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October 6, 1975, Vol 234, No. 1 >
ARTICLE | October 6, 1975

1-a-Hydroxyvitamin D3 in Chronic Renal Failure: Title and subTitle BreakA Potent Analogue of the Kidney Hormone, 1,25-Dihydroxycholecalciferol FREE

James C. M. Chan, MD; Susan B. Oldham, PhD; Michael F. Holick, PhD; Hector F. DeLuca, PhD
[+] Author Affiliations

Read in part before the 44th annual meeting of the Society for Pediatric Research, Washington, DC, May 3, 1974; the Third International Symposium of Pediatric Nephrology, Washington, DC, Oct 1, 1974; and the 14th International Congress of Pediatrics, Buenos Aires, Oct 5, 1974.

Reprint requests to Department of Nephrology, Children's Hospital National Medical Center, 2125 Thirteenth St NW, Washington, DC 20009 (Dr. Chan).


JAMA. 1975;234(1):47-52. doi:10.1001/jama.1975.03260140049013
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References

In chronic renal disease, the synthesis of the kidney hormone, 1,25-dihydroxyvitamin D3 (1,25-[OH]2D3), is impaired, thus contributing to the development of renal osteodystrophy. The clinical use of 1,25-[OH]2D3 is limited, due to the complexity and expense of its chemical synthesis.

This study reports the use of 1-α-hydroxyvitamin D3 (1-α-OH-D3), an active analogue of (1,25-[OH]2D3, in eight patients with chronic renal failure, five of whom were undergoing long-term hemodialysis. The drug was given orally for 6 to 260 days at a dosage of 1μg to 4μg/day. Short-term (21 days) balance studies showed an increase in intestinal calcium absorption and a simultaneous fall in serum parathyroid hormone levels during administration of 1-α-OH-D3. In two long-term studies (160 and 260 days), roentgenographic improvement of renal osteodystrophy was seen after 45 and 185 days, respectively.

The data indicate that 1-α-OH-D3 holds considerable promise for the prevention and treatment of renal osteodystrophy.

(JAMA 234:47-52, 1975)

REFERENCES

1 +
DeLuca HF:  The kidney as an endocrine organ for the production of 1,25-dihydroxyvitamin D3, a calcium-mobilizing-hormone . N Engl J Med 289:359-365, 1973;.
2 +
Coburn JW, Norman AW:  Role of the kidney in the metabolism of calciferol (vitamin D) . Clin Nephrol 1:273-280, 1973;.
3 +
Fraser DR, Kodicek E:  Unique biosynthesis by kidney of a biologically active vitamin D metabolite . Nature 228:764-766, 1970;.
4 +
Brickman AS, Coburn JW, Norman AW:  Action of 1,25-dihydroxycholecalciferol, a potent, kidney-produced metabolite of vitamin D3, in uremic man . N Engl J Med 287:891-894, 1972;.
5 +
Henderson RG, Russell RGG, Ledingham JFF, et al:  Effects of 1,25-dihydroxycholecalciferol on calcium absorption, muscle weakness, and bone disease in chronic renal failure . Lancet 1:379-384, 1974;.
6 +
Chan JCM, Beale MG, Albert MS:  Therapeutic implications of vitamin D metabolites . Clin Proc Child Hosp Natl Med Center 39:59-63, 1974;.
7 +
Holick MF, Semmler EJ, Schnoes HK, et al:  1 alpha-hydroxy derivative of vitamin D3: A highly potent analog of 1,25-dihydroxyvitamin D3 . Science 180:190-191, 1973;.
8 +
Semmler EG, Holick MS, Schnoes HK, et al:  Synthesis of 1 alpha, 25-dihydroxycholecalciferol—a metabolically active form of vitamin D3 . Tetrahedron Lett 40:4147-4150, 1972;.
9 +
Chalmers TM, Hunter JO, Davie MW, et al:  1 alpha-hydroxycholecalciferol as a substitute for the kidney hormone 1,25-dihydroxycholecalciferol in chronic renal failure . Lancet 2:696-699, 1973;.
10 +
Chan JCM:  The effect of milk formulae on acid balance . Nutr Metab 16:140-154, 1974;.
11 +
Chan JCM:  Dietary management of renal failure in infants and children: Principle of nutritional therapy and some representative diets . Clin Pediatr 12:707-713, 1973;.
12 +
Arnaud CD, Tsao HS, Littledike ET:  Radioimmunoassay of human parathyroid hormone in serum . J Clin Invest 50:21-34, 1971;.
13 +
Shaw JW, Oldham SB, Bethune JE, et al:  Parathyroid hormone (PTH)-mediated rise in urinary cyclic AMP (UcAMP) during acute extracellular fluid (ECF) expansion natriuresis in man . J Clin Endocrinol Metab 39:311-315, 1974;.
14 +
Arnaud CD, Sizemore GW, Oldham SB, et al:  Human parathyroid hormone, glandular and secreted molecular species . Am J Med 50:630-638, 1971;.
15 +
Peacock M, Callagher JC, Nordin BEC:  Action of 1 alpha-hydroxyvitamin D, on calcium absorption and bone resorption in man . Lancet 1:385-389, 1974;.
16 +
Bordier P, Pechet MM, Hesse R, et al:  Response of adult patients with osteomalacia to treatment with crystalline 1 alpha-hydroxy vitamin D3 . N Engl J Med 291:866-870, 1974;.
17 +
Oldham SB, Arnaud CD, Jowsey J: Endocrinology (Proceedings of the Fourth International Symposium) . London, William Neinemann Medical Books, Ltd, 1973;.

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1 +
DeLuca HF:  The kidney as an endocrine organ for the production of 1,25-dihydroxyvitamin D3, a calcium-mobilizing-hormone . N Engl J Med 289:359-365, 1973;.
2 +
Coburn JW, Norman AW:  Role of the kidney in the metabolism of calciferol (vitamin D) . Clin Nephrol 1:273-280, 1973;.
3 +
Fraser DR, Kodicek E:  Unique biosynthesis by kidney of a biologically active vitamin D metabolite . Nature 228:764-766, 1970;.
4 +
Brickman AS, Coburn JW, Norman AW:  Action of 1,25-dihydroxycholecalciferol, a potent, kidney-produced metabolite of vitamin D3, in uremic man . N Engl J Med 287:891-894, 1972;.
5 +
Henderson RG, Russell RGG, Ledingham JFF, et al:  Effects of 1,25-dihydroxycholecalciferol on calcium absorption, muscle weakness, and bone disease in chronic renal failure . Lancet 1:379-384, 1974;.
6 +
Chan JCM, Beale MG, Albert MS:  Therapeutic implications of vitamin D metabolites . Clin Proc Child Hosp Natl Med Center 39:59-63, 1974;.
7 +
Holick MF, Semmler EJ, Schnoes HK, et al:  1 alpha-hydroxy derivative of vitamin D3: A highly potent analog of 1,25-dihydroxyvitamin D3 . Science 180:190-191, 1973;.
8 +
Semmler EG, Holick MS, Schnoes HK, et al:  Synthesis of 1 alpha, 25-dihydroxycholecalciferol—a metabolically active form of vitamin D3 . Tetrahedron Lett 40:4147-4150, 1972;.
9 +
Chalmers TM, Hunter JO, Davie MW, et al:  1 alpha-hydroxycholecalciferol as a substitute for the kidney hormone 1,25-dihydroxycholecalciferol in chronic renal failure . Lancet 2:696-699, 1973;.
10 +
Chan JCM:  The effect of milk formulae on acid balance . Nutr Metab 16:140-154, 1974;.
11 +
Chan JCM:  Dietary management of renal failure in infants and children: Principle of nutritional therapy and some representative diets . Clin Pediatr 12:707-713, 1973;.
12 +
Arnaud CD, Tsao HS, Littledike ET:  Radioimmunoassay of human parathyroid hormone in serum . J Clin Invest 50:21-34, 1971;.
13 +
Shaw JW, Oldham SB, Bethune JE, et al:  Parathyroid hormone (PTH)-mediated rise in urinary cyclic AMP (UcAMP) during acute extracellular fluid (ECF) expansion natriuresis in man . J Clin Endocrinol Metab 39:311-315, 1974;.
14 +
Arnaud CD, Sizemore GW, Oldham SB, et al:  Human parathyroid hormone, glandular and secreted molecular species . Am J Med 50:630-638, 1971;.
15 +
Peacock M, Callagher JC, Nordin BEC:  Action of 1 alpha-hydroxyvitamin D, on calcium absorption and bone resorption in man . Lancet 1:385-389, 1974;.
16 +
Bordier P, Pechet MM, Hesse R, et al:  Response of adult patients with osteomalacia to treatment with crystalline 1 alpha-hydroxy vitamin D3 . N Engl J Med 291:866-870, 1974;.
17 +
Oldham SB, Arnaud CD, Jowsey J: Endocrinology (Proceedings of the Fourth International Symposium) . London, William Neinemann Medical Books, Ltd, 1973;.

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