Impaired 24,25-Dihydroxyvitamin D Production in Anephric Human and Pig

Horst, Ronald L.; Littledike, E. Travis; Gray, Richard W.; Napoli, Joseph L.

doi:10.1172/jci110023

Cited by 76 publications

(29 citation statements)

References 14 publications

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“…First, our suggestion that lower quantities of 1a,25(OH) 2 D 3 and 24,25(OH) 2 D 3 represent decreased production of these metabolites in CKD is based on the premise that circulating levels of these compounds (1) are primarily of renal origin and (2) are determined primarily by rates of synthesis, not degradation or deposition in extravascular sites. It remains possible that nonrenal systems may be involved in this response to vitamin D therapy (2), as suggested by prior studies showing that anephric pigs retain the ability to generate 24,25(OH) 2 D 3 in response to cholecalciferol (39). Second, the use of metabolic ratios to assess in vivo 1a-hydroxylase and 24-hydroxylase activity is a newer concept that needs further validation.…”

Section: Discussionmentioning

confidence: 99%

Decreased Conversion of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 Following Cholecalciferol Therapy in Patients with CKD

Stubbs

Zhang

Friedman

et al. 2014

Clinical Journal of the American Society of Nephrology

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concentrations were lower in the CKD group; moreover, the absolute increase in 24,25(OH) 2 D 3 after therapy was markedly smaller in patients with CKD (change, 2.8 ng/ml [2.3-3.5 ng/ml] for controls versus 1.2 ng/ml [0.6-1.9 ng/ml] for patients with CKD; P,0.001). Furthermore, higher baseline FGF23 concentrations were associated with smaller increments in 24,25(OH) 2 D 3 for individuals with CKD; this association was negated after adjustment for eGFR by multivariate analysis.Conclusions Patients with CKD exhibit an altered ability to increase serum 24,25(OH) 2 D 3 after cholecalciferol therapy, suggesting decreased 24-hydroxylase activity in CKD. The observed relationship between baseline FGF23 and increments in 24,25(OH) 2 D 3 further refutes the idea that FGF23 directly contributes to 25(OH)D insufficiency in CKD through stimulation of 24-hydroxylase activity.

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Section: Discussionmentioning

confidence: 99%

Decreased Conversion of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3 Following Cholecalciferol Therapy in Patients with CKD

Stubbs

Zhang

Friedman

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…As regards 24,25(OH)2D, previous results in anephric subjects were conflicting. Values were reported as being either low (5,(18)(19)(20) or undetectable (20,21 (20). The failure to demonstrate detectable serum values in previous studies may be due to differences in methods, including sensitivity and accuracy of the binding assays and recovery after extraction and purification of serum samples (5).…”

Section: Discussionmentioning

confidence: 99%

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

Lambert¹,

Stern²,

Avioli³

et al. 1982

J. Clin. Invest.

130

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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 la,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 la,25(OH)2D correlated significantly with serum 25-OHD (r = 0.911, P < 0.01). Mean serum la,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 la,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 la,25(OH)2D, and (b) indicate that serum

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“…Inter-and intraassay coefficients of variation for this assay are 11 and 9%, respectively. The 24,25(OH)2D3 fraction from the two MPorosil columns was further chromatographed on a Zorbax-Sil column with a solvent system of isopropanol/dichloromethane (2:98) and a flow rate of 2 ml/min (19). 24,25-Dihydroxyvitamin D3 was quantitated using a competitive protein binding assay based on vitamin D deficient rat serum as previously described (16).…”

Section: Methodsmentioning

confidence: 99%