Extra-renal production of 24,25-dihydroxyvitamin D in chronic renal failure during 25 hydroxyvitamn D3 therapy

J. E. Zerwekh, J. J. McPhaul, T. F. Parker, C. Y C Pak

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8 Scopus citations


To assess whether or not production of 24,25-dihydroxyvitamin D [24,25-(OH)2D] can occur in patients with renal failure, we administered 25-OHD3 (100 μg/day) to eight patients undergoing chronic hemodialysis, six of whom had intact kidneys (CRF) and two who were anephric. Prior to 25-OHD3 administration, serum 24,25-(OH)2D was undectable (UD), (<0.3 ng/ml) in all subjects except for one patient with CRF and one anephric subject in whom concentrations of 24,25-(OH)2D were 0.5 ng/ml and 1.5 ng/ml, respectively. The administration of 25-OHD3 (100 μg/day) for 8 weeks to six CRF and two anephric patients produced significant increases in serum 24,25-(OH)2D concentration, from UD to 2.9 ± 0.5 SEM ng/ml (p <0.0025) in CRF, and from 0.9 ± 0.4 ng/ml to 2.6 ± 0.8 ng/ml (P <0.005) in the anephric group. Serum 24,25-(OH)2D concentration was found to be correlated significantly with serum 25-OHD concentration (r = 0.93, P <0.01). Serum 1,25-(OH)2D did not change in anephric subjects but significantly increased in patients with CRF (9 ± 3 to 14 ± 3 pg/ml, P <0.05). Additional studies in seven normal subjects and seven anephric patients who received 1,25-(OH)2D (2 μg/day) for 8 days disclosed a significant increase in serum 24,25-(OH)2D in normals (2.4 ± 0.2 ng/ml to 3.3 ± 0.3 ng/ml, P <0.05) but not in the anephric humans. The data suggest that there is an impaired ability to bioproduce 24,25-(OH)2D in anephric humans or in CRF but that sufficient provision of the substrate (25-OHD3) may result in the extra-renal production of 24,25-(OH)2D. The extra-renal production of 24,25-(OH)2D does not appear to be regulated in comparable fashion to that on the renal enzyme, since 1,25-(OH)2D administration failed to raise 24,25-(OH)2D concentration in anephric subjects. Despite low serum 1,25-(OH)2D concentrations in patients with CRF, 25-OHD3 therapy may also raise 1,25-(OH)2D levels in some patients, suggesting the presence of residual 1α-hydroxylase activity.

Original languageEnglish (US)
Pages (from-to)401-406
Number of pages6
JournalKidney international
Issue number2
StatePublished - 1983

ASJC Scopus subject areas

  • Nephrology


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