24-25-dihydroxyvitamin-d-3 and Nephrotic-Syndrome

Vitamin D metabolites were measured in sera of normal, vitamin D deficient and nonazotemic nephrotic rats. The concentrations of all metabolites were reduced in nephrotic and vitamin D deficient animals although 1,25-dihydroxyvitamin D values remained relatively normal in the nephrotic group. Twenty-four hours after the intravenous injection of tritiated 25-hydroxycholecalciferol, approximately 34% of the injected radioactivity appeared in the urine of the nephrotic animals compared with 0.4% in the controls. In extracts from nephrotic sera subjected to high performance liquid chromatography, the percentage of radioactive counts comigrating with 1,25-dihydroxycholecalciferol and 24,25-dihydroxycholecalciferol was significantly increased. The various metabolites were present in urine in approximately the same ratios as in serum. Dynamic histomorphometry of tibial metaphyses showed no abnormality. Urinary losses of vitamin D metabolites constitute the major cause for low serum values in nephrotic rats. The apparent synthetic rates are not impaired.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Bone and Bones; Calcifediol; Calcitriol; Calcium; Carrier Proteins; Dihydroxycholecalciferols; Male; Nephrotic Syndrome; Rats; Rats, Inbred Strains; Vitamin D; Vitamin D Deficiency; Vitamin D-Binding Protein

Patients with nephrotic syndrome (NS) lose 25-hydroxyvitamin D3 (25OHD3) in the urine and have low blood levels of this metabolite. This abnormality may be responsible for the hypocalcemia, i.e. low ionized calcium. The mechanism of the hypocalcemia is not evident. It is possible that the low value of 25OHD results in low blood levels of other vitamin D metabolites, such as 1,25-dihydroxyvitamin D [1,25-(OH)2D] and 24,25-(OH)2D3; a deficiency of these compounds may cause defective intestinal absorption of calcium (alpha) and resistance to the calcemic action of parathyroid hormone (PTH), resulting in hypocalcemia. Studies were performed in 12 patients with NS and normal renal function to evaluate these questions. Blood levels of 25OHD, 1,25-(OH)2D, and 24,25-(OH)2D were all significantly (P < 0.01) lower in NS (4.0 +/- 0.8 ng/ml, 7.0 +/- 2.3 pg/ml, 1.8 +/- 0.2 ng/ml, respectively) compared to normal subjects (37.0 +/- 1.5 ng/ml, 37.0 +/- 1.2 pg/ml, and 3.4 +/- 0.2 ng/ml). Both alpha (0.21 +/- 0.2 vs. 0.27 +/- 0.1; P < 0.05) and the calcemic response to PTH (0.50 +/- 0.1 vs. 1.35 +/- 0.16 mg/dl; P < 0.01) in NS subjects were significantly lower than normal. The data indicate that 1) a deficient state of all of these vitamin D metabolites exists in patients with NS and normal renal function, 2) this abnormality underlies the defect in alpha and the resistance to the calcemic response to PTH, and all participate in the genesis of the hypocalcemia, 3) secondary hyperparathyroidism develops, and 4) both vitamin D deficiency and elevated blood levels of PTH are responsible for the bone lesions in these patients.

Topics: 24,25-Dihydroxyvitamin D 3; Adolescent; Adult; Calcifediol; Calcitriol; Calcium; Dihydroxycholecalciferols; Female; Humans; Hydroxycholecalciferols; Male; Middle Aged; Nephrotic Syndrome; Parathyroid Hormone; Vitamin D

A specific competitive protein binding assay for 24,25-dihydroxyvitamin D by Sephadex LH-20 column chromatography, followed by high pressure liquid chromatography with normal rat kidney cytosol as the binding protein, was developed. The mean concentrations of serum 24,25-dihydroxyvitamin D of the cord, in newborn infants and in infants under 12 months of age were 0.90 +/- 0.40 (S.D.) ng/ml, 0.52 +/- 0.21 (S.D.) ng/ml and 1.20 +/- 0.38 (S.D.) ng/ml, respectively. These concentrations were significantly lower than those in children aged 1-15 years (1.96 +/- 0.83 (S.D.) ng/ml). The serum levels in the acute stage of the nephrotic syndrome were significantly reduced, and they increased in remission. These results show that patients wioth nephrotic syndrome have low levels of serum 24,25-dihydroxyvitamin D. This is probably due to its loss in the urine.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Child; Child, Preschool; Dihydroxycholecalciferols; Humans; Hydroxycholecalciferols; Infant; Infant, Newborn; Nephrotic Syndrome; Radioligand Assay; Rats

Serum concentrations of 25-hydroxyvitamin D (25OHD) and 24,25-dihydroxyvitamin D (24,25(OH)2D) in patients with various types of renal disease were measured by a competitive protein binding assay. There was a significant (P less than 0.001) inverse correlation between serum levels of either 25OHD or 24,25(OH)2D and the degree of proteinuria in patients with chronic glomerulonephritis or idiopathic nephrotic syndrome. The ratio of 24,25(OH)2D to 25OHD was relatively low in patients with creatinine clearances (CCr) less than 30 ml/min/1.48 m2, while the ratio was higher in those with clearances greater than 85 ml/min/1.48 m2. There was a linear correlation (r = 0.783, P less than 0.001) between the ratio and the CCr in patients whose CCR ranged from 30 to 85 ml/min/1.48 m2. The 24,25(OH)2D/25OHD ratio also appeared to be correlated significantly (P less than 0.001) with the PSP-test. The serum levels of 25OHD and 24,25(OH)2D were lowered in nephrotic patients during treatment with prednisolone. The serum levels of 24,25(OH)2D were increased by 1 alpha-hydroxyvitamin D3 treatment in patients with chronic renal failure.

Topics: 24,25-Dihydroxyvitamin D 3; 25-Hydroxyvitamin D 2; Adolescent; Adult; Child; Child, Preschool; Chromatography, Gel; Chromatography, High Pressure Liquid; Dihydroxycholecalciferols; Female; Glomerulonephritis; Humans; Hydroxycholecalciferols; Male; Methods; Middle Aged; Nephrotic Syndrome; Protein Binding