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

Extra-renal production of 24,25-dihydroxyvitamin D in chronic renal failure during 25 hydroxyvitamin D 3 therapy. To assess whether or not production of 24,25-dihydroxyvitamin D [24,25-(OH) 2 D] can occur in patients with renal failure, we administered 25-OHD 3 (100 µg/day) to eight patients undergoing chronic hemodialysis, six of whom had intact kidneys (CRF) and two who were anephric. Prior to 25-OHD 3 administration, serum 24,25-(OH) 2 D was undetectable (UD), ( 2 D were 0.5 ng/ml and 1.5 ng/ml, respectively. The administration of 25-OHD 3 (100 µg/day) for 8 weeks to six CRF and two anephric patients produced significant increases in serum 24,25-(OH) 2 D concentration, from UD to 2.9 ± 0.5 SEM ng/ml (P 2 D concentration was found to be correlated significantly with serum 25-OHD concentration (r = 0.93, P 2 D did not change in anephric subjects but significantly increased in patients with CRF (9 ± 3 to 14 ± 3 pg/ml, P 2 D (2 µg/day) for 8 days disclosed a significant increase in serum 24,25-(OH) 2 D in normals (2.4 ± 0.2 ng/ml to 3.3 ± 0.3 ng/ml, P 2 D in anephric humans or in CRF, but that sufficient provision of the substrate (25-OHD 3 ) may result in the extra-renal production of 24,25-(OH) 2 D. The extra-renal production of 24,25-(OH) 2 D does not appear to be regulated in a comparable fashion to that of the renal enzyme, since 1,25-(OH) 2 D administration failed to raise 24,25-(OH) 2 D concentration in anephric subjects. Despite low serum 1,25-(OH) 2 D concentrations in patients with CRF, 25-OHD 3 therapy may also raise 1,25-(OH) 2 D levels in some patients, suggesting the presence of residual 1α-hydroxylase activity. La production extra-renale de 24,25-dihydroxyvitamine dans l'insuffisance renale chronique pendant un traitement par la 25-hydroxyvitamine D 3 . Afin de determiner si la production de 24,25-dihydroxyvitamine D [24,25-(OH) 2 D] peut avoir lieu chez des malades en insuffisance renale chronique, nous avons administre de la 25-OHD 3 (100 µg/jour) a huit malades en hemodialyse chronique, dont six avaient des reins intacts (CRF) et deux etaient anephriques. Avant l'administration de 25-OHD 3 , la 24,25-(OH) 2 D serique etait indetectable (UD), ( 2 D etaient de 0,5 ng/ml et de 1,5 ng/ml, respectivement. L'administration de 25-OHD 3 (100 µg/jour) pendant 6 semaines a six malades CRF et deux anephriques a entraine des augmentations significatives de la concentration serique de 24,25-(OH) 2 D, passant de UD a 2,9 ± 0,5 SEM ng/ml (P 2 D a ete trouvee significativement correlee a la concentration serique de 25-OHD (r = 0,93, P 2 D serique n'a pas change chez les sujets anephriques, mais s'est significativement elevee chez les malades CRF (de 9 ± 3 a 14 ± 3 pg/ml, P 2 D (2 µg/jour) pendant huit jours ont revele une augmentation significative de la 24,25-(OH) 2 D serique chez les normaux (2,4 ± 0,2 ng/ml a 3,3 ± 0,3 ng/ml, P 2 D chez des hommes anephriques ou CRF, mais qu'un apport suffisant du substrat (25-OHD 3 ) peut entrainer une production extrarenale de 24,25-(OH) 2 D. La production extra-renale de 24,25-(OH) 2 D ne parait pas soumise a la meme regulation que l'enzyme renale, puisque l'administration de 1,25-(OH) 2 D n'a pas permis d'augmenter la concentration de 24,25-(OH) 2 D chez des sujets anephriques. Malgre de faibles concentrations de 1,25-(OH) 2 D chez les malades avec CRF, le traitement par la 25-OHD 3 peut egalement elever le niveau de 1,25-(OH) 2 D chez certains malades, suggerant la presence d'une activite 1α-hydroxylase residuelle.