25-26-dihydroxycholecalciferol and Kidney-Failure--Chronic

The circulating concentrations of 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D are abnormally low in patients with chronic renal failure (CRF). To determine the importance of substrate (25-hydroxyvitamin D) concentration in this phenomenon, five patients with end stage renal disease treated with hemodialysis were given 25-hydroxyvitamin D3 (25-OH-D3) orally for 4 weeks. The serum concentration of 25-OH-D3 increased from a mean (+/- SEM) of 26 +/- 5 ng/ml immediately before therapy to a maximum of 108 +/- 5 ng/ml 4 weeks after beginning administration of 25-OH-D3. The concentrations of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), 24,25-dihydroxyvitamin D3 (24,25(OH)2D3), and 25,26-dihydroxyvitamin D3 (25,26(OH)2D3) increased from 6.6 +/- 0.8 pg/ml, 0.29 +/- 0.10 ng/ml, and 0.36 +/- 0.06 ng/ml, respectively, immediately before 25-OH-D3 administration to 21.7 +/- 2.2 pg/ml, 0.48 +/- 0.09 ng/ml; and 0.78 +/- 0.12 ng/ml, respectively, after 4 weeks of administration of 25-OH-D3. These results suggest that substrate availability may be an important determinant of the circulating concentrations of these metabolites in patients with CRF. It seems possible that the therapeutic effects of 25-OH-D3 administration to the CRF patient may be mediated through the normal actions of 1,25-dihydroxyvitamin D3, 24,25-dihydroxyvitamin D3, and perhaps other metabolites rather than through analog effects of 25-OH-D3.

Topics: 24,25-Dihydroxyvitamin D 3; Administration, Oral; Calcifediol; Calcitriol; Dihydroxycholecalciferols; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis; Vitamin D

Here we report the use of newly developed and established techniques for the determination of plasma levels of a broad spectrum of vitamin D3 metabolites, including vitamin D3 and 25OHD3-lactone, in normal humans, chronic renal failure patients, and anephric subjects. The methodology described consisted of methanol-methylene chloride extraction, Lipidex-5000 chromatography with stepwise gradient elution, normal-phase HPLC with concave gradient elution, and sensitive ligand-binding assays. The results of the study strongly suggest an extrarenal source(s) for 24,25(OH)2D3 and 25,26(OH)2D3 and indicate that both 25OHD3-lactone and 1,25(OH)2D3 may be produced solely in the kidney of the human. Significant reductions or nondetectable plasma levels of vitamin D3 in the renal disease patients may reflect abnormalities in the hepatobiliary-intestinal and/or cutaneous metabolism of vitamin D.

Topics: 24,25-Dihydroxyvitamin D 3; Calcifediol; Calcitriol; Cholecalciferol; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Kidney Failure, Chronic; Methods; Nephrectomy