Clinical Investigation

Kidney International (1989) 35, 661–669; doi:10.1038/ki.1989.36

1,25(OH)2D3 administration in moderate renal failure: A prospective double-blind trial

Laurence R I Baker, S M Louise Abrams, Christopher J Roe, Marie-Claude Faugere, Paolo Fanti, Yahya Subayti and Hartmut H Malluche

Departments of Nephrology and Clinical Pharmacology, St. Bartholomew's Hospital, London, United Kingdom and Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky Medical Center, Lexington, Kentucky, USA

Correspondence: Hartmut H Malluche MD, Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky Medical Center, 800 Rose Street, Lexington, Kentucky 40536-0084, USA.

Received 18 February 1988; Revised 15 July 1988.

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Abstract

1,25(OH)2D3 administration in moderate renal failure: A prospective double blind trial. This study represents the first randomized prospective, double-blind, placebo-controlled trial of the efficacy of 1,25(OH)2D3 on bone histology and serum biochemistry in patients with mild to moderate renal failure. Sixteen patients with chronic renal impairment (creatinine clearance 20 to 59 ml per min) received either 1,25(OH)2D3, at a dose of 0.25 to 0.5 microg daily (eight patients), or placebo. Transiliac crest bone biopsies were performed before entrance into the study and after 12 months of experimental observation. None of the patients were symptomatic or had radiological evidence of bone disease. Of the thirteen patients who completed the study, initial serum 1,25(OH)2D levels were low in seven patients and parathyroid hormone levels were elevated in seven patients. Bone histology was abnormal in all patients. 1,25(OH)2D3 treatment was associated with a significant fall in serum phosphorus and alkaline phosphatase concentrations as well as with histological evidence of an amelioration of hyperparathyroid changes. In contrast to previous reports, no deterioration of renal function attributable to the treatment occurred, perhaps because a modest dose of 1,25(OH)2D3 was employed combined with meticulous monitoring. Further investigation is required to determine whether alternative therapeutic strategies (smaller doses or intermittent therapy) may avoid the potential for suppressing bone turnover to abnormally low levels in the long term.

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References

  1. Memmos DE, Eastwood JB, Talner LB, Gower PE, Curtis JR, Phillips ME, Carter GD, Alaghband-Zadeh J, Roberts AP, De Wardener HE: Double-blind trial of oral 1,25-dihydroxy vitamin D versus placebo in asymptomatic hyperparathyroidism in patients receiving maintenance haemodialysis. Br Med J 282:1919–1924, 1981
  2. Baker LRI, Muir JW, Sharman VL, Abrams SML, Greenwood RN, Cattell WR, Goodwin FJ, Marsh FP, Adami S, Hately W, Hattersley LA, Morgan AG, Papapoulos SE, Revell PA, Tucker AK, Chaput de Saintonge DM, O'Riordan JLH: Controlled trial of calcitriol in haemodialysis patients. Clin Nephrol 26:185–191, 1986
  3. Malluche HH, Ritz E, Lange HP, Kutschera K, Hodgson M, Seiffert U, Schoeppe W: Bone histology in incipient and advanced renal failure. Kidney Int 9:355–362, 1976 | PubMed | ISI | ChemPort |
  4. Malluche HH, Ritz E, Kutschera J, Krause K, Werner E, Gati A, Seiffert U, Lange HP: Calcium metabolism and impaired mineralization in various stages of renal insufficiency, in Vitamin D and Problems Related to Uremic Bone Disease, edited by Norman, Schaefer, Grigoleit, Herrath, Ritz, Berlin-New York, Walter de Gruyter, 1975, pp. 513–522
  5. Malluche HH, Werner E, Ritz E: Intestinal absorption of calcium and whole-body calcium retention in incipient and advanced renal failure. Miner Electrol Metabol 1:263–270, 1978
  6. Slatopolsky E, Gray R, Adams ND, Lewis J, Hruska K, Martin K, Klahr S, DeLuca H, Lemann J: Low serum levels of 1,25(OH)2D3 are not responsible for the development of secondary hyperparathyroidism in early renal failure. Kidney Int 14:733, 1978
  7. Ogura Y, Kawaguchi Y, Sakai S, Yamamoto M, Kimura Y, Oda Y, Imanura N, Tsukui I: Plasma levels of vitamin D metabolite in renal disease. Contrib Nephrol 22:18–27, 1980
  8. Cheung AK, Manolagas SC, Catherwood BD, Mosely CA, Mitas JA, Blantz RC, Deftos LJ: Determinants of serum 1,25(OH)2D levels in renal disease. Kidney Int 24:104–109, 1983 | PubMed | ISI | ChemPort |
  9. Portale AA, Booth BE, Tsai H, Morris RC: Reduced plasma concentration of 1,25 dihydroxyvitamin D in children with moderate renal insufficiency. Kidney Int 21:627–632, 1982 | PubMed | ISI | ChemPort |
  10. Wilson L, Felsenfeld A, Drezner MK, Llach F: Altered divalent ion metabolism in early renal failure: Role of 1,25(OH)2D. Kidney Int 27:565–573, 1985 | Article | PubMed | ISI | ChemPort |
  11. Lucas PA, Brown RC, Jones CR, Woodhead JS, Coles GA: Reduced 1,25(OH)2D3 may be responsible for the development of hyperparathyroidism in early chronic renal failure. Proc EDTA 22:1124–1128, 1985
  12. Ritz E, Malluche HH, Krempien B, Tschoepe W, Massry SG: Pathogenesis of renal osteodystrophy: Roles of phosphate and skeletal resistance to PTH, in Homeostasis of Phosphate and Other Minerals, edited by Massy SG, Ritz E, Rapado A, New York, Plenum Publishing Corp., 1978, pp. 423–436
  13. Christiansen C, Rodbro P, Christiansen MS, Hartnack B, Transbol I: Deterioration of renal function during treatment of chronic renal failure with 1,25-dihydroxycholecalciferol. Lancet ii:700–703, 1978
  14. INC Immuno Nuclear Reference Manual—Methods and Reagents of Immuno Nuclear Corporation, 1981, pp. 25–28
  15. Malluche HH, Faugere MC, Fanti P, Friedler RM: Calcitriol, parathyroid hormone and the accumulation of aluminum in bone in dogs with renal failure. J Clin Invest 79:754–761, 1987
  16. Reinhardt TA, Horst RL, Orf JW, Hollis BW: A microassay for 1,25-dihydroxy vitamin D not requiring high performance liquid chromatography: Application to clinical studies. J Clin Endocrinol Metab 58:91–98, 1984 | PubMed | ISI | ChemPort |
  17. Bikle DD: Assay of Calcium Regulating Hormones. New York, Springer-Verlag Publisher, 1983
  18. Malluche HH, Faugere MC: Mineralized Bone Histology. New York, S. Karger, 1986
  19. Lillie PD, Fullmer HM: Histopathologic technique and practical histochemistry. Fourth edition, New York, McGraw-Hill Book Co., 1976
  20. Malluche HH, Sherman D, Meyer W, Massry SG: A new semiautomatic method for quantitative static and dynamic bone histology. Calcif Tissue Int 34:439–448, 1982 | PubMed | ISI | ChemPort |
  21. Healy MD, Malluche HH, Goldstein DA, Singer FR, Massry ST: Effects of long-term therapy with calcitriol in patients with moderate renal failure. Arch Intern Med 14:1030–1033, 1980
  22. Massry SG, Gruber H, Rizvi AS, Sherman D, Goldstein DA, Letteri JM: Use of 1,25(OH)2D3 in the treatment of renal osteodystrophy in patients with moderate renal failure, (abstract) in Clinical Disorders of Bone and Mineral Metabolism edited by Frame B, Potts JR, Amsterdam, Excerpta Medica, 1983, pp. 260–262
  23. Malluche HH, Matthews C, Faugere MC, Fanti P, Friedler RM: 1,25-Dihydroxyvitamin D maintains bone cell activity, and parathyroid hormone modulates bone cell number in dogs. Endocrinology 119:1298–1304, 1986 | PubMed | ISI | ChemPort |
  24. Merke J, Klaus G, Hugel U, Waldherr R, Ritz E: No 1,25-dihydroxyvitamin D3 receptors on osteoclasts of calcium-deficient chicken despite demonstrable receptors on circulating monocytes. J Clin Invest 77:312–314, 1987
  25. Levine BS, Singer FR, Boycwe GH, Mallon JP, Miller ON, Coburn JW: Pharmacokinetics and biologic effects of calcitriol in normal humans. J Lab Clin Med 105:239–246, 1985
  26. Siede WH, Seiffert UB, Bundschuh F, Malluche HH, Schoeppe W: Alkaline phosphatase bone isoenzyme activity in serum in various degrees of micromorphometrically assessed renal osteopathy. Clin Nephrol 13:277–281, 1980 | PubMed | ISI | ChemPort |
  27. Coen G, Mazzaferro S, Bonucci E, Taggi F, Vallanti P, Binachi AR, Donato G, Massimetti C, Smacchi A, Cinotti GA: Bone GLA protein in predialysis chronic renal failure. Effects of 1,25(OH)2D3 administration in long-term follow-up. Kidney Int 28:783–790, 1985 | PubMed | ISI | ChemPort |
  28. Christiansen C, Rodbro P, Christensen MS, Hartnack B: Is 1,25 dihydroxycholecalciferal harmful to renal function in patients with chronic renal failure. Clin Endocrinol 15:229–236, 1981
  29. Smith AJ, Faugere MC, Abreo K, Fanti P, Julian B, Malluche HH: Aluminum related bone disease in mild and advanced renal failure. Am J Nephrol 6:275–283, 1986 | PubMed | ISI | ChemPort |
  30. Tougaard L, Sorensen E, Borchner-Mortensen J, Christensen MS, Rodbro P, Sorensen AWS: Controlled trial of 1 alpha-hydroxycholecalciferol in chronic renal failure. Lancet i:1044–1047, 1976
  31. Nordal KP, Dahl E, Halfe J, Thomassen Y, Aaseth J: Calcitriol treatment does not increase the serum aluminium concentration in patients with moderate renal failure. Acta Pharmacol Toxicol 59:293–295, 1986
  32. Paterson CR: Vitamin D poisoning: Survey of causes in 21 patients with hypercalcaemia. Lancet i:1164–1165, 1980

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