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)

Orally administered calcium carbonate was evaluated as a phosphate binding agent in 15 children, ages 0.6 to 17.2 years, receiving maintenance dialysis. Changes in plasma aluminum concentration were assessed after discontinuation of treatment with aluminum-containing gels. The mean daily dose of calcium carbonate was 5.1 +/- 2.5 gm (384 +/- 315 mg/kg/day), and correlated inversely with body weight (r = 0.72, P less than 0.01) and age (r = 0.71, P less than 0.01). Mean serum calcium, phosphorus, and bicarbonate values were unchanged throughout the study. Plasma aluminum concentration fell from 90 +/- 51 to 34 +/- 22 micrograms/L (P less than 0.005). Dietary phosphorus intakes were 44 +/- 21 and 42 +/- 19 mg/kg/day during the control period and at the end of the study, respectively. Transitory hypercalcemia was the only side effect in 92% of the patients. In none of the patients did uncontrolled hyperphosphatemia, metabolic alkalosis, diarrhea, or symptoms or signs of hypercalcemia develop. Our data indicate that calcium carbonate is an effective phosphate binding agent in children receiving dialysis, and should be used in lieu of aluminum-containing gels in young children with renal failure.
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PMID:Effects of oral calcium carbonate on control of serum phosphorus and changes in plasma aluminum levels after discontinuation of aluminum-containing gels in children receiving dialysis. 370 25

The association of a critical reduction in renal mass with the subsequent destruction of remaining nephrons has been observed in several species. We studied this process in experimental rabbits after 1 2/3 nephrectomy to define the course and its pathogenesis in this species. Control rabbits underwent sham operative procedures. After renal ablation, rabbits became increasingly cachectic and developed polyuria and hypertension. Despite food intake similar to that of controls (grams per kilogram per day), experimental rabbits developed severe hypercalcemia by 5 to 8 weeks after renal ablation, a change that persisted until death. During the study 17 experimental animals died of uremia 9 to 27 weeks after surgery, and the remaining seven experimental and 25 sham-operated rabbits were sacrificed at 5 to 7 months. At death, 19/24 experimental rabbits had severe obstruction of their collecting systems by concretions of gravel (n = 3) or large calcium carbonate stones (n = 16). Renal biopsy at 4 weeks revealed focal interstitial round cell infiltration progressing by 12 weeks to diffuse tubulointerstitial inflammation and fibrosis. Histologic evidence of obstruction was also evident at this time and became extensive on all subsequent examinations. By contrast, the glomeruli remained well preserved without evidence of sclerosis. We speculate that chronic hypercalcemia and, perhaps more significantly, urinary obstruction may have altered intrarenal hemodynamics and prevented the development of progressive sclerosis observed in the rat remnant kidney model. The present study describes an experimental model of chronic hypercalcemia and spontaneous calcium carbonate nephrolithiasis.
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PMID:Subtotal nephrectomy in the rabbit: a model of chronic hypercalcemia, nephrolithiasis, and obstructive nephropathy. 371 20

A 64 year old woman had been on lithium carbonate for 12 years for manico-depressive psychosis. Mild asthenia leads to the diagnosis of primary hyperparathyroidism based on the findings of hypercalcemia up to 2.85 mmol/l inappropriate levels of parathormone and a non-suppressive rise of nephrogenic cyclic AMP. These symptoms were not relieved by removal of a chief cell adenoma of the left inferior parathyroid; surgical reexploration leads to the removal of an adenoma in a high, ectopic situation. Further venous samplings were collected during cervico mediastinal phlebography because of persistent hypercalcemia: parathormone levels were high in a thymic vein and a new cervicotomy revealed a fifth gland with an adenoma in the high mediastinum. After removal of the third adenoma, the patient became hypocalcemic. Lithium was not discontinued according to the patient's wishes. Eighteen months later she was well and normocalcemic on alfacalcidol therapy. Multiple adenomas of the parathyroids are rare (1.7 p. 100 to 5 p. 100) and the recurrence of an adenoma on a supernumerary gland is exceptional. Eighteen clinical cases of primary hyperparathyroidism under lithium therapy have been reported, but mild asymptomatic hypercalcemia with inappropriate increased parathormone levels seems to be more common. Duration of treatment is very variable: 1 day to 12 years, and serum calcium levels or up to 3.9 mmol have been observed. Ten patients underwent cervicotomy with removal of an adenoma 6 of them remaining under treatment, with 2 recurrences in our case. Five of the 8 non-operated patients remained on lithium therapy and showed mild hypercalcemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Multiple hypersecreting lesions of the parathyroid glands during treatment with lithium]. 371 17

We evaluated the effectiveness of calcium carbonate as a phosphate binder in 19 children with chronic renal failure; ten children were undergoing dialysis therapy (eight maintained by CAPD and two by hemodialysis). Twelve children had previously received aluminum hydroxide, while calcium carbonate was the primary phosphate binder used in seven children. Among all the children, the serum phosphorus level on no phosphate binder was 7.4 +/- 0.9 mg/dL, which decreased significantly (P less than .001) to 5.9 +/- 0.8 mg/dL during calcium carbonate therapy, while the serum calcium, bicarbonate, and creatinine were unchanged. The reduction in the serum phosphorus level occurred while dietary intake of calcium and phosphorus were unchanged, as demonstrated by three-day dietary records. The dose of calcium carbonate required to maintain the serum phosphorus in the normal range varied from 600 mg to 15 g/d (mean 7.4 g/d). Among the 12 children and four others who had received aluminum hydroxide, serum aluminum levels fell from 108.8 +/- 121.8 ng/mL to 36.1 +/- 29.1 ng/mL after aluminum hydroxide was stopped (P less than .05). Serum alkaline phosphatase and parathyroid hormone (PTH) levels during aluminum hydroxide therapy were similar to levels obtained during calcium carbonate therapy, while PTH levels fell in children treated initially with calcium carbonate. All the children have been observed for a mean of 12.0 months (range 4 months to 3 1/2 years). Hypercalcemia occurred in seven children, usually when vitamin D therapy was initiated or the dose changed. Hypercalcemia resolved with adjustment of the vitamin D or calcium carbonate dose in all but one patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium carbonate is an effective phosphorus binder in children with chronic renal failure. 382 69

The chronic renal and systemic acid-base effects of hyperparathyroidism in humans remain controversial and unresolved. The present studies evaluated the acid-base response of normal human subjects to a 13-day intravenous infusion of synthetic b(1-34) PTH sufficient to result in sustained hypercalcemia and hypophosphatemia. The acid-base response was biphasic: an initial transient renal acidosis developed on the first day of PTH infusion, followed by a prompt increase in net acid excretion and plasma [HCO3-] of sufficient magnitude to result in a steady state of mild metabolic alkalosis. The results indicate that: 1) sustained, continuous, experimentally produced hyperparathyroidism results in a steady state of mild metabolic alkalosis; 2) the alkalosis is both generated and maintained, at least in part, by renal mechanisms; and 3) reported renal acidosis in sustained clinical conditions of primary hyperparathyroidism is not attributable to either direct or indirect effects of PTH excess when present for a 2-week period, an interval sufficient to re-establish a new steady state of renal and systemic acid-base equilibrium.
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PMID:Acid-base homeostasis during chronic PTH excess in humans. 383 29

Reduced concentrating and diluting capacity of the kidney in acute and chronic hypercalcemia may partly be due to inhibition of transcellular sodium reabsorption (RNa) in the thick ascending limb of Henle's loop. To examine this hypothesis, local heat production and RNa were measured during normo- and hypercalcemia at comparable glomerular filtration rate (GFR) in volume expanded, anesthetized dogs. Changes in proximal RNa which might occur during CaCl2 infusion, were minimized by infusing acetazolamide (75 mg/kg body wt iv). When ultrafiltrable calcium was increased from 1.12 +/- 0.09 to 2.95 +/- 0.10 mmol/l, cortical heat production was unchanged, whereas outer medullary heat production fell by 32 +/- 4%. RNa was reduced by 32 +/- 6%. Bicarbonate reabsorption did not change but calcium reabsorption and potassium excretion increased significantly. The potassium content of cortex and outer medulla increased during hypercalcemia, whereas ouabain, an inhibitor of Na+, K+-ATPase reduces the potassium content. We conclude that hypercalcemia does not inhibit transcellular RNa in the diluting segment by a direct effect on the Na+, K+-ATPase or the mitochondria, but by interfering with the coupled NaCl transport across the luminal cell membrane.
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PMID:Inhibition of transcellular NaCl reabsorption in dog kidneys during hypercalcemia. 609 15

We examined the effect of parathyroid hormone (PTH), administrated for 24-48 h, on acid-base homeostasis in dogs. Parathyroid extract (PTH), 15 IU/kg/day, given subcutaneously, caused metabolic alkalosis (control vs. experimental; mean +/- SEM): plasma HCO3, 21.3 +/- 0.3 vs. 24.2 +/- 0.5 mEq/l (p less than 0.001); plasma H+, 37.7 +/- 1.1 vs. 35.7 +/- 1.4 nEq/l (p less than 0.05), and net acid excretion, 48.6 +/- 2.0 vs. 65.1 +/- 4.0 mmol/day (p less than 0.01). PTH administered by continuous intravenous infusion had similar effects (control vs. experimental): plasma HCO3, 21.4 +/- 0.4 vs. 23.6 +/- 0.7 mEq/l (p less than 0.001) and net acid excretion, 54.0 +/- 3.5 vs. 68.3 +/- 5.7 mmol/day (p less than 0.05). PTH, 8 IU/kg/day, had qualitatively similar but quantitatively less profound consequences. Bicarbonaturia was not observed in any group. The effects of PTH were similar in adrenalectomized dogs maintained on hormone replacement. Indomethacin (150 mg/day) prevented the renal effects of PTH so that no increase in net acid secretion occurred. However, metabolic alkalosis still developed: control vs. experimental plasma HCO3, 21.8 +/- 0.5 vs. 23.9 +/- 0.5 mEq/l (p less than 0.001). Dichloromethanediphosphonate blunted both the renal and nonrenal effects of PTH, such that hypercalcemia, metabolic alkalosis and increased net acid excretion were quantitatively less and delayed in onset. In summary, PTH administration for 24-48 h causes metabolic alkalosis in dogs, the result of renal and nonrenal mechanisms.
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PMID:Parathyroid-hormone-induced metabolic alkalosis in dogs. 622 Feb

We performed graded calcium infusions twice in six normal young men, once without medication and a second time after they had received therapeutic doses of lithium carbonate for 5 days. The serum lithium level was 0.73 +/- 0.08 meq/liter (mean +/- SE) at the beginning of the calcium infusion and reached 0.97 +/- 0.13 150 min after receiving a lithium dose (210 min after beginning the test). There was no significant difference in mean basal serum calcium, plasma PTH, or nephrogenous cAMP for the untreated and treated periods. There was also no significant difference in calcium suppressibility of PTH secretion, as reflected by changes in nephrogenous cAMP. Changes in plasma PTH in response to calcium infusion likewise did not differ for the two periods, with the exception of a slightly greater degree of suppression in the unmedicated state (77% vs. 57% on lithium: P less than 0.02, by paired t test) at the last time point of the calcium infusion. The data show that short term administration of therapeutic doses of lithium does not alter the set-point for calcium suppression of PTH secretion in man. Further studies of calcium suppressibility of PTH secretion in subjects receiving long term lithium therapy will be needed to evaluate the pathophysiology of lithium-induced hypercalcemia.
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PMID:The effect of short term lithium administration on suppressibility of parathyroid hormone secretion by calcium in vivo. 633 Jan 56

Hyperchloremic metabolic acidosis has been reported in clinical states of primary and secondary hyperparathyroidism (HPT). Acute administration of parathyroid hormone (PTH) decreases renal acidification in humans and dogs, but the renal and systemic acid-base effects of chronic HPT have not been extensively investigated. In chronically thyroparathyroidectomized (TPTX) dogs (group I), bPTH 1-5 U/kg twice daily resulted in sustained hypophosphatemia, hypercalcemia, and Cl- -resistant metabolic alkalosis that was of renal origin at least in part: delta [HCO3-]p + 4.1 +/- 0.8 meq/liter, P less than 0.01; delta [H+]p -4 +/- 1 neq/liter, P less than 0.001, days 10-12. The cumulative change (sigma delta) in net acid excretion (NAE) was +44 meq (day 9, P less than 0.05). Similarly, metabolic alkalosis of renal origin, at least in part, occurred when PTH was administered by chronic continuous intravenous infusion (group II). Since chronic administration of calcitriol in dogs results in metabolic alkalosis, plasma calcitriol concentration was measured and found not to be increased by chronic intravenous PTH administration. In intact dogs (group III), a continuous chronic intravenous infusion of the Ca2+ chelator, Na4EGTA (3.0 mmol/kg daily), substituted for an equimolar amount of prechelated EGTA (CaNa2EGTA), resulted in a model of hypocalcemic HPT and severe Cl- -resistant metabolic alkalosis: delta [HCO3-]p +9.1 +/- 1.9 meq/liter, P less than 0.05; delta [H+]p -5 +/- 1 neq/liter, P less than 0.01, days 6-8. NAE decreased significantly. Thus, whereas metabolic alkalosis induced by PTH administration could be accounted for by increased NAE (group I), EGTA-induced metabolic alkalosis was accounted for by an extrarenal mechanism of base input to extracellular fluid (group III). Neutralization of the extrarenal base input by chronic administration of HCl during the period of EGTA-induced HPT did not preclude the development of metabolic alkalosis (group V), suggesting that a renal component was present in EGTA-induced metabolic alkalosis as well as in models of primary HPT (groups I and II). During the steady state, in this group as in the groups administered PTH, the net endogenous load of acid to the systemic circulation requiring renal excretion was unchanged from control, as indicated by stable values of NAE not significantly different from control. Yet metabolic alkalosis persisted in the steady state.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Metabolic alkalosis in models of primary and secondary hyperparathyroid states. 641 11

Current evidence suggests that administration of 1,25(OH)2D3 to patients with chronic renal insufficiency results in suppression of secondary hyperparathyroidism only if hypercalcemia occurs. However, since the parathyroid glands possess specific receptors for 1,25(OH)2D3 and a calcium binding protein, there is considerable interest in a possible direct effect of 1,25(OH)2D3 on parathyroid hormone (PTH) secretion independent of changes in serum calcium. Recent findings indicate substantial degradation of 1,25(OH)2D3 in the intestine, therefore, it is possible that while oral administration of the vitamin D metabolite increases intestinal calcium absorption, the delivery of 1,25(OH)2D3 to peripheral target organs may be limited. We therefore compared the effects of orally or intravenously administered 1,25(OH)2D3 on the plasma levels of 1,25(OH)2D3 and the effects of these two modes of treatment on PTH secretion. Whereas oral administration of 1,25(OH)2D3 in doses adequate to maintain serum calcium at the upper limits of normal did not alter PTH levels, a marked suppression (70.1 +/- 3.2%) of PTH levels was seen in all 20 patients given intravenous 1,25(OH)2D3. Temporal studies suggested a 20.1 +/- 5.2% decrease in PTH without a significant change in serum calcium with intravenous 1,25(OH)2D3. In five patients the serum calcium was increased by the oral administration of calcium carbonate, the decrement in serum i-PTH was only 25 +/- 6.65% when compared with 73.5 +/- 5.08% (P less than 0.001) obtained by the administration of intravenous 1,25(OH)2D3. Thus, a similar serum calcium achieved by intravenous 1,25(OH)2D3 rather than calcium carbonate has a greater suppressive effect in the release of PTH. These studies indicate that 1,25(OH)2D3 administered intravenously rather than orally may result in a greater delivery of the vitamin D metabolite to peripheral target tissues other than the intestine and allow a greater expression of biological effects of 1,25(OH)2D3 in peripheral tissues. The use of intravenous 1,25(OH)2D3 thus provides a simple and extremely effective way to suppress secondary hyperparathyroidism in dialysis patients.
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PMID:Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxy-cholecalciferol in uremic patients. 654 16


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