dihydrotachysterol and Kidney-Failure--Chronic

The available data with regard to the use of calciferol, dihydrotachysterol, and calcifediol in the management of renal insufficiency are reviewed. Very limited data are available with regard to calciferol therapy; with the advent of more active metabolites, the use of calciferol is not warranted. Dihydrotachysterol seems to be effective in the treatment of renal patients with osteitis fibrosa; its low cost makes therapy with this compound a reasonable alternative, although it should not be used in the treatment of patients with liver disease. Calcifediol seems to be effective in patients with osteitis fibrosa; however, limited data on histologic characteristics of bone are available. Detailed prospective studies are necessary to establish the therapeutic benefit of calcifediol.

Topics: Absorption; Calcifediol; Cholecalciferol; Dihydrotachysterol; Ergocalciferols; Humans; Kidney Failure, Chronic; Osteitis Fibrosa Cystica; Structure-Activity Relationship

Topics: Dihydrotachysterol; Dihydroxycholecalciferols; Drug Resistance; Humans; Kidney Failure, Chronic; Vitamin D; Vitamin D Deficiency

Topics: Amino Acids, Essential; Collagen Diseases; Dihydrotachysterol; Diuresis; Glomerulonephritis; Humans; Immunotherapy; Kidney Failure, Chronic; Phenacetin; Pyelonephritis; Vascular Diseases

Topics: Animals; Bone and Bones; Calcium; Calcium, Dietary; Chickens; Dihydrotachysterol; Dihydroxycholecalciferols; Feedback; Hydroxycholecalciferols; Hydroxylation; Hypoparathyroidism; Intestinal Absorption; Intestinal Mucosa; Kidney; Kidney Failure, Chronic; Liver; Parathyroid Hormone; Phosphorus; Rats; Strontium; Vitamin D

Topics: Adult; Age Factors; Calcinosis; Child, Preschool; Dihydrotachysterol; Humans; Hypercalcemia; Hyperparathyroidism, Secondary; Hyperplasia; Kidney Failure, Chronic; Kidney Transplantation; Parathyroid Glands; Parathyroid Hormone; Postoperative Complications; Preoperative Care; Pruritus; Transplantation, Homologous; Vitamin D

Topics: Bone and Bones; Bone Diseases; Calcium; Cholecalciferol; Dihydrotachysterol; Homeostasis; Intestinal Absorption; Kidney; Kidney Failure, Chronic; Uremia; Vitamin D

Because controlled trials in adults have shown accelerated deterioration of renal function in a small number of patients receiving calcitriol for renal osteodystrophy, we initiated a prospective, randomized, double-blind study of the use of calcitriol versus dihydrotachysterol in children with chronic renal insufficiency. We studied children aged 1 1/2 through 10 years, with a calculated glomerular filtration rate between 20 and 75 ml/min per 1.73 m2, and with elevated serum parathyroid hormone concentrations. Ninety-four patients completed a mean of 8.0 months of control observations and were randomly assigned to a treatment period; 82 completed the treatment period of at least 6 months while receiving a calcitriol dosage (mean +/- SD) of 17.1 +/- 5.9 ng/kg per day or a dihydrotachysterol dosage of 13.8 +/- 3.3 micrograms/kg per day. With treatment the height z scores for both calcitriol- and dihydrotachysterol-treated groups showed no differences between the two groups. In relation to cumulative dose, there was a significant decrease in glomerular filtration rate for both calcitriol and dihydrotachysterol; for calcitriol the rate of decline was significantly steeper (p = 0.0026). The treatment groups did not differ significantly with respect to the incidence of hypercalcemia (serum calcium concentration > 2.7 mmol/L (> 11 mg/dl)). We conclude that careful follow-up of renal function is mandatory during the use of either calcitriol or dihydrotachysterol because both agents were associated with significant declines in renal function. There was no significant difference between calcitriol and dihydrotachysterol in promoting linear growth or causing hypercalcemia in children with chronic renal insufficiency. Dihydrotachysterol, the less costly agent, can be used with equal efficacy.

Topics: Calcitriol; Child; Child, Preschool; Dihydrotachysterol; Double-Blind Method; Female; Glomerular Filtration Rate; Growth Disorders; Humans; Hypercalcemia; Infant; Kidney Failure, Chronic; Male; Prospective Studies; Treatment Outcome

Fifteen patients with dialysis osteomalacia were treated with 24,25-dihydroxyvitamin D3 in dosages up to 10 micrograms per day for two to 24 months. All had previously had no improvement during treatment with calcitriol but had been remarkably susceptible to hypercalcemia. When 24,25-dihydroxyvitamin D3 was given with either calcitriol or dihydrotachysterol, serum calcium levels were significantly lower than during treatment with calcitriol or dihydrotachysterol alone. Eight of nine patients who received combined therapy with 24,25-dihydroxyvitamin D3 and calcitriol for longer than two months had clinical improvement; six patients underwent repeated bone biopsy and showed evidence of improved bone mineralization. Patients who received 24,25-dihydroxyvitamin D3 alone did not improve clinically. Since 24,25-dihydroxyvitamin D3 appears to improve calcium homeostasis and bone mineralization in some patients with severe dialysis osteomalacia when administered with 1-hydroxylated vitamin D metabolites, further controlled studies are warranted.

Topics: 24,25-Dihydroxyvitamin D 3; Adult; Alkaline Phosphatase; Biopsy; Bone Resorption; Calcitriol; Calcium; Child, Preschool; Clinical Trials as Topic; Dihydrotachysterol; Dihydroxycholecalciferols; Drug Therapy, Combination; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Osteomalacia; Renal Dialysis; Time Factors

Topics: Alkaline Phosphatase; Bone and Bones; Dihydrotachysterol; Humans; Hydroxycholecalciferols; Hyperparathyroidism; Hypocalcemia; Kidney Failure, Chronic; Kidney Transplantation; Parathyroid Hormone; Renal Dialysis; Ultraviolet Therapy

Ensuring the integrity of a study such as the GFRD Study requires close cooperation among all groups involved with the study and the patient. Many factors may influence the outcome and validity of a multicenter, double-masked, randomized trial. Any dosage modifications that may need to be made rely totally on established communication between the centers, the DCC, and the Core Pharmacy. When the procedures outlined above are followed, masking is ensured and patient compliance can be measured.

Topics: Calcitriol; Child; Dihydrotachysterol; Double-Blind Method; Drug Administration Schedule; Growth Disorders; Humans; Kidney Failure, Chronic; Patient Compliance; Randomized Controlled Trials as Topic

Topics: Anthropometry; Calcitriol; Child; Data Interpretation, Statistical; Dihydrotachysterol; Growth Disorders; Humans; Hypercalcemia; Incidence; Kidney Failure, Chronic; Research Design; Sampling Studies; Statistics as Topic

Topics: Bone Diseases; Calcitriol; Dihydrotachysterol; Humans; Kidney Failure, Chronic; Renal Dialysis

Topics: Adult; Calcitriol; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

The effect of administration of 25 micrograms 24,25-dihydroxyvitamin D3 (24,25(OH)2D) combined with dihydrotachysterol (DHT2) on clinical, radiological, biochemical and bone histological parameters was assessed in ten children on chronic hemodialysis. Eight children had been treated with DHT2 prior to administration of 24,25(OH)2D. Addition of 24,25(OH)2D to the treatment resulted in a decrease in serum calcium values. Therefore higher doses of DHT2 were required to maintain serum-calcium levels between 2.4-2.8 mmol/l. Administration of 24,25(OH)2D did not modify the quality of bone, but histomorphometric investigation did show a significant reduction of the surface percentage of bone trabecula, in the iliac crest, covered with osteoclasts (oc%). Following the administration of 24,25(OH)2D an increase in bone mineralization was shown by X-rays of the wrists and measured by dual photonabsorptiometry. Addition of 24,25(OH)2D to the DHT2 treatment resulted in an increase in serum concentration of 24,25(OH)2D and a decrease in DHT2 levels. The present study suggests that administered 24,25(OH)2D interferes with DHT2 metabolism and increases DHT2 tolerance. Increased bone mineralization may be related to 24,25(OH)2D, a higher dose of DHT2 or both.

Topics: 24,25-Dihydroxyvitamin D 3; Adolescent; Bone and Bones; Calcium; Child; Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Dihydroxycholecalciferols; Drug Therapy, Combination; Female; Humans; Kidney Failure, Chronic; Male; Minerals; Renal Dialysis

16 patients with advanced renal failure and histologic evidence of renal osteodystrophy were treated with dihydrotachysterol (DHT) in a dose of 0.125-0.375 mg/day. All patients had creatinine clearances of less than 22 ml/min, but none were undergoing dialysis. The rate of deterioration in renal function was determined by serial measurements of the serum creatinine and by plotting the reciprocal of the serum creatinine against time. The duration of follow-up was 17.0 +/- 8.6 months. There was no significant deterioration in renal function in 12 patients. The remaining 4 patients showed acceleration in the rate of deterioration, but the relationship to DHT therapy was unclear.

Topics: Alkaline Phosphatase; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Creatinine; Dihydrotachysterol; Drug Evaluation; Humans; Kidney; Kidney Failure, Chronic; Metabolic Clearance Rate; Phosphates; Retrospective Studies; Time Factors

We treated 24 patients who had chronic renal insufficiency and renal osteodystrophy with either calcitriol (1,25-dihydroxyvitamin D3) or dihydrotachysterol. Renal function was evaluated before and during treatment to determine if these vitamin D analogues caused an accelerated rate of renal function deterioration. An accelerated rate of increase in the serum creatinine level was found in three of 12 patients in each treatment group after therapy was started, but the mean rate of increase during treatment did not differ significantly from the rate during the pretreatment control period in either group. The occurrence of hypercalcemia or an excessive serum calcium x phosphorus-product did not correlate with the rate of change in renal function during treatment with either drug. We concluded that children receiving calcitriol are not at greater risk for an accelerated rate of renal function deterioration than are children treated with dihydrotachysterol. Furthermore, neither vitamin D analogue could be directly implicated as a cause of an accelerated rate of renal function deterioration when episodes of hypercalcemia were transient and occurred infrequently.

Topics: Adolescent; Adult; Calcitriol; Calcium; Child; Child, Preschool; Chronic Kidney Disease-Mineral and Bone Disorder; Creatinine; Dihydrotachysterol; Humans; Hypercalcemia; Infant; Kidney; Kidney Failure, Chronic; Phosphorus; Retrospective Studies; Risk

Renal osteodystrophy in part due to secondary hyperparathyroidism, is one of the major unresolved problems affecting patients on chronic hemodialysis. In addition, evidence has shown that parathyroid hormone (PTH) is toxic to other organ systems besides bone. The results of a prospective study on the effect of propranolol in reducing PTH levels in chronic renal failure patients on hemodialysis are reported. Propranolol administration reduced PTH levels by over 50-75%. The levels of calcium, phosphorus, alkaline phosphatase and hematocrit were variable, but patients with severe derangements in these measurements also seemed to benefit from propranolol. It should now be determined by larger and longer studies whether these biochemical improvements can be translated into clinical benefits.

Topics: Alkaline Phosphatase; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Female; Humans; Hyperparathyroidism, Secondary; Kidney Failure, Chronic; Male; Parathyroid Hormone; Propranolol; Renal Dialysis

To explore the assumption on the functional inadequacy of renal alternative vitamin D synthesis during chronic renal failure, 50 subtotally-nephrectomized rats were treated with dihydrotachysterol, androgens, estrogens or androgens + estrogens. Fractional duodenal calcium absorption and calcium-binding protein content of intestinal mucosa were determined. Fractional duodenal calcium absorption was significantly decreased in uremic rats (6.61 +/- 1.64%). Dihydrotachysterol or androgen + estrogen administration lead to 3-fold increase in fractional duodenal calcium absorption, accompanied by the enhancement in calcium-binding protein content of mucosal layer. It is concluded that it is possible to stimulate intestinal calcium absorption during experimental chronic renal failure, probably via the rehabilitation of 1,25(OH)2D2 production.

Topics: Androgens; Animals; Calcium; Calcium-Binding Proteins; Dihydrotachysterol; Estrogens; Intestinal Absorption; Intestinal Mucosa; Kidney Failure, Chronic; Male; Rats; Rats, Inbred Strains

The morphologic and morphometric study of the femoral bones of rats with experimental renal insufficiency induced by the removal of the 5/6 of the renal tissue amount has been carried out. The administration of dihydrotachysterol to the animals reduced the incidence and severity of changes (nephrogenic osteodystrophy) in the examined parts of the rat skeleton.

Topics: Animals; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Kidney Failure, Chronic; Male; Rats

The effects of oral administration of calcium carbonate, aluminum hydroxide gel, dihydrotachysterol (DHT) and sodium bicarbonate on metabolic acidosis and plasma calcium and phosphate were studied in 7 patients with chronic renal failure. Single administration of calcium carbonate alleviated the acidosis and increased the urinary bicarbonate excretion. These effects were potentiated when aluminum hydroxide gel was administered in combination with calcium carbonate. The plasma calcium was increased by this combination therapy. The effects of these two agents on acidosis and plasma calcium were further enhanced by the additional administration of DHT. Urinary bicarbonate excretion was less during the treatment with aluminum hydroxide gel and calcium carbonate than with aluminum hydroxide gel and sodium bicarbonate, when the excretions were compared at the similar concentrations of plasma bicarbonate. Aluminum hydroxide gel and DHT are likely to enhance the effect of calcium carbonate, which works as an alkalinizing salt on acidosis, probably through increasing calcium absorption in the intestine. And the three agents suppress the leak of bicarbonate into the urine contributing to the improvement of acidosis.

Topics: Acidosis; Administration, Oral; Adolescent; Adult; Aluminum Hydroxide; Calcium; Calcium Carbonate; Dihydrotachysterol; Drug Therapy, Combination; Female; Humans; Kidney Failure, Chronic; Male; Phosphates

Topics: Dihydrotachysterol; Humans; Kidney Failure, Chronic; Vitamin D

Topics: Adolescent; Age Factors; Child; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Kidney Failure, Chronic

Topics: Adult; Alkaline Phosphatase; Aluminum Hydroxide; Bone and Bones; Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Female; Humans; Hydroxyproline; Kidney Failure, Chronic; Male; Osteomalacia; Parathyroid Hormone; Phosphates; Renal Dialysis

21 hypocalcemic patients on regular hemodialysis were treated for 2 months with 0.2 mg and for a further 2 months with 0.46 mg dihydrotachysterol daily. 8 normocalcemic patients served as a control group. Radiological and radiodensitometric investigations were undertaken in all patients at regular intervals. Slight signs of renal osteopathy with a predominant osteomalacic component could be established in the skeletal X-ray in 55% of all patients. Compared with a healthy collective, all dialysis patients showed a small but significant reduction of bone mineralisation radiodensitometrically before the beginning of treatment. During treatment with dihydrotachysterol, the patients showed a significant demineralisation of the skeleton. In four cases the characteristics of the osteopathy also increased in the skeletal radiography. During the same period of observation, none of the untreated patients showed any change of the bone mineralisation.

Topics: Absorptiometry, Photon; Adolescent; Adult; Alkaline Phosphatase; Bone and Bones; Bone Resorption; Calcinosis; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Creatinine; Dihydrotachysterol; Dose-Response Relationship, Drug; Drug Synergism; Female; Humans; Kidney Failure, Chronic; Long-Term Care; Male; Middle Aged; Parathyroid Hormone; Phosphates; Renal Dialysis

Topics: Calcium Phosphates; Chemical Phenomena; Chemistry; Cholecalciferol; Dihydrotachysterol; Drug Resistance; Female; Homeostasis; Humans; Kidney Failure, Chronic; Middle Aged; Vitamin D

Topics: Calcium; Calcium Radioisotopes; Cholecalciferol; Dihydrotachysterol; Feces; Female; Humans; Intestinal Absorption; Isomerism; Kidney Failure, Chronic; Magnetic Resonance Spectroscopy; Male; Renal Dialysis; Spectrophotometry, Infrared; Spectrophotometry, Ultraviolet

Topics: Animals; Bone Diseases; Calcium; Chemical Phenomena; Chemistry; Cholecalciferol; Dihydrotachysterol; Dihydroxycholecalciferols; Disease Models, Animal; Humans; Hydroxycholecalciferols; Isomerism; Kidney Failure, Chronic; Microradiography; Osteitis Fibrosa Cystica; Osteomalacia; Phosphates; Rats; Renal Dialysis; Uremia; Vitamin D

Topics: Administration, Oral; Adolescent; Adult; Aged; Aluminum Hydroxide; Calcium; Calcium, Dietary; Diet; Dihydrotachysterol; Feces; Glomerulonephritis; Humans; Kidney Failure, Chronic; Middle Aged; Nephrotic Syndrome; Phosphorus; Polycystic Kidney Diseases; Potassium; Uremia

Topics: Bone Diseases; Dihydrotachysterol; Humans; Kidney Failure, Chronic; Renal Dialysis; Uremia

Topics: Chronic Kidney Disease-Mineral and Bone Disorder; Dihydrotachysterol; Humans; Kidney Failure, Chronic; Renal Dialysis

Topics: Anti-Bacterial Agents; Blood Urea Nitrogen; Diet Therapy; Dihydrotachysterol; Female; Humans; Hypoparathyroidism; Kidney Calculi; Kidney Failure, Chronic; Middle Aged; Nephrocalcinosis; Time Factors

Topics: Adolescent; Adult; Calcium; Cholecalciferol; Dihydrotachysterol; Female; Follow-Up Studies; Humans; Hydroxyproline; Hypoparathyroidism; Kidney Failure, Chronic; Male; Middle Aged; Spectrum Analysis; Thyroidectomy; Vitamin D

Topics: Absorption; Adolescent; Adult; Autoanalysis; Biopsy; Bone Diseases; Calcium; Calcium Isotopes; Dihydrotachysterol; Humans; Hyperparathyroidism; Kidney Failure, Chronic; Middle Aged; Renal Dialysis; Time Factors; Vitamin D