. Nephrol Dial Transplant. 2008;23:3824–3830
  40. Fine A, Zacharias J. Calciphylaxis is usually non-ulcerating: risk factors, outcome and therapy. Kidney Int. 2002;61:2210–2217
  41. Nigwekar SU, Wolf M, Sterns RH, Hix JK. Calciphylaxis from nonuremic causes: a systematic review. Clin J Am Soc Nephrol. 2008;3:1139–1143
  42. Foley RN. Clinical epidemiology of cardiac disease in dialysis patients: left ventricular hypertrophy, ischemic heart disease, and cardiac failure. Semin Dial. 2003;16:111–117
  43. Pilz S, Marz W, Wellnitz B, et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab. 2008;93:3927–3935
  44. Xiang W, Kong J, Chen S, et al. Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab. 2005;288:E125–E132
  45. Bodyak N, Ayus JC, Achinger S, et al. Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals. Proc Natl Acad Sci U S A. 2007;104:16810–16815
  46. Thadhani R. Targeted ablation of the vitamin D 1alpha-hydroxylase gene: getting to the heart of the matter. Kidney Int. 2008;74:141–143
  47. Zhou C, Lu F, Cao K, Xu D, Goltzman D, Miao D. Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1alpha-hydroxylase knockout mice. Kidney Int. 2008;74:170–179
  48. Becker L, Koleganova N, Piecha G, Geldyyev A, Noronha IL, Waldherr R, et al. Effect of paricalcitol and calcitriol on cardiovascular disease in uninephrectomized ApoE knockout mice. Paper presented at: American Society of Nephrology Annual Meeting; 2007;Nov 2-5; San Francisco, CA
  49. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am J Clin Nutr. 2006;83:754–759
  50. Park CW, Oh YS, Shin YS, et al. Intravenous calcitriol regresses myocardial hypertrophy in hemodialysis patients with secondary hyperparathyroidism. Am J Kidney Dis. 1999;33:73–81
  51. Brumbaugh PF, Haussler MR. Specific binding of 1alpha,25-dihydroxycholecalciferol to nuclear components of chick intestine. J Biol Chem. 1975;250:1588–1594
  52. Levin A, Gutierrez O, Andress DL, Wolf M. Deficiencies of 25D, 1,25D and inflammation are associated with albuminuria. Paper presented at: American Society of Nephrology Annual Meeting; 2007;Nov 2-5; San Francisco, CA
  53. Agarwal R, Acharya M, Tian J, et al. Antiproteinuric effect of oral paricalcitol in chronic kidney disease. Kidney Int. 2005;68:2823–2828
  54. Alborzi P, Patel NA, Peterson C, et al. Paricalcitol reduces albuminuria and inflammation in chronic kidney disease: a randomized double-blind pilot trial. Hypertension. 2008;52:249–255
  55. Panichi V, Migliori M, Taccola D, et al. Effects of 1,25(OH)2D3 in experimental mesangial proliferative nephritis in rats. Kidney Int. 2001;60:87–95
  56. Kuhlmann A, Haas CS, Gross ML, et al. 1,25-dihydroxyvitamin D3 decreases podocyte loss and podocyte hypertrophy in the subtotally nephrectomized rat. Am J Physiol Renal Physiol. 2004;286:F526–F533
  57. Makibayashi K, Tatematsu M, Hirata M, et al. A vitamin D analog ameliorates glomerular injury on rat glomerulonephritis. Am J Pathol. 2001;158:1733–1741
  58. Tan X, Li Y, Liu Y. Therapeutic role and potential mechanisms of active vitamin D in renal interstitial fibrosis. J Steroid Biochem Mol Biol. 2007;103:491–496
  59. [cited 2008 June 9]. Available from: http://nobelprize.org/nobel_prizes/medicine/laureates/1929/.
  60. Vanholder R, Van Biesen W. Incidence of infectious morbidity and mortality in dialysis patients. Blood Purif. 2002;20:477–480
  61. Bikle DD. Vitamin D and the immune system: role in protection against bacterial infection. Curr Opin Nephrol Hypertens. 2008;17:348–352
  62. Liu PT, Stenger S, Li H, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770–1773
  63. Mandayam S, Shahinian VB. Are chronic dialysis patients at increased risk for cancer?. J Nephrol. 2008;21:166–174
  64. Beer TM, Myrthue A. Calcitriol in cancer treatment: from the lab to the clinic. Mol Cancer Ther. 2004;3:373–381
  65. Guyton KZ, Kensler TW, Posner GH. Vitamin D and vitamin D analogs as cancer chemopreventive agents. Nutr Rev. 2003;61:227–238
  66. Asakura H, Aoshima K, Suga Y, et al. Beneficial effect of the active form of vitamin D3 against LPS-induced DIC but not against tissue-factor-induced DIC in rat models. Thromb Haemost. 2001;85:287–290
  67. Aihara K, Azuma H, Akaike M, et al. Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice. J Biol Chem. 2004;279:35798–35802
  68. Dusso AS, Sato T, Arcidiacono MV, et al. Pathogenic mechanisms for parathyroid hyperplasia. Kidney Int Suppl. 2006;S8-1
  69. Arcidiacono MV, Sato T, Alvarez-Hernandez D, et al. EGFR activation increases parathyroid hyperplasia and calcitriol resistance in kidney disease. J Am Soc Nephrol. 2008;19:310–320
  70. Tokumoto M, Alvarez-Hernandez D, Archidiacono MV, Andia JC, Skatopolsky E, Dusso A. Contribution of reduced parathyroid vitamin D receptor (VDR) to the switch from diffuse to nodular growth in secondary hyperparathyroidism. Paper presented at: American Society of Nephrology Annual Meeting; 2007;Nov 2-5; San Francisco, CA
  71. Blair D, Byham-Gray L, Lewis E, McCaffrey S. Prevalence of vitamin D [25(OH)D] deficiency and effects of supplementation with ergocalciferol (vitamin D2) in stage 5 chronic kidney disease patients. J Ren Nutr. 2008;18:375–382
  72. Mehrotra R, Kermah D, Budoff M, et al. Hypovitaminosis D in chronic kidney disease. Clin J Am Soc Nephrol. 2008;3:1144–1151
  73. Tokmak F, Quack I, Schieren G, et al. High-dose cholecalciferol to correct vitamin D deficiency in haemodialysis patients. Nephrol Dial Transplant. 2008;23:4016–4020
  74. Chandra P, Binongo JN, Ziegler TR, et al. Cholecalciferol (vitamin D3) therapy and vitamin D insufficiency in patients with chronic kidney disease: a randomized controlled pilot study. Endocr Pract. 2008;14:10–17
  75. Chonchol M, Scragg R. 25-Hydroxyvitamin D, insulin resistance, and kidney function in the Third National Health and Nutrition Examination Survey. Kidney Int. 2007;71:134–139
  76. Wang TJ, Pencina MJ, Booth SL, et al. Vitamin D deficiency and risk of cardiovascular disease. Circulation. 2008;117:503–511
  77. Martins D, Wolf M, Pan D, et al. Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med. 2007;167:1159–1165
  78. Hermann M, Ruschitzka F. Vitamin D and hypertension. Curr Hypertens Rep. 2008;10:49–51
  79. de Boer IH, Ioannou GN, Kestenbaum B, Brunzell JD, Weiss NS. 25-hydroxyvitamin D levels and albuminuria in the Third National Health and Nutrition Examination Survey (NHANES III). Am J Kidney Dis. 2007;50:69–77
  80. Kautzky-Willer A, Pacini G, Barnas U, et al. Intravenous calcitriol normalizes insulin sensitivity in uremic patients. Kidney Int. 1995;47:200–206
  81. Perez-Castrillon JL, Vega G, Abad L, et al. Effects of atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Am J Cardiol. 2007;99:903–905
  82. Mizobuchi M, Morrissey J, Finch JL, et al. Combination therapy with an angiotensin-converting enzyme inhibitor and a vitamin D analog suppresses the progression of renal insufficiency in uremic rats. J Am Soc Nephrol. 2007;18:1796–1806
  83. Leon F, Kazim H, Masahide M, Jane F, Slatopolsky E. Combination therapy with paricalcitol and enalapril ameliorated cardiac oxidative injury in uremic rats. Paper presented at: American Society of Nephrology Annual Meeting; 2007;Nov 2-5; San Francisco, CA
  84. Pei YP, Greenwood CM, Chery AL, Wu GG. Racial differences in survival of patients on dialysis. Kidney Int. 2000;58:1293–1299
  85. Gutierrez O, Isakova T, Andress DL, Levin A, Wolf M. Racial differences in the prevalence and severity of disordered mineral metabolism in chronic kidney disease. Paper presented at: American Society of Nephrology Annual Meeting; 2007;Nov 2-5; San Francisco, CA
  86. Wolf M, Betancourt J, Chang Y, et al. Impact of activated vitamin D and race on survival among hemodialysis patients. J Am Soc Nephrol. 2008;19:1379–1388
  87. Wolf M. Active vitamin D and survival. J Am Soc Nephrol. 2008;19:1442–1443

 Dr. Patel was supported by National Institutes of Health grant T32-DK07527-23.

PII: S0270-9295(09)00005-9

doi: 10.1016/j.semnephrol.2009.01.004

Seminars in Nephrology
Volume 29, Issue 2 , Pages 113-121 , March 2009