Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiology, clinical presentation, prevention, and treatment of aluminum-related osteomalacia in renal-failure patients are reviewed. Aluminum-related osteomalacia can develop in patients exposed to high concentrations of aluminum either in dialysis solutions or through gastrointestinal aluminum absorption from aluminum-containing antacids used to treat hyperphosphatemia. Although the exact etiology of aluminum-related osteomalacia is unknown, aluminum is believed to inhibit bone mineralization by forming an inhibitory complex with citric acid at physiologic concentrations. The complex is deposited along bone mineralization fronts and in bone marrow. The major symptoms of aluminum-related osteomalacia include skeletal pain, fractures, and vertebral collapse. The disease is difficult to diagnose because patients may have normal or slightly elevated serum concentrations of calcium, phosphate, alkaline phosphatase, and parathyroid hormone. Direct measurement of bone aluminum content (using biopsy) is often needed to confirm diagnosis. The aluminum-chelating agent deferoxamine mesylate can be used to measure bone aluminum content indirectly. Aluminum intoxication can be managed either by preventing exposure to aluminum or by removing deposited aluminum from bone. New standards restrict aluminum content in dialysis solutions, and prevention now focuses on the use of aluminum-free phosphate binders for treatment of hyperphosphatemia. Calcium carbonate may be as effective as aluminum-containing antacids in controlling serum phosphate concentrations, but it should be used cautiously in patients who are hypercalcemic or at risk of developing metastatic calcification. Chelation therapy with deferoxamine has improved the symptoms and bone histology in a small number of patients. Clinical improvements have been seen in patients receiving intravenous deferoxamine 2-6 g per week for 20 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aluminum-related osteomalacia in renal-failure patients. 389 71

We encountered 11 patients with aluminum-associated bone disease (AABD), and treated them with deferoxamine (DFO). In 3 patients, a second bone biopsy was done during DFO treatment. Clinical features of AABD were compared with surgically proven secondary hyperparathyroidism (2 degrees HPT) with osteitis fibrosa on X-ray. Patients with AABD had disabling bone pain. This disease showed radiological signs ranging from normal, localized bone atrophy, to multiple fractures. It was characterized by increased soft tissue activity and localized abnormal uptake of 99mTc-MDP, detected by skeletal scintigrams. Patients with AABD had low levels of parathyroid hormone and alkaline phosphatase, but high aluminum (Al) levels compared to those with 2 degrees HPT. Serum Al increased after DFO administration, and the patients improved both clinically and histologically. 1-alpha-Hydroxyvitamin D3 (1-alpha-OH D3) was not effective for AABD. We concluded that the administration of antacids containing Al should be minimized in dialysis patients.
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PMID:Clinical features of aluminum-associated bone disease in long-term hemodialysis patients. 394 60

Hyperphosphatemia leads to the development of osteitis fibrosa in patients with chronic renal failure. In contrast, crippling osteomalacia may appear in uremic patients who are hypophosphatemic or aluminum intoxicated or who undergo total or subtotal parathyroidectomy. Thus, strict phosphorus control by use of aluminum-containing gels may ameliorate renal osteitis fibrosa, but may potentiate the development of osteomalacia. To evaluate this possibility, we compared the bone histologies of 10 chronic renal hemodialysis patients who consistently maintained predialysis phosphorus levels between 4-5 mg/dl (Strict-P) to those of 46 randomly selected dialysis patients (Random-P). We found that the Strict-P group had lower circulating immunoreactive PTH (P less than 0.02) and alkaline phosphatase (P less than 0.05) levels and, as expected, less evidence of hyperparathyroid bone disease. On the other hand, the Strict-P patients had osteomalacia, as evidenced by moderate osteoid accumulation and reduced capacity of bone to assume a fluorescent tetracycline label. Furthermore, all Strict-P patients had histological evidence of bone aluminum accumulation. We conclude that maintenance of normal serum P levels with aluminum-containing gels in hemodialysis patients prevents severe hyperparathyroid bone disease. Such treatment, however, is also attended by a moderate degree of aluminum-associated osteomalacia.
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PMID:Does strict phosphorus control precipitate renal osteomalacia? 394 54

Healthy mixed-bred dogs of both sexes had renal mass surgically reduced and were allowed 2 to 3 months for hypertrophy of the remnant kidney. They were then allotted into 3 groups with equal renal function and were fed 1 of 3 diets that differed in composition. Group 1 dogs (n = 6) were fed moist food that contained 50% protein, 2.34% Ca, and 1.64% P with a P-binding agent (basic aluminum carbonate gel) added. Group 2 dogs (n = 6) were fed a dry diet that contained 24.5% protein, 1.26% Ca, 1.21% P, and the same P-binding agent as used for group 1. Group 3 dogs (n = 7) were fed a moist diet that contained 16.1% protein, 0.38% Ca, and 0.3% P without a P-binding agent. Each group was fed its diet for 92 days and monitored for responses. Mortality associated with uremia occurred in 2 of 6 group 1 dogs, 0 of 6 group 2 dogs, and in 2 of 7 group 3 dogs. Among survivors, clinical signs were seen in the more azotemic dogs of group 1, but not in dogs of groups 2 and 3. The blood urea nitrogen, plasma P concentrations, and PCV values were most favorable in group 3 and least favorable in group 1. Marked differences between groups were not seen in plasma concentrations of protein, albumin, or Ca or in plasma alkaline phosphatase activity. Values for glomerular filtration rate did not change in any group during the experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of three diets on dogs with induced chronic renal failure. 399 28

Serum aluminum levels twice to three times those in controls were found in 30 of 36 workers in a factory in an atmosphere of alumina dust. Inorganic phosphate and total alkaline phosphatase levels were within normal range, with no clinical evidence of phosphate depletion syndrome. Serum intestinal alkaline phosphatase, acid phosphatase and adenosine triphosphate levels were significantly reduced in the group with high levels of aluminum. The finding that the mean prothrombin time was significantly prolonged is of particular interest with respect to beneficial antithrombogenic effect.
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PMID:Increased prothrombin time and metabolic changes with high serum aluminum levels following long-term exposure to Bayer-process alumina. 433 26

Ultracytochemical reactions for enzymatic markers were applied to study the effect of aluminum on some cell organelles of neurons in the Ammon cortex and spinal cord in rabbits. The results showed that aluminum caused an appearance of secondary lysosomes and an increase in the number of lysosomes. The latter finding was endorsed by statistical analysis of Ammon neurons using a two-sided t-test. Concomitantly, decrease of the intensity of the reaction for thiamine pyrophosphatase (TPPase) and nucleoside diphosphatase (NDPase) in the Golgi apparatus was found. The reaction for NDPase in the endoplasmic reticulum remained unchanged. Cytochemical reactions for alkaline phosphatase and Mg2+-activated adenosine triphosphatase in the plasmalemma of neurons were negative both in control and in aluminum-treated animals. Our data point to the activation of the system of intracellular digestion and suppression of the enzymatic activities (NDPase, TPPase) of the Golgi apparatus in CNS neurons of rabbits treated with aluminum.
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PMID:Cytochemical study on the effect of aluminum on neuronal Golgi apparatus and lysosomes. 614 49

High-aluminum dialysate exposure has been incriminated in the pathogenesis of vitamin D-resistant osteomalacia in patients undergoing long-term hemodialysis. Parathyroid-mediated osteitis fibrosa is rare in these patients. Thirteen patients undergoing longterm hemodialysis were transferred from a center (Unit A) where water used to prepare dialysate was high in aluminum (100 to 450 micrograms/liter) to a new center (Unit B) where dialysate was highly purified (aluminum concentration less than 10 micrograms/liter), and changes in calcium metabolism were studied over a 12-month period. After transfer of patients to Unit B, serum aluminum levels fell (p less than 0.01), whereas serum immunoreactive parathyroid hormone levels rose (p less than 0.01) over 10 months. Over this time, predialysis serum calcium levels did not alter significantly, whereas postdialysis serum calcium levels declined slightly (p less than 0.05). Serum phosphate levels did not alter. Serum alkaline phosphatase levels rose progressively in Unit B (p less than 0.001). Discontinuation of dialysate high in aluminum in patients undergoing long-term hemodialysis may facilitate a rise in parathyroid activity.
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PMID:Evidence of increased parathyroid activity on discontinuation of high-aluminum dialysate in patients undergoing hemodialysis. 643 9

Fifteen children undergoing continuous ambulatory peritoneal dialysis for 0.3 to 2.4 years were evaluated longitudinally for renal osteodystrophy. Immunoreactive parathyroid hormone, 25-OHD, total and ionized calcium, inorganic phosphate, and alkaline phosphatase levels were measured regularly. Skeletal radiographic studies were performed at the onset and conclusion of CAPD and at six-month intervals during therapy. All children received 1,25(OH)2D3 and aluminum hydroxide, and nine received supplemental calcium. Plasma 25-OHD concentrations were normal to elevated, and calcium increased steadily to high normal levels despite a trend to persistent hyperphosphatemia. The increased calcium levels suppressed parathyroid hormone overactivity in only one patient. At the onset of CAPD, nine patients had hyperparathyroid bone disease seen radiographically, three of whom also had rachitic lesions. At the end of CAPD, the hyperparathyroid lesions had improved in four patients, completely resolved in three, and deteriorated in two. Rachitic lesions had completely healed in two patients and improved in the third. However, among the six children without radiographically evident lesions at onset of CAPD, hyperparathyroid bone lesions developed in two and rachitic lesions in two others during CAPD. Although CAPD and appropriate therapy benefited most patients with renal osteodystrophy, the benefits were not uniform, and bone lesions deteriorated in some.
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PMID:Renal osteodystrophy in children undergoing continuous ambulatory peritoneal dialysis. 663 99

The influence of aluminium in dialysate on the effects of 1 alpha (OH)3 on hemodialyzed hypocalcemic patients with end-stage renal failure, was studied during a 24- to 42-month period. 51 hypocalcemic patients were divided into two groups; group 1 consisted of 28 patients who were dialyzed using dialysate prepared from reverse osmosed water; the 23 patients in group 2 used dialysate prepared from softened water. Aluminium concentration in the dialysate used for group 1 was less than the detectable limit (10 micrograms/l) in twelve times determinations, while that for group 2 was 23.1 +/- 9.2 micrograms/l (mean +/- SD, n = 14). By the administration of 1 alpha (OH)D3, the serum concentration of calcium was increased, and that of iPTH and alkaline phosphatase activity was decreased in both groups. Subperiosteal resorption of the finger bone, evaluated by Jensen's criteria, was significantly improved in group 1, while there was no improvement in group 2. Serum aluminium concentration in the patients of group 1 and group 2 were 46.6 +/- 6.3 and 84.7 +/- 13.9 micrograms/l, respectively, and the concentration of the latter was significantly higher than that of the former (p less than 0.01). It was also shown that there is a positive correlation between the extent of subperiosteal resorption and the concentration of aluminum in serum. Serum aluminium concentration and bone aluminium content were increased according to the duration of hemodialysis in the patients who were dialyzed using dialysate from softened water, while there was no correlation between the duration of hemodialysis and serum aluminium concentration for the patients of group 1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of aluminium on the effect of 1 alpha (OH)D3 on renal osteodystrophy. 663 56

We describe a sporadic, vitamin-D-resistant osteomalacic syndrome in 19 patients undergoing hemodialysis. The syndrome was found in less than 1.5% of patients from referring dialysis centers. All 19 patients had multiple fractures, severe myopathy, and many developed spontaneous hypercalcemia. Severe osteomalacia without evidence of secondary hyperparathyroidism distinguished this syndrome from other forms of renal osteodystrophy. Bone aluminum, measured in six patients, was greatly elevated. Therapy with calcitriol (1 alpha, 25-dihydroxycholecalciferol) lad to clinical improvement in seven patients with reduced pain and myopathy, decreased serum alkaline phosphatase, or both, but no improvement in bone histology. Patients who did not respond clinically to calcitriol developed marked hypercalcemia. The cause of this severe osteomalacia, which occurs despite normal or slightly elevated levels of serum calcium and phosphorus and fails to mineralize with calcitriol, is unclear.
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PMID:Vitamin-D-resistant osteomalacia in hemodialysis patients lacking secondary hyperparathyroidism. 689 20


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