Summary
Twentytwo adult patients with chronic renal insufficiency received long-term treatment (mean 15.4 months) with 1-alpha-hydroxycholecalciferol (1α(OH)D3), a synthetic vitamin D analogue. Before treatment 73% of the patients were hypocalcemic, intestinal calcium absorption was reduced in 82%, serum immunoreactive parathyroid hormone (i-PTH) was increased in 86% and serum alkaline phosphatases were increased in 50% of them. Furthermore, 91% of the patients had generalized scintigraphic bone changes indicative of renal osteodystrophy, 59% had reduced bone mineral content (BMC), 32% had radiographic bone changes and 27% had clinical symptoms. During treatment all patients became normocalcemic within one month; intestinal calcium absorption increased to reach normal values; i-PTH declined significantly, but remained elevated in 50% of patients; serum alkaline phosphatases declined significantly and became normal in all except 2 patients; bone scintigraphy and/or radiography showed considerable improvement in 4 patients; the accelerated bone loss in uremia ceased and bone pain disappeared in 5 of the 6 patients who had had this symptom. Nineteen short-lasting acute hypercalcemic episodes were recorded during treatment. In all cases normocalcemia was re-established within 72 hours after discontinuing the drug. No side-effects were observed apart from hypercalcemia. The present data demonstrate the long-term beneficial effects of 1 α(OH)D3 in improving clinical symptoms and reversing several biochemical and skeletal abnormalities in patients with chronic renal failure.
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References
Almqvist, S., Hjern, B., Wästhed, B.: The diagnostic value of a radioimmunoassay for parathyroid hormone in human serum. Acta endocrinol.78, 493–509 (1975)
Bordier, P., Ryckwaertz, A., Marie P., Miravel, L., Norman, A. W., Rasmussen, H.: Vitamin D metabolites and bone mineralization in man. In: Vitamin D, biochemical, chemical and clinical aspects related to calcium metabolism. (ed. A. W. Norman et al.) pp. 897–911. Berlin, New York: Walter de Gruyter 1977
Brickman, A. S., Coburn, J. W., Norman, A. W.: Action of 1.25-dihydroxycholecalciferol, a potent, kidney-produced metabolite of vitamin D3, in uremic man. New Engl. J. Med.287, 891–895 (1972)
Brickman, A. S., Coburn, J. W., Massry, S. G., Norman, A. W.: 1.25 Dihydroxy-Vitamin D3 in normal man and patients with renal failure. Ann. int. Med.80, 161–168 (1974)
Brownjohn, A. M., Goodwin, F. J., Hately, W., Marsh, F. F., O'Riordan, J. L. H., Papapoulos, S. E.: 1-alpha-hydroxycholecalciferol for renal osteodystrophy. Br. med. J.1977/II, 721–723
Cameron, J. R., Sorenson, J. A.: Measurement of bone mineral in vivo: An improved method. Science142, 230–232 (1963)
Catto, G. R. D., MacLeod, M., Pelc, B., Kodicek, E.: 1α-hydroxycholecalciferol: A treatment for renal bone disease. Br. med. J.1975/I, 12–14
Chen, J. C., Castillo, L., Korycha-Dahl, M., DeLuca, H. F.: Role of vitamin D metabolites in phosphate transport of rat intestine. J. Nutr.104, 1056–1060 (1974)
Coburn, J. W., Brickman, A. S., Sherrard, D. J., Singer, F. R., Baylink, D. J., Wong, E. G. C., Massry, S. G., Norman, A. W.: Clinical efficacy of 1,25-dihydroxy-vitamin D3 in renal osteodystrophy. In: Vitamin D, biochemical, chemical and clinical aspects related to calcium metabolism (ed. A. W. Norman et al.) pp. 657–666. Berlin, New York: Walter de Gruyter 1977
Curtis, F. K., Fellows, H., Clayton, R.: Estimation of human calcium absorption by external radioisotope counting. J. Lab. clin. Med.69, 1036–1041 (1967)
DeLuca, H. F.: Vitamin D metabolism: Recent developments. Triangle12, 111–118 (1973)
Eastwood, J. B., Harris, E., Stamp, T. C. B., DeWardener, H. E.: Vitamin-D deficiency in the osteomalacia of chronic renal failure. Lancet1976/II, 1209–1211
Fournier, A. E., Arnaud, C. D., Johnson, W. J., Taylor, W. F., Goldsmith, R. S.: Etiology of hyperparathyroidism and bone disease during hemodialysis. Factors affecting serum immunoreactive parathyroid hormone. J. clin. Invest.50, 599–605 (1971)
Fraser, D. R., Kodicek, E.: Unique biosynthesis by kidney of a biologically active vitamin D metabolite. Nature228, 764–766 (1970)
Goldsmith, R. S., Furszyfer, J., Johnson, W. J., Fournier, A. E., Arnaud, C.D.: Control of secondary hyperparathyroidism during long-term hemodialysis. Am. J. Med.59, 692–699 (1971)
Haussler, M. R., McCain, T. A.: Basic and clinical concepts related to vitamin D metabolism and action. New Engl. J. Med.297, 974–983 (1977)
Henderson, R. G., Russell, R. G. G., Ledingham, J. G. G., Smith, R., Oliver, D. O., Walton, R. J., Small, D. G., Preston, C., Warner, G. T.: Effects of 1,25-dihydroxycholecalciferol on clacium absorption, muscle weakness, and bone disease in chronic renal failure. Lancet1974/I, 379–384
Holick, M. F., Semmler, E. J., Schnoes, H. K., DeLuca, H. F.: 1α-hydroxy derivative of vitamin D3: A highly potent analog of 1α,25-dihydroxyvitamin D3. Science180, 190–191 (1973)
Hruska, K. A., Kapelman, R., Rutherford, W. E., Klahr, S., Slatopolsky, E.: Metabolism of immunoreactive parathyroid hormone in the dog. The role of the kidney and the effects of chronic renal disease. J. clin. Invest.56, 39–48 (1975)
Katz, A. I., Hampers, C. L., Merrill, J. P.: Secondary hyperparathyroidism and renal osteodystrophy in chronic renal failure. Medicine48, 333–374 (1969)
Lumb, G. A., Mawer, E. B., Stanbury, S. W.: The apparent vitamin D resistance of chronic renal failure. Am. J. Med.50, 421–441 (1971)
Madsen, S., Ølgaard, K.: 1-Alpha-hydroxycholecalciferol treatment of adults with chronic renal failure. Acta med. scand.200, 1–5 (1976)
Madsen, S., Ølgaard, K.: Evaluation of a new, automatic calcium ion analyzer. Clin. Chem.23, 690–694 (1977a)
Madsen, S., Thaysen, J. H., Ølgaard, K., Heerfordt, J., Løkkegaard, H.: Is renal osteodystrophy reversible? A study in kidney transplanted patients after 1.5 years total withdrawal of prednisone. In: Proceedings of the European Dialysis and Transplant Association. Vol. 14 (ed. B. H. Robinson et al.) pp. 433–441. Tunbridge Wells: Pitman 1977b
Madsen, S., Ølgaard, K., Ladefoged, J.: Degree and course of skeletal demineralization in patients with chronic renal insufficiency. Scand. J. Urol. Nephrol. (In press 1977c)
Madsen, S.: Unpublished data (1977d)
Massry, S. G., Coburn, J. W.: Renal osteodystrophy. In: Clinical disorders of fluid and electrolyte metabolism (ed. M. H. Maxwell & C. R. Kleeman), pp. 505–539. New York: McGraw-Hill 1972.
Moorhead, J. F., Tatler, G. L. V., Baillod, R. A., Varghese, Z., Wills, M. R., Farrow, S. C.: Effects of age, sex and polycystic disease on progressive bone disease of renal failure. Br. med. J.1974/IV, 557–560
Naik, R. B., Gosling, P., Price, C. P., Robinson, B. H. B., Dabek, J. T., Heath, D. A., James, H. M., Kanis, J. A., Smith, R.: Wholebody in-vivo neutron activation analysis in assessing treatment of renal osteodystrophy with 1-alpha-hydroxy-cholecalciferol. Br. med. J.1976/II, 79–83
Ogg, C. S.: Parathyroidectomy in the treatment of secondary renal hyperparathyroidism. Kidney Int.4, 168–173 (1973)
Omdahl, J., Holick, M., Suda, T., DeLuca, H. F.: Biological activity of 1,25-dihydroxycholecalciferol. Biochemistry10, 2935–2940 (1971)
Peacock, M., Gallagher, J. C., Nordin, B. E. C.: Action of 1α-hydroxy vitamin D3 on calcium absorption and bone resorption in man. Lancet1974/I, 385–389
Pierides, A. M., Ellis, H. A., Simpson, W., Dewar, J. H., Ward, M. K., Kerr, D. N. S.: Variable response to long-term 1α-hydroxycholecalciferol in hemodialysis osteodystrophy. Lancet1976/I, 1092–1095
Ritz, E., Krempien, B., Mehls, O., Malluche, H.: Skeletal abnormalities in chronic renal insufficiency before and during maintenance hemodialysis. Kidney Int.4, 116–127 (1973)
Ritz, E., Clorius, J. H.: Scientigraphy in uremic bone disease. Nephron17, 321–324 (1976)
Rutherford, W. E., Bordier, P., Marie, P., Hruska, K., Harter, H., Greenwalt, A., Blondin, J., Haddad, J., Bricker, N., Slatopolsky, E.: Phosphate control and 25-hydroxycholecalciferol administration in preventing experimental renal osteodystrophy in the dog. J. clin. Invest.60, 332–341 (1977)
Tougaard, L., Sørensen, E., Brøckner-Mortensen, J., Christensen, M. S., Rødbro, P., Sørensen, A. W. S.: Controlled trial of 1α-hydroxycholecalciferol in chronic renal failure. Lancet1976/I, 1044–1047
Virchow, L.: Virch. Arch. pathol. Anat. Physiol. klin. Med.8, 103–106 (1855)
Witmer, G., Margolis, A., Fontaine, P., Fritsch, J., Lenoir, G., Broyer, M., Balsam, S.: Effects of 25-hydroxycholecalciferol on bone lesions of children with terminal renal failure. Kidney Int.10, 395–408 (1976)
Ølgaard, K., Heerfordt, J., Madsen, S.: Scientigraphic skeletal changes in uremic patients on regular hemodialysis. Nephron17, 325–334 (1976)
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Madsen, S., Ølgaard, K. Long-term trial of 1-alpha-hydroxycholecalciferol in adults with chronic renal failure. Eur J Clin Pharmacol 13, 401–408 (1978). https://doi.org/10.1007/BF00566316
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DOI: https://doi.org/10.1007/BF00566316