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Pediatric Nephrology

, Volume 10, Issue 3, pp 331–336 | Cite as

Calcitriol administration in end-stage renal disease: intravenous or oral?

  • L. Darryl Quarles
  • Olafur Skuli Indridason
Review Article

Abstract

1,25-Dihydroxyvitamin D deficiency plays an important role in the pathogenesis of secondary hyperparathyroidism, and adequate replacement of this hormone is considered essential to normalize parathyroid gland function and restore bone homeostasis in patients with advanced renal failure. Although initial uncontrolled clinical trials suggested the superiority of intravenous calcitriol treatment, more recent controlled investigations show that different routes (oral versus intravenous), frequency (daily versus intermittent), and dosing (physiological versus pharmacological) of calcitriol administration are clinically equivalent. Overall, the response to calcitriol treatment depends more on the severity of secondary hyperparathyroidism and the presence of confounding variables, such as hyperphosphatemia and acquired abnormalities of parathyroid cell function, than the method of calcitriol administration.

Key words

End-stage renal disease Calcitriol Secondary hyperparathyroidism 

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References

  1. 1.
    Silver J (1992) Regulation of parathyroid hormone synthesis and secretion. In: Coe FL, Favus MJ (eds) Disorders of bone and mineral metabolism, Raven, New York, p 83Google Scholar
  2. 2.
    Pitts TO, Piraino BH, Mitro R, Chen TC, Segre GV, Greenberg A, Puschett JB (1988) Hyperparathyroidism and 1,25-dihydroxyvitamin D deficiency in mild, moderate, and severe renal failure. J Clin Endocrinol Metab 67: 876–881PubMedGoogle Scholar
  3. 3.
    Portale AA, Holloran BP, Murphy MM, Morris RC Jr (1986) Oral intake of phosphorus can determine the serum concentration of 1,25-dihydroxyvitamin D by determining its production rate in humans. J Clin Invest 77: 7–12PubMedGoogle Scholar
  4. 4.
    Lopez-Hilker S, Galceran T, Chan Y-L, Rapp N, Martin KJ, Slatopolsky E (1986) Hypocalcemia may not be essential for the development of secondary hyperparathyroidism in chronic renal failure. J Clin Invest 78: 1097PubMedGoogle Scholar
  5. 5.
    Reichel H, Szabo A, Uhl J, Pesian S, Schmutz A, Schmidt-Gayk H, Ritz E (1993) Intermittent versus continuous administration of 1,25-dihydroxyvitamin D3 in experimental hyperparathyroidism. Kidney Int 44: 1259–1265PubMedGoogle Scholar
  6. 6.
    Patel SR, Ke HQ, Vanholder R, Hsu CH (1994) Inhibition of nuclear uptake of calcitriol receptor by uremic ultrafiltrate. Kidney Int 46: 129–133PubMedGoogle Scholar
  7. 7.
    Patel SR, Ke HQ, Hsu CH (1994) Regulation of calcitriol receptor and its mRNA in normal and renal failure rats. Kidney Int 45: 1020–1027PubMedGoogle Scholar
  8. 8.
    Koyama H, Nishizawa Y, Inaba M, Hino M, Drahl JM, Deluca HF, Morii H (1994) Impaired homologous upregulation of vitamin D receptor in rats with chronic renal failure. Am J Physiol 266: F706-F712PubMedGoogle Scholar
  9. 9.
    Fukuda N, Tanaka H, Tominaga Y, Fukagawa M, Kurokawa K, Seino Y (1993) Decreased 1,25-dihydroxyvitamin D3 receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients. J Clin Invest 92: 1436–1443PubMedGoogle Scholar
  10. 10.
    Brown A, Dusso A, Slatopolsky E (1992) Vitamin D. In: Seldin DW, Giebisch G (eds) The kidney: physiology and pathophysiology, 2nd edn. Raven, New York, pp 1505–1552Google Scholar
  11. 11.
    Salusky IB, Goodman WG, Horst R, Segre GV, Kim L, Norris KC, Adams JS, Holloway M, Fine RN, Coburn JW (1990) Pharmacokinetics of calcitriol in continuous ambulatory and cycling peritoneal dialysis patients. Am J Kidney Dis 16: 126–132PubMedGoogle Scholar
  12. 12.
    Quarles LD, Yohay DA, Carroll BA, Spritzer CE, Minda SA, Bartholomay D, Lobaugh BA (1994) Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD. Kidney Int 45: 1710–1721PubMedGoogle Scholar
  13. 13.
    Joffe P, Cintin C, Ladefoged SD, Rasmussen SN (1994) Pharmacokinetics of 1α-hydroxycholecalciferol after intraperitoneal, intravenous and oral administration in patients undergoing peritoneal dialysis. Clin Nephrol 41: 364–369PubMedGoogle Scholar
  14. 14.
    Nagant de Deuxchaisnes C, Devogelaer JP, De Nayer P (1990) Comparison of 1,25-(OH)2D3 levels after the administration of calcitriol and alfacalcidol. In: Vitamin D gene regulation structure — function analysis and clinical application. Proceedings of the Eighth Workshop on Vitamin D, Paris, France. DeGruyter, Berlin, New York, pp 314–315Google Scholar
  15. 15.
    Galbraith SC, Quarles LD (1993) Tertiary/refractory secondary hyperparathyroidism. In: Favus MJ (ed) Primer on the metabolic bone diseases and disorders of mineral metabolism, 2nd edn. Raven, New York, pp 159–163Google Scholar
  16. 16.
    Krause MW, Hedinger CE (1985) Pathologic study of parathyroid glands in tertiary hyperparathyroidism. Hum Pathol 16: 772–784PubMedGoogle Scholar
  17. 17.
    Arnold A, Brown MF, Urena P, Gas RD, Sarfati E, Drueke TB (1995) Monoclonality of parathyroid tumors in chronic renal failure and primary parathyroid hyperplasia. J Clin Invest 95: 2047PubMedGoogle Scholar
  18. 18.
    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 Ca2+-sensing receptor from bovine parathyroid. Nature 366: 575–580PubMedGoogle Scholar
  19. 19.
    Gogusev J, Duchambon P, Giovannini M, Sarfati E, Drueke TB (1996) Expression in pathologic parathyroid gland tissue of calcium receptor (CaR) and vitamin D receptor (VDR) gene message (mRNA). J Am Soc Nephrol 6: 961Google Scholar
  20. 20.
    Garrett JE, Capuano IV, Hammerland LG, Hung BCP, Brown EM, Hebert SC, Nemeth EF, Fuller F (1995) Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs. J Biol Chem 270: 12919–12925PubMedGoogle Scholar
  21. 21.
    Hernandez AY, Torregrosa A, Campistol TV, Rodriguez TA, Nefrologia MS (1995) High phosphorus directly stimulates PTH secretion by human parathyroid tissue (abstract). J Am Soc Nephrol 6: 957Google Scholar
  22. 22.
    Slatopolsky E, Weerts C, Thielan J, Horst R, Harter H, Martin KJ (1984) Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxycholecalciferol in uremic patients. J Clin Invest 74: 2136–2143PubMedGoogle Scholar
  23. 23.
    Andress DL, Norris KC, Coburn JW, Slatopolsky EA, Sherrard DJ (1989) Intravenous calcitriol in the treatment of refractory osteitis fibrosa of chronic renal failure. N Engl J Med 321: 274–279PubMedGoogle Scholar
  24. 24.
    Quarles LD, Davidai GA, Schwab SJ, Bartholomay DW, Lobaugh B (1988) Oral calcitriol and calcium: efficient therapy for uremic hyperparathyroidism. Kidney Int 34: 840–844PubMedGoogle Scholar
  25. 25.
    Oettinger CW, Oliver JC, Macon EJ (1992) The effects of calcium carbonate as the sole phosphate binder in combination with low calcium dialysate and calcitriol therapy in chronic hemodialysis patients. J Am Soc Nephrol 3: 995–1001PubMedGoogle Scholar
  26. 26.
    Mazzaferro S, Pasquali M, Ballanti P, Bonucci E, SiDanza P, Sardella D, Taggi F, Coen G (1994) Intravenous versus oral calcitriol therapy in renal osteodystrophy: results of a prospective, pulsed and dise-comparable study. Miner Electrolyte Metab 20: 122–129PubMedGoogle Scholar
  27. 27.
    Coburn JW, Salusky IB, Norris KC, Goodman WG (1991) Oral and parenteral calcitriol for the management of end-stage renal disease. Contrib Nephrol 90: 166–182PubMedGoogle Scholar
  28. 28.
    Kiss D, Kraenzlin M (1994) Comparison of pulse intravenous (IV) versus oral (PO) calcitriol treatment of secondary hyperparathyroidism (HPT) in chronic hemodialysis patients (HD PTS) (abstract). J Am Soc Nephrol 5: 883Google Scholar
  29. 29.
    Rosenkranz AR, Thalhammer F, Holub, Novacek G, Traindl O (1994) Calcitriol — daily oral or intravenous pulse therapy (abstract). J Am Soc Nephrol 5: 887Google Scholar
  30. 30.
    Goggins MO, Rao DS, Bhat S, Zasuwa G, Narins RG (1994) Hyperphosphatemia predicts a poor response to I.V. calcitriol (IVC) in hemodialysis (HD) patients (abstract) J Am Soc Nephrol 5: 879Google Scholar
  31. 31.
    Faugere M-C, Friedler RM, Malluche HH (1993) Efficacy and limitations of pulse I.V. and pulse oral 1,25 vit D therapy on bone disease in patients on chronic dialysis (abstract). J Am Soc Nephrol 4: 695Google Scholar
  32. 32.
    Song MM, Levine BS (1994) Oral pulse calcitriol versus intravenous calcitriol therapy in treatment of hyperparathyroidism in hemodialysis patients (abstract). J Am Soc Nephrol 5: 889Google Scholar
  33. 33.
    Fischer ER, Harris DC (1993) Comparison of intermittent oral and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism. Clin Nephrol 40: 216–220PubMedGoogle Scholar
  34. 34.
    Lee WT, Padayachi K, Collins JF, Cundy T (1994) A comparison of oral and intravenous alfacalcidol in the treatment of uremic hyperparathyroidism. J Am Soc Nephrol 5: 1344–1348PubMedGoogle Scholar
  35. 35.
    Hamdy NAT, Kanis JA, Benton MNC, Brown CB, Juttman JR, Jordans JGM, Josse S, Meyrier A, Lins RL, Fairey IT (1995) Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure. BMJ 310: 358–363PubMedGoogle Scholar
  36. 36.
    Herrman P, Ritz E, Schmidt-Gayk H, Schafer I, Geyer J, Nonnast-Daniel B, Koch KM, Weber U, Horl W, Haas-Worle A (1994) Comparison of intermittent and continuous oral administration of calcitriol in dialysis patients: a randomized prospective trial. Nephron 67: 48–53PubMedGoogle Scholar
  37. 37.
    Moe S, Kraus M, Gassensmith C, Gannon F, North J, Peacock M (1994) A randomized trial of pulse versus daily oral calcitriol in CAPD patients (abstract). J Am Soc Nephrol 5: 854Google Scholar
  38. 38.
    Liou H-H, Chiang S-S, Huang TP, Shieh SD, Akmal M (1994) Comparative effect of oral or intravenous calcitriol on secondary hyperparathyroidism in chronic hemodialysis patients. Miner Electrolyte Metab 20: 97–102PubMedGoogle Scholar
  39. 39.
    Cannella G, Bonucci E, Rolla D, Ballanti P, Moriero E, Grandi RD, Augeri C, Claudiani F, Maio GD (1994) Evidence of healing of secondary hyperparathyroidism in chronically hemodialyzed uremic patients treated with long-term intravenous calcitriol. Kidney Int 46: 1124PubMedGoogle Scholar
  40. 40.
    Fukagawa M, Okazaki R, Takano K, Kaname S-Y, Ogata E, Kitaoka M, Harada S-I, Sekine N, Matsumoto T, Kurokawa K (1990) Regression of parathyroid hyperplasia by calcitriol-pulse therapy in patients on long-term dialysis. N Engl J Med 323: 421PubMedGoogle Scholar
  41. 41.
    Szabo A, Merke J, Beier E, Mall G, Ritz E (1989) 1,25(OH)2 Vitamin D3 inhibits parathyroid cell proliferation in experimental uremia. Kidney Int 35: 1049–1056PubMedGoogle Scholar
  42. 42.
    Goodman WB, Ramirez JA, Belin TR, Chon Y, Gales B, Segre GV, Salusky IB (1994) Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy, Kidney Int 46: 1160PubMedGoogle Scholar

Copyright information

© IPNA 1996

Authors and Affiliations

  • L. Darryl Quarles
    • 1
  • Olafur Skuli Indridason
    • 1
  1. 1.Duke University Medical CenterDurhamUSA

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