scholarly journals Kidney disease and vitamin D levels: 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and VDR activation

2011 ◽  
Vol 1 (4) ◽  
pp. 136-141 ◽  
Author(s):  
Adriana S. Dusso
1987 ◽  
Vol 65 (8) ◽  
pp. 2111-2112 ◽  
Author(s):  
Ajai K. Srivastav ◽  
L. Rani ◽  
K. Swarup

Intraperitoneal injections of either vitamin D3 (4 IU/100 g body wt.), 25 hydroxyvitamin D3 (100 ng/100 g body wt.), or 1,25 dihydroxyvitamin D3 (100 ng/100 g body wt.) for 15 days induced hypercalcemia, hyperphosphatemia, and depletion of calcium deposits in the paravertebral lime sacs in an anuran, Rana tigrina.


1994 ◽  
Vol 86 (5) ◽  
pp. 627-632 ◽  
Author(s):  
A. J. Shaw ◽  
M. E. Hayes ◽  
M. Davies ◽  
B. D. Edwards ◽  
F. W. Ballardie ◽  
...  

1. Cyclosporin A, an immunosuppressive drug used to treat psoriasis, stimulates renal synthesis of 1,25-dihydroxyvitamin D in rats. 1,25-Dihydroxy vitamin D can also reduce the activity of psoriasis, and in the present study we have examined the possibility that cyclosporin A mediates some of its actions in psoriasis by renal or extra-renal production of 1,25-dihydroxyvitamin D. 2. Treatment of 12 psoriatic patients with cyclosporin A (5 mg day−1 kg−1) for 3 months significantly improved the psoriasis activity and severity index and reduced glomerular filtration rate, but serum 1,25-dihydroxyvitamin D levels were not changed. However, 1–3 months after stopping cyclosporin A treatment, an increase in the psoriasis activity and severity index score was accompanied by a small, but significant, increase in serum 1,25-dihydroxyvitamin D concentration. Plasma 1,25-dihydroxyvitamin D levels in rats gavaged with cyclosporin A (15 mg day−1 kg−1 for 2 weeks) were significantly increased compared with controls, but a lower dose of cyclosporin A (2.4 mg day−1 kg−1) had no effect. Renal 25-hydroxyvitamin D-24-hydroxylase activity in rat kidney homogenates was not different between control and cyclosporin A-treated rats. Renal 25-hydroxyvitamin D-1α-hydroxylase activity was not detectable in these homogenates. Extra-renal production of 1,25-dihydroxyvitamin D by activated macrophages isolated from the synovial fluid of patients with inflammatory arthritis was reduced after incubation with cyclosporin A (0.1–10 μmol/l) for 30 h or 5 days. 3. It is unlikely that alteration of circulating 1,25-dihydroxyvitamin D concentration is one of the modes of action of cyclosporin A in psoriasis. Since cyclosporin A inhibits 1,25-dihydroxyvitamin D production by activated synovial fluid macrophages, it is unlikely that cyclosporin A mediates some of its therapeutic actions by local synthesis of 1,25-dihydroxyvitamin D within the psoriatic lesion.


1989 ◽  
Vol 17 (3) ◽  
pp. 226-242 ◽  
Author(s):  
E. Harju ◽  
R. Punnonen ◽  
R. Tuimala ◽  
J. Salmi ◽  
I. Paronen

The effects on general and bone metabolism of femoral neck fracture patients of 0.25 μg α-calcoid given orally twice daily ( n=9) and 25 μg calcitonin given subcutaneously 30 times ( n=10) in 10 weeks were studied against a control ( n=ll). Bone histology and histomorphometry showed non-age related osteoporosis in 30% and osteomalacia in 22% of the patients studied. Impaired serum vitamin D status was found in 47 – 88% of patients, secondary hyperparathyroidism and increased serum parathyroid hormone in 59% and decreased serum calcitonin levels in 69%. On histology, normal findings and non-age related osteoporosis on histology were associated with low serum levels of 25-hydroxyvitamin D3,1,25- and 24,25-dihydroxy vitamin D3. Very high serum levels of 1,25-dihydroxyvitamin D3 and low levels of 25-hydroxyvitamin D3 occurred in fracture patients with osteomalacia. Calcitonin improved calcium balance, reduced osteoporosis and increased the serum 1,25- and 24,25-dihydroxyvitamin D3 levels but had no effect on osteomalacia. Vitamin D reduced osteomalacia, slightly increased the serum 1,25-dihydroxyvitamin D3 concentration and decreased serum levels of parathyroid hormone. Both treatments gave a similar slight decrease in serum calcitonin concentrations. A mechanism of action for the treatments is suggested.


PEDIATRICS ◽  
1987 ◽  
Vol 80 (1) ◽  
pp. 97-101
Author(s):  
E. Takeda ◽  
Y. Kuroda ◽  
T. Saijo ◽  
E. Naito ◽  
H. Kobashi ◽  
...  

Three patients with clinically different severities of vitamin D-dependent rickets, type II, with alopecia, which is 1,25-dihydroxyvitamin D-receptor-defect rickets and is particularly resistant to treatment with calciferol analogues, were treated with large doses of lα-hydroxyvitamin D3 (1α-(OH)D3) and 2 g of calcium lactate. Except for the alopecia, all of the abnormalities of patients 1 and 2 were reversed by treatment with 3 µg/kg/d of 1α-(OH)D3, and those of patient 3, who had the severest manifestations, were reversed by treatment with 6 µg/kg/d. The serum 24,25-dihydroxyvitamin D concentrations of the three patients were low before treatment and those of patients 1 and 2 increased during treatment. These findings suggest that in patients 1 and 2, 25-hydroxyvitamin D-24-hydroxylase was stimulated via a 1,25-dihydroxyvitamin D-receptor-mediated system by treatment with 1α-(OH)D3.


1981 ◽  
Vol 27 (10) ◽  
pp. 1757-1760 ◽  
Author(s):  
M J Jongen ◽  
W J van der Vijgh ◽  
H J Willems ◽  
J C Netelenbos ◽  
P Lips

Abstract We describe a simultaneous assay for the principal vitamin D metabolites: 25-hydroxyvitamin D, 24-25-dihydroxyvitamin D, and 1,25-dihydroxyvitamin D. Special attention has been paid to simplification of the extensive extraction and purification procedures used in previously described simultaneous assays. All three metabolites were isolated with a single extraction step, followed by only one gradient liquid-chromatographic procedure. For final quantitation we used competitive protein binding assays, involving readily available binding proteins and commercially purchased tritiated vitamin D metabolites. Concentrations in the plasma of healthy subjects (mean age, 27 years), sampled during December were 51 (SD 17) nmol/L, 4.1 (SD 1.3) nmol/L, and 124 (SD 26) pmol/L for 25-hydroxyvitamin D, 24,25-dihydroxyvitamin D and 1,25-dihydroxyvitamin D, respectively. Intra- and interassay CVs for the three metabolites were 4.4 and 3.9%, 6.7 and 8.0%, and 7.0 and 4.8%, respectively.


1989 ◽  
Vol 76 (1) ◽  
pp. 81-86 ◽  
Author(s):  
B. C. Lalor ◽  
E. B. Mawer ◽  
M. Davies ◽  
G. A. Lumb ◽  
L. Hunt ◽  
...  

1. The serum concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D were measured in 44 patients with primary hyperparathyroidism. 2. In 14 patients the serum concentration of 1,25-dihydroxyvitamin D was greater than normal (142–337 pmol/l). One patient had a subnormal concentration of 1,25-dihydroxyvitamin D (36 pmol/l) but no other evidence of vitamin D deficiency. 3. The possible biological determinants of the serum concentration of 1,25-dihydroxyvitamin D were sought by multivariate analysis of relevant variables. The serum concentration of 1,25-dihydroxyvitamin D was found to be significantly and positively correlated with the serum concentrations of 25-hydroxyvitamin D (P < 0.001) and parathyroid hormone (P < 0.003), and with the glomerular filtration rate (P < 0.03), and negatively correlated with the serum concentrations of calcium (P < 0.02) and phosphate (P = 0.055) (multiple R = 0.638,P < 0.002). 4. In primary hyperparathyroidism the major determinant of serum 1,25-dihydroxyvitamin D is the availability of precursor 25-hydroxyvitamin D. 5. The finding that serum 1,25-dihydroxyvitamin D is commonly normal in patients with primary hyperparathyroidism despite an adequate state of vitamin D nutrition, can be explained in terms of the constraining influences of hypercalcaemia and variable degrees of renal dysfunction on the biosynthesis of 1,25-dihydroxyvitamin D.


Author(s):  
MARINA GERGES

Interest in vitamin D has dramatically increased over the past several decades. From the beginning, vitamin D was incorrectly named a vitamin when later it was discovered to be a member of the steroid hormone family. Over time, the vitamin D receptor was discovered along with its major circulating form, 25-hydroxyvitamin D, and its the hormonal ligand, 1,25-dihydroxyvitamin D. Classically, vitamin D was known to be important for enhancing intestinal absorption of calcium; however, interest grew in vitamin D when it was determined that vitamin D may be utilized by other tissues of the body. Vitamin D3 is made in the skin from 7-dehydrocholesterol under the influence of UV light. Vitamin D2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25- dihydroxyvitamin D (1,25(OH)2D). CYP2R1 is the most important 25-hydroxylase; CYP27B1 is the key 1-hydroxylase. Both 25OHD and 1,25(OH)2D are catabolized by CYP24A1. 1,25(OH)2D is the ligand for the vitamin D receptor (VDR), a transcription factor, binding to sites in the DNA called vitamin D response elements (VDREs). There are thousands of these binding sites regulating hundreds of genes in a cell-specific fashion. VDR-regulated transcription is dependent on modulators, the profile of which is also cell-specific. Analogs of 1,25(OH)2D are being developed to target specific diseases with minimal side effects.(Bikle , 2014)


2000 ◽  
pp. 673-679 ◽  
Author(s):  
R Theiler ◽  
HB Stahelin ◽  
M Kranzlin ◽  
G Somorjai ◽  
L Singer-Lindpaintner ◽  
...  

OBJECTIVE: To investigate influences of physical mobility and season on 25-hydroxyvitamin D-intact parathyroid hormone (iPTH) interaction in the elderly. DESIGN: We examined 188 frail institutionalized elderly at the expected nadir of their serum vitamin D concentrations (winter). This group was compared with 309 healthy ambulatory elderly at the expected time of maximum vitamin D repletion (summer), to accentuate the influences of season and physical activity. METHODS: Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, iPTH and urinary deoxypyridinoline (DPD) were measured. RESULTS: Vitamin D metabolites were significantly lower in the institutionalized elderly (P<0.0001), with an 82.5% prevalence of vitamin D deficiency (25-hydroxyvitamin D <12ng/ml) in institutionalized elderly in wintertime and 15.5% in ambulatory elderly in summertime. Overall, median iPTH did not differ between groups. However, median iPTH secretion in the presence of low vitamin D serum concentrations (5-30ng/ml) was greater in ambulatory elderly. This could be explained by lower mobility status being correlated with greater serum calcium concentrations (r=0.24, P=0.02 in women; r=0.35, P=0. 001 in men) and greater urinary excretion of DPD (r=0.41, P=0.0001 in women; r=0.42, P=0.0002 in men), independent of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and iPTH. CONCLUSIONS: These data support the hypothesis that immobility, even in the presence of vitamin D deficiency, acts as an overriding influence on bone metabolism by promoting bone resorption (measured as urinary DPD) and increasing serum calcium independent of iPTH. Therefore mobility status may substantially affect 25-hydroxyvitamin D threshold values and the degree to which patients benefit from vitamin supplementation.


1980 ◽  
Vol 26 (3) ◽  
pp. 444-450 ◽  
Author(s):  
R S Mason ◽  
D Lissner ◽  
H S Grunstein ◽  
S Posen

Abstract We describe a simplified assay for 24,25-and 1.25-dihydroxyvitamin D in human serum. It involves two preparative steps, and normal chick intestine is used in preparing cytosol-binding protein. Our results for 24,25-dihydroxyvitamin D include a reference interval of 2.9—16 nmol/L (1.2—6.7 microgram/L), a mean of 6.7 nmol/L (2.8 microgram/L), an intra-assay CV of 11%, and an interassay CV of 22%. For 1,25-dihydroxyvitamin D, these data were 29—168 pmol/L (12—70 ng/L), 86 pmol/L (36 ng/L), 12%, and 22%, respectively. In hypoparathyroid patients with vitamin D intoxication, mean concentrations of 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum were significantly above normal; the 1,25-dihydroxyvitamin D concentrations were significantly below normal. Patients with malabsorption and/or post-gastrectomy states had significantly subnormal values for both 25-hydroxyvitamin D and 24,25-dihydroxyvitamin D in serum, and there was a significantly negative correlation between each of these biochemical values and the severity of osteomalacia. We also discuss cost effectiveness of assaying vitamin D metabolites in human serum.


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