24-25-dihydroxyvitamin-d-3 and Proteinuria

Plasma 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) concentration was shown to decrease during bed rest in several studies when baseline plasma 25-hydroxyvitamin D (25-OHD) concentration was sub-optimal. Dahl salt-sensitive female (S) rats, but not Dahl salt-resistant female (R) rats, demonstrated a 50% decrease in plasma 1,25-dihydroxycholecalciferol (1,25-(OH)(2)D(3)) concentration after 28 days of hind limb unloading (HU, disuse model) during low salt intake (0.3%). We tested the vitamin D endocrine system response of female S rats to hind limb unloading during high salt intake (2%, twice that of standard rat chow to mimic salt intake in the USA). Hind limb unloading resulted in lower plasma 25-OHD(3) concentrations in S-HU rats than in R-HU rats (P<0.05) and greater urinary loss of 25-OHD(3) by S-HU rats than by S rats (P<0.05). Plasma 1,25-(OH)(2)D(3) concentration of S-HU rats was half that of S rats, but was unchanged in R-HU rats. The association of low plasma 25-OHD concentration with decrease in plasma 1,25-(OH)(2)D concentration of hind limb unloaded rats and of bed rest participants (published studies) suggests that low vitamin D status might be a risk factor for decrease in plasma vitamin D hormone concentration during long-term immobilization or bed rest.

Topics: 24,25-Dihydroxyvitamin D 3; Adrenal Glands; Animals; Blood; Body Weight; Calcifediol; Calcitriol; Calcium; Female; Hindlimb Suspension; Organ Size; Parathyroid Hormone; Protein Binding; Proteinuria; Rats; Rats, Inbred Dahl; Sodium; Sodium Chloride, Dietary

To investigate the effects of lead and cadmium on the metabolic pathway of vitamin D3.. Blood and urinary cadmium and urinary total proteins were measured in 59 smelter workers occupationally exposed to lead and cadmium. In 19 of these workers, the plasma vitamin D3 metabolites, (25-hydroxycholecalciferol (25 OHD3), 24R, 25-dihydroxycholecalciferol (24R,25(OH)2D3) and 1 alpha,25-dihydroxycholecalciferol (1 alpha, 25(OH)2D3)) were measured together with blood lead. Vitamin D3 metabolites were measured by radioimmunoassay, (RIA), lead and cadmium by atomic absorption spectrophotometry, and total proteins with a test kit.. Ranges for plasma 25(OH)D3, 24R,25(OH)2D3 and 1 alpha,25(OH)2D3 were 1.0-51.9 ng/ml, 0.6-5.8 ng/ml, and 0.1-75.7 pg/ml, respectively. Ranges for blood lead were 1-3.7 mumol/l, (21-76 micrograms/dl), blood cadmium 6-145 nmol/l, and urinary cadmium 3-161 nmol/l. Total proteins in random urine samples were 2.1-32.6 mg/dl. Concentrations of lead and cadmium in blood showed no correlation (correlation coefficient -0.265) but there was a highly significant correlation between blood and urinary cadmium. Concentrations for 24R,25(OH)2D3 were depressed below the normal range as blood and urinary cadmium increased, irrespective of lead concentrations. High cadmium concentrations were associated with decreased plasma 1 alpha,25(OH)2D3 when lead concentrations were < 1.9 mumol/l and with above normal plasma 1 alpha,25(OH)2D3 when lead concentrations were > 1.9 mumol/l, Kruskal-Wallis analysis of variance (K-W ANOVA) chi 2 = 10.3, p = 0.006. Plasma 25(OH)D3 was negatively correlated with both urinary total proteins and urinary cadmium, but showed no correlation with plasma 24R,25(OH)2D3, 1 alpha,25(OH)2D3, blood lead, or blood cadmium.. Continuous long term exposure to cadmium may result in a state of equilibrium between blood and urinary cadmium. Cadmium concentrations in blood could be predicted from the cadmium concentration of the urine, (regression coefficient +0.35 SE 0.077). Exposure to cadmium alone decreased the concentrations of 1 alpha,25(OH)2D3 and 24R,25(OH)2D3, whereas exposure to both cadmium and lead increased the concentrations of 1 alpha,25(OH)2D3. It has been suggested that cadmium and lead interact with renal mitochondrial hydroxylases of the vitamin D3 endocrine complex. Perturbation of the vitamin D metabolic pathway by cadmium may result in health effect, such as osteoporosis or osteomalacia, risks which are possibly increased in the presence of lead.

Topics: 24,25-Dihydroxyvitamin D 3; Analysis of Variance; Cadmium; Calcifediol; Calcitriol; Cholecalciferol; Humans; Lead; Male; Metallurgy; Occupational Exposure; Proteinuria

In the present study calcium and vitamin D metabolism was studied in fifty patients with daily urinary protein excretion exceeding 3 g/24 hours. A positive correlation was seen between serum albumin and ionized calcium concentration (r = 0.51, p < 0.001). All patients with normal renal function had their intact PTH within normal range, though seven of these 16 had serum ionized calcium below the lower margin of the reference range. The mean serum albumin was significantly lower in the seven patients with low serum ionized calcium when compared with those with serum ionized calcium above the lower normal margin (19 g/l vs. 30 g/l, respectively, p < 0.001), but there was no difference in plasma intact PTH (3.7 +/- 1.3 pmol/l vs. 3.1 +/- 0.7 pmol/l, p = 0.21, ns.). Serum 25OHD3 correlated negatively with the degree of proteinuria (r = -0.50, p < 0.001) and positively with serum albumin (r = 0.66, p < 0.001). Serum 1,25(OH)2D3 was related to serum 25OHD3 (r = 0.39, p < 0.01), but its association with serum phosphate, PTH, the degree of proteinuria and renal function did not reach statistical significance. In conclusion, a significant correlation between serum ionized calcium and albumin was observed, and in hypoalbuminemia hypocalcemia did not induce PTH response of expected magnitude. In patients with marked hypoalbuminemia a low measured ionized calcium does not have the same clinical impact as it would have in normoalbuminemia and it has to be interpreted cautiously. Secondly, abnormal regulation of 1,25(OH)2D3, and in particular its dependency on 25OHD3, was observed in patients with heavy proteinuria.

Topics: 24,25-Dihydroxyvitamin D 3; Adolescent; Adult; Aged; Calcifediol; Calcitriol; Calcium; Creatinine; Female; Glomerular Filtration Rate; Homeostasis; Humans; Male; Middle Aged; Parathyroid Hormone; Proteinuria; Serum Albumin; Vitamin D