calcifediol-lactone and Kidney-Failure--Chronic

Metabolites of vitamin D3 were measured in the circulation of four patients on chronic haemodialysis (three of whom were surgically anephric) before and during daily ingestion of 40 000 i.u. of cholecalciferol. Circulating 24,25-dihydroxyvitamin D3 [24,25-(OH)2D3] was measurable, but abnormally low before treatment; its circulating concentration rose in a substrate dependent manner when serum 25-hydroxyvitamin D3 (25-OHD3) increased, but the response was reduced when compared with the normal relationship. Serum 1,25-hydroxyvitamin D3 [1,25-(OH)2D3] and calcidiol lactone (25-OHD3-lactone) were consistently unmeasurable in sera from these patients before administration of cholecalciferol. However, when serum 25-OHD3 rose with treatment, 1,25-(OH)2D3 became detectable in the sera of three of the four patients and 25-OHD3-lactone could be measured in all of them. These data indicate that extrarenal sites of synthesis of 24,25-(OH)2D3, 25-OHD3-lactone and 1,25-(OH)2D3 exist in chronically dialysed patients but require large amounts of substrate to be significant.

Topics: Adult; Calcifediol; Calcitriol; Chromatography, High Pressure Liquid; Dihydroxycholecalciferols; Female; Humans; Kidney Failure, Chronic; Middle Aged; Renal Dialysis; Statistics as Topic

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