Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is a retrospective, clinical study evaluating the long-term outcome of subtotal parathyroidectomy (PTX) in 60 patients with chronic renal failure and severe secondary hyperparathyroidism. Patients were 41 +/- 2 years old (mean +/- SE) at the time of PTX, and followed for 69 +/- 6 months since the procedure. At the time of PTX, three patients had chronic renal failure, 53 had been on chronic hemodialysis, and four had received successful kidney transplants. In more than 80 per cent of patients, symptoms of hyperparathyroidism (bone pain and muscle weakness) resolved within weeks, and biochemical signs (hypercalcemia, and high plasma alkaline phosphatase and parathyroid hormone concentrations) returned to normal ranges within a year. Subperiosteal resorption, bone fractures, and soft tissue calcification frequently improved. Osteosclerosis (rugger-jersey spine), cystic bone changes, osteopenia, and vascular calcifications were, however, often unchanged or progressive. Five patients (8%) who had either persistent or recurrent hyperparathyroidism required additional surgical procedures, and two had subsequent improvement. Twelve patients who had aluminum associated bone disease diagnosed later continued to progress with a high incidence of bone fractures and severe osteopenia. Cystic bone changes, especially of the carpal bones, in association with carpal tunnel syndrome, probably representing amyloid bone disease, also did not respond to PTX. In conclusion, PTX is an effective surgical procedure to reverse complications of hyperparathyroidism in patients with end-stage renal disease, provided that other causes of osteodystrophy, such as aluminum or amyloid-associated bone diseases, are adequately excluded. We feel that subtotal PTX, leaving a small remnant in place, is the procedure of choice.
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PMID:Long term results of subtotal parathyroidectomy in patients with end-stage renal disease. 806 33

Adynamic (or aplastic) bone disease is a bone histologic pattern characterized by decreased bone formation rate, low cellularity, and normal or decreased osteoid thickness. It was first described in symptomatic patients undergoing dialysis who were overloaded with aluminum because of contaminated dialysate or chronic ingestion of aluminic phosphate binders; the evidence of the overload was extensive coloration (more than 25%) with aurin tricarboxylic acid, whereas the Perls stain coloration for iron was negative. We have, however, reported these histologic changes in asymptomatic patients with uremia who were never exposed to aluminum, in two patients before end-stage renal failure and in six patients undergoing dialysis. The main step in the prevention of adynamic bone disease is the absolute exclusion of aluminum exposition even by so-called "safe doses" of aluminum phosphate binders because in the long term they are never actually safe. Because idiopathic adynamic bone disease may nevertheless occur, parathyroid hormone suppressive treatment by oral calcium taken with meals as phosphate binders (+/- 1 alpha-hydroxyvitamin D3 derivatives) should be carefully monitored by measurements of plasma concentrations of not only calcium and phosphate but also of intact parathyroid hormone levels. In order to have normal bone formation rate levels, patient intact parathyroid hormone levels should be between one and three times the upper limit of the normal level. Although adynamic bone disease may not be a true bone disease when not due to aluminum, it is a risk factor for increased incidence of hypercalcemia and hyperphosphatemia and therefore for metastatic calcifications. Therefore, when hypercalcemia occurs with hyperphosphatemia and normal intact parathyroid hormone in patients treated with 1 alpha-hydroxyvitamin D3, it is proposed that the latter drug should be discontinued first, whereas oral calcium is increased to correct hyperphosphatemia, and calcium concentration is decreased in the dialysate to prevent hypercalcemia, even though plasma parathyroid hormone may increase up to three times the upper limit of the normal level. In patients previously exposed to aluminum, a deferoxamine test should be performed and a deferoxamine treatment started if the test is positive.
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PMID:Adynamic bone disease in patients with uremia. 807 43

We evaluated 259 dialysis patients using serum parathyroid hormone (PTH, IRMA; normal range 1 to 5.5 pM or 10 to 55 pg/ml), the deferoxamine infusion test and iliac crest bone biopsy to determine the various forms of renal osteodystrophy and their risk factors. Although half of the biopsied patients had low turnover osteodystrophy, evidence of aluminum toxicity was present in only 1/3 of them. Additional risk factors for this bone lesion included treatment with peritoneal dialysis, ingestion of calcium carbonate, diabetes mellitus and advanced age. The PTH levels in patients with the aplastic lesion were significantly lower than in patients with normal or high bone turnover lesions [7.7 +/- 6.1 vs. 36.9 +/- 3.2 pM (77 +/- 61 vs. 369 +/- 32 pg/ml), P < 0.0001]. Aside from hypercalcemia, these patients were relatively asymptomatic. In a second study, 10 patients on peritoneal dialysis with the aplastic lesion had their dialysate calcium lowered from 1.62 to 1.0 mM. This resulted in a significant increase in PTH levels, from [3.7 +/- 0.8 to 10.6 +/- 1.9 pM (37 +/- 8 to 106 +/- 19 pg/ml), P < 0.001] which persisted over the nine-month observation period. In conclusion, the aplastic lesion is the most common form of renal osteodystrophy, with aluminum intoxication implicated in only 1/3 of the cases. In the remainder, factors identified include therapy with peritoneal dialysis using supraphysiological dialysate calcium, oral CaCO3 intake and diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aplastic osteodystrophy without aluminum: the role of "suppressed" parathyroid function. 825 62

Calcium carbonate (CaCO3) is an effective phosphate (PO4) binder in uremics, and its use reduces aluminum (Al) intake. By maintaining high serum Ca2+, it decreases serum parathyroid hormone (PTH) levels. Hypercalcemia, however, often limits the dosage. In order to evaluate the effects of a low-Ca peritoneal dialysis solution (PDS) (1.25 mmol/L) on Ca metabolism, we studied the following in 12 continuous ambulatory peritoneal dialysis (CAPD) patients with hypercalcemia (6 with low PTH levels, low-turnover bone disease, group 1, and 6 with high PTH levels, high-turnover bone disease, group 2, documented by bone biopsies): serum Ca2+; serum PTH; bone morphology. The follow-up was 12 months. Results show that in both groups within the third month there was a decrease in serum Ca2+. In group 1 serum PTH increased, reaching the norm, and in group 2 it further increased exceeding the norm. Because in both groups serum Ca2+ was normal, it was possible to increase oral CaCO3 (10.5 +/- 2.5 g/day) to control PO4 levels and to stop Al gels. In group 2, in order to avoid the further rise of serum PTH, the low-Ca PDS was supplemented with 2 micrograms/day of 1,25(OH)2D3 (vitamin D3); this was followed by a reduction in serum PTH with no increase in Ca2+ and PO4. The use of low-Ca PDS may be useful in preventing hypercalcemia in CAPD patients treated with high oral doses of CaCO3 and in improving low-turnover bone disease, while low-Ca PDS supplemented with vitamin D3 improves high-turnover bone disease.
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PMID:Low- and high-turnover bone disease in continuous ambulatory peritoneal dialysis: effects of low-Ca2+ peritoneal dialysis solution. 839 44

A high incidence of adynamic bone disease not related to aluminum intoxication has been reported in continuous ambulatory peritoneal dialysis (CAPD). Since reduced parathyroid hormone (PTH) secretion may predispose to adynamic bone, we investigated whether parathyroid gland sensitivity may be depressed in CAPD in comparison with hemodialysis (HD). Thus we determined parathyroid function by the evaluation of the PTH-ionized calcium (ICa) relationship, which was obtained inducing hypocalcemia and hypercalcemia in 19 CAPD and 18 HD patients with biochemical and histological evidence of mild (MILD) or severe (OF) hyperparathyroidism, but negative stainable bone aluminum. Either CAPD or HD patients with OF showed a shift to the right of the sigmoidal PTH-ICa curve in comparison with patients with MILD, greater set point of calcium, and maximal PTH stimulation and inhibition. The PTH-ICa curve and the other parathyroid function parameters were not different in CAPD and HD patients within the same bone histological group. In conclusion, our data document that parathyroid gland activity is stimulated either in CAPD and HD patients with OF, but is not depressed in CAPD patients in comparison with HD patients.
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PMID:The sigmoidal parathyroid hormone-ionized calcium curve and the set point of calcium in hemodialysis and continuous ambulatory peritoneal dialysis. 839 45

A previous short-term study of 10 weeks in 8 patients had shown us that with half the dose of elemental calcium, calcium acetate (CaAc) could control predialysis plasma phosphate (PPO4) as well as calcium carbonate (CaCO3) but that the incidence of hypercalcemia was not decreased. To better appreciate the value of CaAc in comparison to CaCO3, CaAc was given to 28 patients on chronic hemodialysis (6 men, 22 women, age 61 +/- 14 years; dialyzate Ca:1.5 mmol/l) for 6 months to replace CaCO3 at half the dose of elemental calcium (1,235 +/- 521 versus 2,375 +/- 1,470 mg/day). Because of gastrointestinal intolerance, CaAc had to be discontinued in 5 patients after 1-5 months. Magnesium hydroxide [Mg(OH)2] given in 18 of them in association with CaCO3 was discontinued and reintroduced in 6 patients in order to keep PPO4 < 2 mmol/l. Mean dosage of Mg(OH)2 was 2.09 +/- 1.4 g/day with CaCO3 and 0.9 +/- 0.5 with CaAc. Predialysis plasma concentrations of calcium and phosphate were monitored weekly during the 3 months of the control period under CaCO3 and during the 6-month administration of CaAc. Plasma calcium (PCa) was comparable with the 2 treatments (2.47 +/- 0.11 vs. 2.5 +/- 0.10 mmol/l), but PPO4 was significantly lower with CaAc (1.82 +/- 0.26 vs. 1.73 +/- 0.23 mmol/l). Plasma alkaline phosphatase remained constant (122 +/- 66 vs. 122 +/- 70; normal < 170 UI/l) as well as plasma intact PTH (121 +/- 153 vs. 121 +/- 146; normal < 54 pg/ml) and plasma aluminum (0.34 +/- 0.23 vs. 0.32 +/- 0.20 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term (6 months) cross-over comparison of calcium acetate with calcium carbonate as phosphate binder. 844 61

Burn patients are at risk for bone disease due to aluminum (Al) exposure from use of antacids and albumin, partial immobilization, and increased production of endogenous glucocorticoids. Moreover, severely burned children are growth impaired up to 3 years after the burn. To determine the extent of bone disease, we studied nine men and three women, ages 18-41 years, with greater than 50% body surface area burn. Seven patients underwent iliac crest bone biopsy following double tetracycline labeling, one additional patient expired after a single label, and three others had postmortem specimens obtained for quantitative Al only. Serial serum and urine samples were obtained weekly until biopsy or death. All biopsied patients had reduced bone formation and osteoid area, surface, and width, with mineral apposition rate, osteoblast surface, and osteoclast number with normal eroded surfaces compared to age- and sex-matched normal ambulatory volunteers. Burn patients also had reduced bone formation, mineral apposition rate, osteoid area, and surface compared to age-matched volunteers at short-term bed rest. Serum levels of osteocalcin were low. Most patients had mild hypercalcemia but only a third had hypercalciuria. All patients had elevated Al in blood or urine; urine Al correlated inversely with serum osteocalcin. In 60% significant bone Al was detectable by stain or quantitation. Our data are compatible with burn patients having markedly reduced bone turnover. Al loading, partial immobilization, endogenous corticosteroids, and cytokine production may be among the etiologic factors.
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PMID:Bone disease in burn patients. 845 88

Calcium set point was measured in 12 patients on chronic hemodialysis. Dialysate calcium concentration was 1.65 mmol/l. Calcium carbonate (CaCO3) was used as the phosphate binder and oral 1-alpha hydroxycholecalciferol (alfacalcidol) was administered in a dose of 0.25-1.0 micrograms/day for 12 months. Comparing base line and post study values, there were no significant changes in ionized calcium (ICa++), intact immunoreactive parathyroid hormone (iPTH), plasma total calcium (TCa++), plasma phosphate (P), alkaline phosphatase (ALP), or aluminum (Al). However, the relative calcium set point significantly worsened (shifted to the right). Three patients developed hypercalcemia (25%) with a total calcium > 2.65 mmol/l. Total bone mineral content (BMC) fell suggesting demineralization. We conclude that this dose of oral alfacalcidol, CaCO3, and a dialysate calcium concentration of 1.65 mmol/l are not sufficient to halt the progression of secondary hyperparathyroidism in chronic hemodialysis patients. Measurement of calcium set point may be the best early measure of failure to prevent worsening of hyperparathyroidism.
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PMID:Calcium set point progressively worsens in hemodialysis patients despite conventional oral 1-alpha hydroxycholecalciferol supplementation. 849 Oct 50

The occurrence of aluminum-related bone disease should be completely prevented in uremic patients by restricting the use of aluminum-phosphate binders, which can be safely replaced by oral calcium carbonate. Factors other than aluminum may lead to adynamic bone disease in uremic patients. Radiolucent bone cysts are indicative of amyloid deposits, and their occurrence and progression may be influenced by the membranes used for hemodialysis. Bone disease may persist after successful renal transplantation, and the additional deleterious effect of immunosuppressive drugs should be emphasized. Primary hyperparathyroidism is the most frequent cause of hypercalcemia in the general population. Surgery should be undertaken when there is evidence of active disease, even in asymptomatic patients. The consequences of primary hyperparathyroidism on bone mass and bone fragility remain controversial, and histologic bone studies suggest that hyperparathyroidism leads to increased bone turnover without any deleterious effect on bone volume or trabecular architecture. The diagnostic value of a newly developed immunoassay for intact parathyroid hormone and parathyroid hormone-related protein is clearly demonstrated. New bisphosphonates are of major value for the management of hypercalcemia in malignancy.
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PMID:Renal osteodystrophy and hypercalcemia. 851 74

The use of 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] derivatives in a uremic patient is justified only in the treatment of hyperparathyroidism (i.e. when plasma intact parathyroid hormone - PTH - levels are above five or three times the upper limit of normal according to whether the patient is on continuous ambulatory peritoneal dialysis or on hemodialysis and between 0.5-1.5, 1-2 and 2-3 times the upper limit of normal for a creatinine clearance of, respectively, 30, between 30 and 10, or below 10 ml/min/1.73 m2). The following prerequisites have however to be satisfied: (1) a good vitamin D3 repletion should be secured by plasma 25(OH(D) levels of 20-30 ng/ml (if necessary by administration of native vitamin D or 25(OH)D3), and (2) phosphate retention (which is aggravated by the increased phosphate intestinal absorption induced by the 1 alpha (OH)D derivatives) and the consequent possible hyperphosphatemia should be prevented or corrected by the oral administration of alkaline salts of calcium given before the meals as phosphate binders without inducing hypercalcemia. These prerequisites explain the narrow therapeutical margin of 1 alpha (OH)D3 derivatives in uremic patients before dialysis (more so in the adult than in the child) and the possible broadening of this margin in the patients on dialysis by the use of low dialysate calcium concentrations (1.25-1.00 mmol/l) in order to prevent hypercalcemia by inducing a negative perdialytic calcium balance. Once hyperphosphatemia is prevented by oral calcium, 1 alpha (OH)D3 derivatives have the advantage to suppress the transcription of the prepro PTH gene by a mechanism independent of an increase in plasma calcium. Controlled randomized trials have not confirmed the claimed advantage in efficacy and safety of the parenteral versus the oral route nor of the intermittent versus the daily mode of their administration. The advantages of using the so called 'nonhypercalcemic hyperphosphatemic' vitamin D3 derivatives in combination with oral calcium over 1 alpha(OH)D3 derivatives in the treatment of uremic hyperparathyroidism are still waiting for clinical demonstration. Vitamin D derivatives have no place in the treatment of aluminic bone diseases which necessitate long term deferoxamine treatment and prevention of aluminum exposure by the dialysate and the phosphate binders. They are not indicated in the treatment of 'idiopathic' adynamic bone disease which is due to uremia per se combined with an excessive PTH suppression for the degree of renal failure. This low bone turnover pattern is associated with an increased risk of hypercalcemia and hyperphosphatemia and necessitates only a stimulation of PTH secretion by inducing a negative calcium balance with a lower dialysate calcium concentration or simply by discontinuing the oral calcium supplement in the uremic patient not yet dialyzed. In rare cases this pattern is due to a granulomatosis and is corrected by prednisone.
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PMID:1-alpha-Hydroxyvitamin D3 derivatives in the treatment of renal bone diseases: justification and optimal modalities of administration. 856 75


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