Skip to main content

Advertisement

SpringerLink
Log in

Is 24,25(OH)D level really high in dialysis patients with high FGF23 levels?

  • Nephrology – Review
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Deficiency of 1,25-dihydroxyvitamin D [1,25(OH)2D] and excessive fibroblast growth factor (FGF23) are suggested to be associated with increased mortality in patients with chronic kidney disease (CKD). Generally, 24-hydroxylation has been considered the first step in the degradation pathway of 1,25(OH)2D and 25(OH)D. 24,25-dihydroxyvitamin D [24,25(OH)2D] was believed to be a degradation product, with no important biological effects. However, some data have accumulated showing that 24,25(OH)2D has biological effects on its own. Under conditions of eucalcemia, the synthesis of 24,25(OH)2D is increased, and the synthesis of 1,25(OH)2D is decreased. In patients with CKD, both high parathyroid hormone levels, which decrease the activity of enzyme CYP24A1 (24-hydroxylase), and high FGF23 levels, which increase the activity of enzyme CYP24A1, were often detected. However, information about 24,25(OH)2D levels in these patients is very limited. Whether compensatory changes in levels of FGF23 and 24,25(OH)2D in CKD patients are protective or harmful remain unknown issues. Therefore, more studies are needed to identify the nature of the interactions between these molecules and to fully elucidate their clinical significance.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Shimada T, Kakitani M, Yamazaki Y et al (2004) Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism. J Clin Invest 113:561–568

    PubMed  CAS  Google Scholar 

  2. Sitara D, Razzaque MS, Hesse M et al (2004) Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex-deficient mice. Matrix Biol 23:421–432

    Article  PubMed  CAS  Google Scholar 

  3. Gutiérrez OM (2010) Fibroblast growth factor 23 and disordered vitamin D metabolism in chronic kidney disease: updating the “trade-off” hypothesis. Clin J Am Soc Nephrol 5(9):1710–1716 (Epub 2010 May 27)

    Google Scholar 

  4. Memon F, El-Abbadi M, Nakatani T, Taguchi T, Lanske B, Razzaque MS (2008) Does Fgf23-klotho activity influence vascular and soft tissue calcification through regulating mineral ion metabolism? Kidney Int 74:566–570

    Article  PubMed  CAS  Google Scholar 

  5. Razzaque MS, Lanske B (2006) Hypervitaminosis D and premature aging: lessons learned from Fgf23 and Klotho mutant mice. Trends Mol Med 12:298–305

    Article  PubMed  CAS  Google Scholar 

  6. Hesse M, Frohlich LF, Zeitz U, Lanske B, Erben RG (2007) Ablation of vitamin D signaling rescues bone, mineral, and glucose homeostasis in Fgf-23 deficient mice. Matrix Biol 26:75–84

    Article  PubMed  CAS  Google Scholar 

  7. Razzaque MS, Sitara D, Taguchi T, St-Arnaud R, Lanske B (2006) Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process. FASEB J 20:720–722

    PubMed  CAS  Google Scholar 

  8. Vieth R (1994) Simple method for determining specific binding capacity of vitamin D binding protein and its use to calculate the concentration of ‘free’ 1,25 dihydroxyvitamin D. Clin Chem 40:435–441

    PubMed  CAS  Google Scholar 

  9. Parfitt AM, Mathews CHE, Brommage R, Jarnagin K, DeLuca HF (1984) Calcitriol but no other metabolite of vitamin D is essential for growth and development in the rat. J Clin Invest 73:576–586

    Article  PubMed  CAS  Google Scholar 

  10. Henry HL, Norman AW (1978) Vitamin D: two dihydroxylated metabolites are required for normal chicken egg hatchability. Science 201:835–837

    Article  PubMed  CAS  Google Scholar 

  11. Norman AW, Leathers V, Bishop JE (1983) Normal egg hatchability requires the simultaneous administration to the hen of 1a,25-dihydroxycholecalciferol and 24R,25-dihydroxycholecalciferol. J Nutr 113:2505–2515

    PubMed  CAS  Google Scholar 

  12. Nemere I (1996) Apparent nonnuclear regulation of intestinal phosphate transport: effects of 1,25 dihydroxyvitamin D3,24,25-dihydroxyvitamin D3, and 25-hydroxyvitamin D3. Endocrinology 137:2254–2261

    Article  PubMed  CAS  Google Scholar 

  13. Nemere I (1999) 24,25-Dihydroxyvitamin D3 suppresses the rapid actions of 1,25-dihydroxyvitamin D3 and parathyroid hormone on calcium transport in chick intestine. J Bone Miner Res 14:1543–1549

    Article  PubMed  CAS  Google Scholar 

  14. Zhao B, Nemere I (2002) 1,25(OH)2D3-mediated phosphate uptake in isolated chick intestinal cells: effect of 24,25(OH)2D3, signal transduction activators, and age. J Cell Biochem 86:497–508

    Article  PubMed  CAS  Google Scholar 

  15. Nemere I, Wilson C, Jensen W, Steinbeck M, Rohe B, Farach-Carson MC (2006) Mechanism of 24,25-dihydroxyvitamin D3-mediated inhibition of rapid, 1,25-dihydroxyvitamin D3-induced responses: role of reactive oxygen species. J Cell Biochem 99:1572–1581

    Article  PubMed  CAS  Google Scholar 

  16. Larsson D, Bjornsson BT, Sundell K (1995) Physiological concentrations of 24,25-dihydroxyvitamin D3 rapidly decrease the in vitro intestinal calcium uptake in the Atlantic cod, Gadus morhua. Gen Comp Endocrinol 100:211–217

    Article  PubMed  CAS  Google Scholar 

  17. Khanal RC, Smith NM, Nemere I (2007) Phosphate uptake in chick kidney cells: effects of 1,25(OH)2D3 and 24,25(OH)2D3. Steroids 72(2):158–164

    Article  PubMed  CAS  Google Scholar 

  18. Schwartz Z, Dean DD, Walton JK, Brooks BP, Boyan BD (1995) Treatment of resting zone chondrocytes with 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] induces differentiation into a 1,25-(OH)2D3-responsive phenotype character-istic of growth zone chondrocytes. Endocrinology 136:402–411

    Article  PubMed  CAS  Google Scholar 

  19. Boyan BD, Hurst-Kennedy J, Denison TA, Schwartz Z (2010) 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] controls growth plate development by inhibiting apoptosis in the reserve zone and stimulating response to 1alpha,25(OH)2D3 in hypertrophic cells. J Steroid Biochem Mol Biol 121(1–2):212–216

    Article  PubMed  CAS  Google Scholar 

  20. Ono T, Tanaka H, Yamate T, Nagai Y, Nakamura T, Seino Y (1996) 24R,25-dihydroxyvitamin D3 promotes bone formation without causing excessive resorption in hypophosphatemic mice. Endocrinology 137:2633–2637

    Article  PubMed  CAS  Google Scholar 

  21. Seo E-G, Einhorn TA, Norman AW (1997) 24R,25-dihydroxyvitamin D3: an essential vitamin D3 metabolite for both normal bone integrity and healing of tibial fracture in chicks. Endocrinology 138:3864–3872

    Article  PubMed  CAS  Google Scholar 

  22. Bishop JE, Norman AW, Coburn JW, Roberts PA, Henry HL (1980) Studies on the metabolism of calciferol. Determination of the concentration of 25- hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D in a single two milliliter plasma sample. J Miner Electrolyte Metab 3:181–189

    CAS  Google Scholar 

  23. Wehmeier KR, Alamir AR, Sultan S, Haas MJ, Wong NC, Mooradian AD (2011) 24, 25-dihydroxycholecalciferol but not 25-hydroxycholecalciferol suppresses apolipoprotein A-I gene expression. Life Sci 88(1–2):110–116

    Article  PubMed  CAS  Google Scholar 

  24. Garabedian M, Holick MF, Deluca HF, Boyle IT (1972) Control of 25 hydroxycholecalciferol metabolism by parathyroid glands. Proc Natl Acad Sci USA 69:1673–1676

    Article  PubMed  CAS  Google Scholar 

  25. Zierold C, Mings JA, DeLuca HF (2001) Parathyroid hormone regulates 25-hydroxyvitamin D3–24-hydroxylase mRNA by altering its stability. Proc Natl Acad Sci USA 98(24):13572–13576

    Article  PubMed  CAS  Google Scholar 

  26. Inoue Y, Segawa H, Kaneko I, Yamanaka S, Kusano K, Kawakami E, Furutani J, Ito M, Kuwahata M, Saito H, Fukushima N, Kato S, Kanayama HO, Miyamoto K (2005) Role of the vitamin D receptor in FGF23 action on phosphate metabolism. Biochem J 390:325–331

    Article  PubMed  CAS  Google Scholar 

  27. Wu S, Grieff M, Brown AJ (1997) Regulation of renal vitamin D-24-hydroxylase by phosphate: effects of hypophysectomy, growth hormone and insulin-like growth factor I. Biochem Biophys Res Commun 233:813–817

    Article  PubMed  CAS  Google Scholar 

  28. Kanis JA, Cundy T, Bartlett M, Smith R, Heynen G, Warner GT, Russell RG (1978) Is 24,25-dihydroxycholecalciferol a calcium-regulating hormone in man? Br Med J 1(6124):1382–1386

    Article  PubMed  CAS  Google Scholar 

  29. Mason RS, Lissner D, Wilkinson M, Posen S (1980) Vitamin D metabolites and their relationship to azotaemic osteodystrophy. Clin Endocrinol (Oxf) 13(4):375–385

    Article  CAS  Google Scholar 

  30. Dunstan CR, Hills E, Norman AW, Bishop JE, Mayer E, Wong SY, Eade Y, Johnson JR, George CR, Collett P et al (1985) Treatment of hemodialysis bone disease with 24,25-(OH)2D3 and 1,25-(OH)2D3 alone or in combination. Miner Electrolyte Metab 11(6):358–368

    PubMed  CAS  Google Scholar 

  31. van Diemen-Steenvoorde R, Donckerwolcke RA, Bosch R, Visser WJ, Raymakers JA, Duursma SA (1985) Treatment of renal osteodystrophy in children with dihydrotachysterol and 24,25-dihydroxyvitamin D3. Clin Nephrol 24(6):292–299

    PubMed  Google Scholar 

  32. Piraino BM, Rault R, Greenberg A, Dominguez JH, Wallia R, Houck P, Segre GV, Chen T, Foti FM, Puschett JB (1986) Spontaneous hypercalcemia in patients undergoing dialysis. Etiologic and therapeutic considerations. Am J Med 80(4):607–615

    Article  PubMed  CAS  Google Scholar 

  33. Ben-Ezer D, Shany S, Conforty A, Rapoport J, Edelstein S, Bdolah-Abram T, Kafka DR, Chaimovitz C (1991) Oral administration of 24,25(OH)2D3 suppresses the serum parathyroid hormone levels of dialysis patients. Nephron 58(3):283–287

    Article  PubMed  CAS  Google Scholar 

  34. Varghese Z, Moorhead JF, Farrington K (1992) Effect of 24,25-dihydroxycholecalciferol on intestinal absorption of calcium and phosphate and on parathyroid hormone secretion in chronic renal failure. Nephron 60(3):286–291

    Article  PubMed  CAS  Google Scholar 

  35. Kazama JJ, Wa MF, Yi H, Kumagai M, Yamato H, Taniguchi N, Gejyo F, Arakawa M, Ozawa H, Kurokawa K (1996) 24R, 25-Dihydroxyvitamin D3 ameliorates the high-turnover bone diseases without suppressing parathyroid function in chronic renal failure in rats. Nephrology 2:361–366

    Article  CAS  Google Scholar 

  36. Birkenhäger-Frenkel DH, Pols HA, Zeelenberg J, Eijgelsheim JJ, Schot R, Nigg AL, Weimar W, Mulder PG, Birkenhäger JC (1995) Effects of 24R,25-dihydroxyvitamin D3 in combination with 1 alpha-hydroxyvitamin D3 in predialysis renal insufficiency: biochemistry and histomorphometry of cancellous bone. J Bone Miner Res10(2):197–204

    Google Scholar 

  37. Mortensen BM, Aarseth HP, Ganss R, Haug E, Gautvik KM, Gordeladze JO (1993) 24,25-dihydroxy vitamin D3 treatment inhibits parathyroid-stimulated adenylate cyclase in iliac crest biopsies from uremic patients. Bone 14(2):125–131

    Article  PubMed  CAS  Google Scholar 

  38. Ishimura E, Nishizawa Y, Inaba M, Matsumoto N, Emoto M, Kawagishi T, Shoji S, Okuno S, Kim M, Miki T, Morii H (1999) Serum levels of 1,25-dihydroxyvitamin D, 24,25-dihydroxyvitamin D, and 25-hydroxyvitamin D in nondialyzed patients with chronic renal failure. Kidney Int 55(3):1019–1027

    Article  PubMed  CAS  Google Scholar 

  39. Gal-Moscovici A, Rubinger D, Popovtzer MM (2000) 24,25-dihydroxyvitamin D3 in combination with 1,25-dihydroxyvitamin D3 ameliorates renal osteodystrophy in rats with chronic renal failure. Clin Nephrol 53(5):362–371

    PubMed  CAS  Google Scholar 

  40. Helvig CF, Cuerrier D, Hosfield CM, Ireland B, Kharebov AZ, Kim JW, Ramjit NJ, Ryder K, Tabash SP, Herzenberg AM, Epps TM, Petkovich M (2010) Dysregulation of renal vitamin D metabolism in the uremic rat. Kidney Int 78:463–472

    Article  PubMed  CAS  Google Scholar 

  41. Clements MR, Davies M, Fraser DR, Lumb GA, Mawer EB, Adams PH (1987) Metabolic inactivation of vitamin D is enhanced in primary hyperparathyroidism. Clin Sci 73(6):659–664

    PubMed  CAS  Google Scholar 

  42. Clements MR, Davies M, Hayes ME, Hickey CD, Lumb GA, Mawer EB, Adams PH (1992) The role of 1, 25-dihydroxyvitamin D in the mechanism of acquired vitamin D deficiency. Clin Endocrinol 37(1):17–27

    Article  CAS  Google Scholar 

  43. Nikkilä MT, Saaristo JJ (1989) Serum vitamin D metabolite concentrations in primary hyperparathyroidism. Ann Med 21(4):281–283

    Article  PubMed  Google Scholar 

  44. Christiansen C, Christensen MS, McNair P, Nielsen B, Madsbad S (1982) Vitamin D metabolites in diabetic patients: decreased serum concentration of 24,25-dihydroxyvitamin D. Scand J Clin Lab Invest 42(6):487–491

    Article  PubMed  CAS  Google Scholar 

  45. Taskapan H, Ersoy FF, Passadakis P et al (2006) Severe vitamin D deficiency in chronic renal failure patients on peritoneal dialysis. Clin Nephrol Clin Nephrol 66(4):247–255

    CAS  Google Scholar 

  46. Taskapan H, Wei M, Oreopoulos DG (2006) 25(OH) Vitamin D(3) in patients with chronic kidney disease and those on dialysis: rediscovering its importance. Int Urol Nephrol 38(2):323–329

    Article  PubMed  CAS  Google Scholar 

  47. Bindal ME, Taskapan H (2011) Hypovitaminosis D and insulin resistance in peritoneal dialysis patients. Int Urol Nephrol 43(2):527–534

    Article  PubMed  CAS  Google Scholar 

  48. Taskapan H, Ersoy FF, Passadakis P et al (2005) Body pain during daily activities in patients on peritoneal dialysis. Dial Transplant 2:58–72

    Google Scholar 

  49. Taskapan H, Baysal O, Karahan D, Durmus B, Altay Z, Ulutas O (2011) Vitamin D and muscle strength, functional ability and balance in peritoneal dialysis patients with vitamin D deficiency. Clin Nephrol 76(2):110–116

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nephrology Department, Inonu University Medical Faculty, 4400, Malatya, Turkey

    Hulya Taskapan

Authors
  1. Hulya Taskapan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hulya Taskapan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Taskapan, H. Is 24,25(OH)D level really high in dialysis patients with high FGF23 levels?. Int Urol Nephrol 44, 1135–1144 (2012). https://doi.org/10.1007/s11255-012-0157-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-012-0157-5

Keywords

Search

Navigation