Evidence for extrarenal production of 1α,25-dihydroxyvitamin D in man

Abstract

Recent studies provide evidence for extrarenal production of 1α,25-dihydroxyvitamin D [1α,25(OH)2D]. To investigate this possibility, serum vitamin D, 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1α,25(OH)2D were measured in eight adult anephric subjects. All were undergoing hemodialysis and three of them were receiving vitamin D, 50,000 or 100,000 U/d. Serum vitamin D was elevated in two of the patients given vitamin D and was abnormally low in the others. Mean serum 25-OHD was increased in patients given vitamin D (94.0 ± 7.6 ng/ml) and was normal in the others (16.4 ± 0.9 ng/ml, P<0.001). Mean serum 24,25(OH)2D was normal in patients given vitamin D (1.38 ± 0.27 ng/ml) and was low in the others (0.25 ± 0.08 ng/ml, P<0.001). Serum 24,25(OH)2D correlated significantly with serum 25-OHD (r=0.848, P<0.01). Mean serum 1α,25(OH)2D determined by receptor assay was 5.8 ± 1.9 pg/ml in patients who were not given vitamin D and was 14.1 ± 0.6 in those who were given vitamin D (P<0.001). Serum 1α,25(OH)2D correlated significantly with serum 25-OHD (r=0.911, P<0.01). Mean serum 1α,25(OH)2D, measured by bioassay, was 8.3 ± 1.9 pg/ml in patients who were not given vitamin D and was 15.9 ± 2.4 pg/ml in those who were given vitamin D (P<0.05). There was a significant correlation between the values for serum 1α,25(OH)2D obtained with the two methods (r=0.728, P<0.01). The results (a) provide evidence in man for extrarenal production of both 24,25(OH)2D and, by two independent assays, of 1α,25(OH)2D, and (b) indicate that serum values of the two dihydroxy metabolites of vitamin D in anephric subjects vary with the serum concentration of the precursor 25-OHD.