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

Phosphate retention plays a major role in the pathogenesis of hyperparathyroidism at all stages of renal insufficiency. Dietary phosphate restriction is mandatory only for adults and is not advised for children because of the recommended diet allowance. Dietary restriction is usually not sufficient, and phosphate binders are almost always necessary when the glomerular filtration rate falls below 40 mL/min. Because long-term administration of aluminum phosphate binders is associated with risk of aluminum intoxication despite the use of so-called "safe doses", alternative phosphate binders should be used. Magnesium hydroxide and carbonate can be used only for dialysis patients because a low dialysate magnesium concentration is necessary to prevent the hazards of hypermagnesemia. Therefore, the major alternative is the use of alkaline salts of calcium. The most recently proposed salt, acetate, has a higher phosphate-binding capacity than carbonate but exposes patients to the same incidence of hypercalcemia despite the use of half the dose of elemental calcium. These salts should be taken with meals in order to complex more dietary phosphate and decrease calcium absorption and therefore the risk of hypercalcemia. Oral calcium alone, without 1 alpha OH-vitamin D3 derivatives, can prevent hyperphosphatemia and hyperparathyroidism in most uremic patients before dialysis and in about half of the patients dialyzed with a dialysate calcium of 1.5 to 1.65 mmol/L. 1 alpha OH-vitamin D3 derivatives, which increase intestinal absorption of phosphate, should be used only when hyperphosphatemia has been prevented by oral calcium and diet and when plasma parathyroid hormone levels increase above three times the upper limit of normal. To decrease hypercalcemic risk, patients should be given 1 alpha OH-vitamin D3 derivatives, preferably at night, as an intermittent bolus (intravenous or oral). In dialysis patients, the dialysate concentration of calcium may have to be further decreased in order to prevent hypercalcemia when high doses of oral calcium are necessary to control hyperphosphatemia.
 ...
PMID:Management of hyperphosphatemia in patients with renal failure. 785 19

Ca2+ binds to a parathyroid cell Ca2+ receptor, which is G protein-coupled and activates inositol triphosphate production. Mutations in the Ca(2+)-sensing receptor gene cause familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism. Chronic hypocalcemia increases parathyroid hormone messenger RNA levels and parathyroid cell hyperplasia. Parathyroid cells in vitro are heterologous in their response to Ca2+. The concept of a higher Ca2+ set-point in secondary hyperparathyroidism is controversial. Calcitriol is more effective than the less hypercalcemia analogues in decreasing parathyroid hormone messenger RNA and immunoreactive parathyroid hormone levels, and its kinetics are well established. Phosphate and estrogens regulate the parathyroid independently of 1,25 dihydroxyvitamin D3 and Ca2+. The physiology of the effects of endothelin and insulin-like growth factors on the parathyroid need to be established. Important advances are being made in understanding the regulation of parathyroid hormone synthesis and secretion, which are relevant to both normal physiology and the pathogenesis and treatment of diseases such as the secondary hyperparathyroidism of renal failure and osteoporosis.
 ...
PMID:New aspects in the control of parathyroid hormone secretion. 807 41

Phosphate binders are necessary to control hyperphosphataemia in the majority of dialysis patients. Whilst aluminium salts are efficient phosphate binders, their use is associated with toxic side effects. Calcium salts are a widely used alternative, but hypercalcaemia is a common side effect, limiting their use and raising concern about metastatic calcification. Reduction of the dialysis fluid calcium concentration has been shown to reduce hypercalcaemia in haemodialysis patients, with an associated decrease in serum PTH. We analysed the effect of reduced calcium/magnesium (1.25/0.25 mmol/l), 40 mmol/l lactate, PD fluid (PD4) on 11 CAPD patients with uncontrollable hypercalcaemia (> 2.65 mmol/l) and hyperphosphataemia (> 1.80 mmol/l). Only 1 patient remained hypercalcaemic, while phosphate fell in 6 patients (2.23 +/- 0.16 on no binder, to 1.68 +/- 0.08 mmol/l at 6 months (p < 0.05), but was unchanged in 5 (2.10 +/- 0.15 to 2.48 +/- 0.14 mmol/l [p = NS]). Overall mean calcium x phosphate product changed little. However, in a subgroup it fell significantly (p < 0.05). Geometric mean iPTH rose, but not significantly. The subgroup of patients whose calcium x phosphate product fell, exhibited a much smaller rise in iPTH than the others (57.3-73.2 vs. 52.8-167.1 pg/ml). 1.25-Dihydroxyvitamin D3 was subnormal in all patients. Mean serum magnesium fell from 1.24 +/- 0.06 to 0.89 +/- 0.04 mmol/l (p < 0.001), whilst mean serum bicarbonate rose significantly (25.2 +/- 0.4 to 28.9 +/- 1.2 mmol/l; p < 0.01). Withdrawal of aluminium-containing phosphate binders resulted in mean serum aluminium falling significantly from 31.1 +/- 5.7 at start of PD4 to 15.4 +/- 2.7 mu g/l at 6 months (p < 0.05). In summary, in around 50% of CAPD patients with persistent hypercalcaemia and hyperphosphataemia, reduction in PD fluid calcium can produce significant improvement in phosphate, reduction of calcium x phosphate product, and enable avoidance of aluminium-containing phosphate binders. Patients whose calcium and phosphate control remains poor, still benefit from the reduction, or cessation, of oral aluminium intake.
 ...
PMID:Hypercalcaemia, hypermagnesaemia, hyperphosphataemia and hyperaluminaemia in CAPD: improvement in serum biochemistry by reduction in dialysate calcium and magnesium concentrations. 890 61

The purpose of the study was to evaluate the effectiveness of the oral pulse therapy with high doses of alphacalcidol (1 alpha(OH)D3) in secondary hyperparathyroidism. 16 hemodialysis patients with 4 to 9-fold iPTH serum elevation were given ones in week oral 1 alpha(OH)D3 in doses from 5.0 to 7.0 micrograms (0.1 microgram/b.m.) according to serum levels of calcium, phosphate, activity of alkaline phosphatase with its bone fraction. Serum iPTH levels were measured every 3rd month of the treatment. The dialysate calcium was reduced to 1.25 mmol/l. CaCO3 was used as a main phosphate binder in doses from 3.0 to 9.0 g/day. After first three months of treatment the serum iPTH levels decreased from 486.0 +/- 200 pg/ml to 218.0 +/- 117 pg/ml (p = 0.0001). Calcium levels increased from 2.39 +/- 0.2 mmol/l to 2.52 +/- 0.29 mmol/l (p > 0.05). Phosphate levels increased from 2.15 +/- 0.67 mmol/l to 2.17 +/- 0.62 mmol/l (p > 0.05). Alkaline phosphatase levels decreased from 35.2 +/- 17.3 IU/l to 31.1 +/- 7.78 IU/l (p > 0.05). Bone isoenzyme of alkaline phosphatase decreased from 19.2 +/- 13.4 IU/l to 15.5 +/- 7.51 IU/l (p > 0.05). Because of early serum hypercalcemia, doses of 1 alpha(OH)D3 had to be reduced in 2 patients. In 8 patients (50%) demonstrating decrease of serum iPTH levels (below 200 pg/ml) after first 3 months of treatment doses of 1 alpha(OH)D3 were reduced in the following months. We conclude that oral 1 alpha (OH)D3 pulse therapy is effective for parathyroid activity suppression in patients with severe hyperparathyroidism. To avoid dangerous hypercalcemia and adynamic bone disease serum iPTH and calcium levels should be strictly monitored.
 ...
PMID:[Evaluation of the treatment efficacy of secondary hyperparathyroidism with oral pulse doses of alphacalcidol]. 955 90

Phosphate binders that contain aluminum or calcium are frequently prescribed to treat hyperphosphatemia in patients with end-stage renal disease (ESRD), but an accumulation of aluminum can lead to encephalopathy, aluminum-related bone disease (ARBD) such as osteomalacia, anaemia, and resistance to erythropoietin, and calcium accumulation can lead to hypercalcaemia. High phosphate concentrations are reduced in vitro and in vivo by a phosphate adsorption pill, which is synthesized by hydrolyzing ferrous sulfate in the presence of saccharides, to form an iron (III)-saccharide complex that is acid resistant and binds phosphate greater than iron (III) hydroxide alone. Under in vitro conditions, containing 3.26 mg P/dL, the iron (III)-sucrose complex showed the highest phosphate adsorption capacity at pH 2 with artificial gastric juice, 58.9 mg P/g binder. For the 7 day in vivo study, 0% (Group 1), 1% (Group 2), 4% (Group 3), and 8% (Group 4) iron (III)-sucrose complex was admixed into the rodent chow by weight and fed to 15 male Wistar rats. The weight and volume of the feces and urine, and the calcium, iron, and phosphorus excretions in the feces and urine samples were monitored for any signs of irregularity. Total urine outflow was collected during a 24-h period to determine the amount of phosphate recovered, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. The fecal iron excretion was significantly effected by the amount of binder ingested throughout the study for Group 2 (p < 0.001), Group 3 (p < 0.01), and Group 4 (p < 0.001). The urinary calcium excretion (mg/rat/24-h) significantly increased by the 7th day for Group 2 (p < 0.05) and Group 4 (p < 0.01) in comparison to the control. Finally, after 7 days, there was a significant drop in the urinary phosphorus levels (mg P/rat/24-h) in a dose dependent manner for Group 2: from 7.82 +/- 1.46 to 1.98 +/- 0.10 mg P/rat/24-h (102 mg P/dL/24-h; p < 0.05); Group 3: from 6.70 +/- 1.14 to 0.16 +/- 0.09 mg P/rat/24-h (6.0 mg P/dL/24-h; p < 0.01); and Group 4: from 8.25 +/- 0.67 to 0.04 +/- 0.01 mg P/rat/24-h (0.9 mg P/dL/24-h; p < 0.01). The results show that this new adsorbent might provide an alternative to conventional aluminum and calcium containing phosphate-binding agents for combating hyperphosphataemia.
 ...
PMID:Oral phosphate binders: phosphate binding capacity of iron (III) hydroxide complexes containing saccharides and their effect on the urinary excretion of calcium and phosphate in rats. 1051 89

Abnormalities in calcium and phosphorus metabolism are common, and metabolic bone disease develops often in patients with chronic renal failure (CRF). Effective clinical management includes measures to control phosphorus retention and prevent hyperphosphataemia, to maintain serum calcium concentrations within the normal range and to prevent excess parathyroid hormone (PTH) secretion by the judicious use of vitamin D sterols. Certain of these interventions appear to increase the risk of soft tissue and vascular calcification in patients with end-stage renal disease (ESRD), changes that may contribute to the development of cardiovascular disease. Current therapeutic approaches are thus being re-evaluated in an effort to limit these risks. Despite the importance of controlling phosphorus retention and preventing hyperphosphataemia in patients with CRF, current management strategies often are inadequate, particularly in those ingesting diets containing adequate amounts of protein. Results from clinical trials using daily haemodialysis strongly suggest that thrice-weekly haemodialysis regimens are only marginally adequate for achieving weekly phosphorus balance in many patients with ESRD. The safety of large oral doses of calcium as a phosphate-binding agent in patients with ESRD has also been questioned because excess amounts of calcium that are absorbed from the gastrointestinal tract may lead to ongoing calcium retention in those with little or no residual renal function. Arterial calcification and cardiac valve calcification are two serious complications that adversely affect cardiovascular haemodynamics. The use of large, often supraphysiological, doses of calcitriol or other vitamin D sterols to treat secondary hyperparathyroidism may aggravate hypercalcaemia and hyperphosphataemia, further increasing the risk of soft tissue and vascular calcification. Phosphate-binding agents that do not contain calcium, new vitamin D analogues and calcimimetic compounds offer new therapeutic alternatives for managing renal osteodystrophy. The integration of these novel agents into existing treatment regimens may provide safer and more effective methods for controlling secondary hyperparathyroidism and renal bone disease, while limiting the risks of soft tissue and vascular calcification in patients with CRF.
 ...
PMID:Medical management of secondary hyperparathyroidism in chronic renal failure. 1277 Dec 90

Phosphate (Pi) retention is a common problem in patients with chronic kidney disease, particularly in those who have reached end-stage renal disease (ESRD). In addition to causing secondary hyperparathyroidism and renal osteodystrophy, recent evidence suggests that, in ESRD patients, high serum phosphorus concentration and increased calcium and phosphorous (Ca x P) product are associated with vascular and cardiac calcifications and increased mortality. Dietary phosphorus restriction and Pi removal by dialysis are not sufficient to restore Pi homeostasis. Reduction of intestinal Pi absorption with the use of Pi binders is currently the primary treatment for Pi retention in patients with ESRD. The use of large doses of calcium-containing Pi binders along with calcitriol administration may contribute to over-suppression of parathyroid hormone secretion and adynamic bone disease as well as to a high incidence of vascular calcifications. When used in patients with impaired renal function, aluminium salts were found to accumulate in bone and other tissues, resulting in osteomalacia and encephalopathy.Sevelamer, an aluminium- and calcium-free Pi binder can reduce serum phosphorus concentration and is associated with a significantly lower incidence of hypercalcaemia, while maintaining the ability to suppress parathyroid hormone production. An additional benefit of sevelamer is its ability to lower low density lipoprotein-cholesterol and total cholesterol levels. Sevelamer attenuates the progression of vascular calcifications in haemodialysis patients, which may lead to lower mortality. The use of sevelamer in non-dialysed patients might aggravate metabolic acidosis, common in these patients. Several other calcium-free Pi binders are in development. Lanthanum carbonate has shown significant promise in clinical trials in ESRD patients. Magnesium salts do not offer a significant advantage over currently available Pi binders. Their use is restricted to patients receiving dialysis since excess magnesium must be removed by dialysis. Iron-based compounds have shown variable efficacy in short-term clinical trials in small numbers of haemodialysis patients. Mixed metal hydroxyl carbonate compounds have shown efficacy in animals but have not been studied in humans. Major safety issues include absorption of the metal component with possible tissue accumulation and toxicity.
 ...
PMID:Safety of new phosphate binders for chronic renal failure. 1464 Jul 73

The appearance of soft tissue calcifications in patients with chronic renal failure has been recognised as one of the serious complications of uremia. An elevated serum calcium-phosphate product has almost invariably been detected, although the exact mechanisms of precipitation are still not fully understood. Among the factors responsible for triggering the precipitation process are: hyperphosphatemia, secondary hyperparathyroidism, hypercalcemia, treatment with vitamin D3, etc. Phosphate binders have been used to prevent, among other things, soft tissue calcifications, and parathyroidectomy has most frequently been applied as the therapy of choice, once precipitation of calcium salts has occurred. We present a case of soft tissue calcifications in the gluteal regions of a chronic haemodialysis female patient. The therapy we chose was a combination of biphosphonate and deferoxamine. The patient was treated for two months. The regression of the soft tissue calcifications was very significant, as registered both clinically and radiologically. The exact mechanism by which this reversal was achieved needs further investigation.
 ...
PMID:Successful treatment of soft tissue calcifications in uremia. 1698 88

Phosphate homeostasis is preserved during variations in phosphate intake by short-term intrinsic renal and intestinal adaptations in transport processes, and by more long-term hormonal mechanisms, which regulate the efficiency of phosphate transport in the kidney and intestine. Recently, several phosphaturic peptides such as fibroblast growth factor 23 (FGF-23), secreted frizzled-related protein-4 (sFRP-4), extracellular phosphoglycoprotein (MEPE) and fibroblast growth factor 7 (FGF-7) have been shown to play a pathogenic role in several hypophosphatemic disorders such as tumor-induced osteomalacia (TIO), autosomal dominant hypophosphatemic rickets (ADHR), X-linked hypophosphatemic rickets (XLH), the McCune-Albright syndrome (MAS) and fibrous dysplasia (FD). These proteins induce phosphaturia and hypophosphatemia in vivo, and inhibit sodium-dependent renal phosphate transport in cultured renal epithelial cells. Interestingly, despite the induction of hypophosphatemia by FGF-23 and sFRP-4 in vivo, serum 1, 25-dihydroxyvitamin D (1alpha,25(OH)(2)D) concentrations are decreased or remain inappropriately normal, suggesting an inhibitory effect of these proteins on 25-hydroxyvitamin D 1alpha-hydroxylase activity. In FGF-23 knockout mice, 25-hydroxyvitamin D 1alpha-hydroxylase expression is increased and elevated serum 1alpha,25(OH)(2)D levels cause significant hypercalcemia and hyperphosphatemia. MEPE, however, increases circulating 1alpha,25(OH)(2)D. Circulating or local concentrations of these peptides/proteins may regulate 25-hydroxyvitamin D 1alpha-hydroxylase activity in renal tissues under physiologic circumstances.
 ...
PMID:The phosphatonins and the regulation of phosphate transport and vitamin D metabolism. 1722 71

The aim of the study was to establish the frequency of tubular dysfunction in 59 patients with nephrolithiasis, of whom 52 had unilateral and 7 bilateral calculosis. Before the study urinary infection was cured in all patients. Renal function was normal in all subjects. Hypercalcaemia was present in 8 patients, and hypercalciuria in 17 subjects. Phosphate clearance (CPO4) was increased in 40 patients, and had the same number of patients, decreased tubular reabsorbtion of phosphate (TRP). In 31 patients increased CPO4 and decreased percent of TRP was present. Renal threshold phosphate concentration was decreased in 17 patients. High fraction excretion of sodium was observed in 37 patients, while urine sodium level was higher than normal only in 4 patients. Decreased ability of renal acidification of urine was found in 5 patients, and decreased renal concentration ability in 10 subjects. The most common finding in the observed patients was the phosphate excretion defect usually accompanied with defect of calcium excretion, and defect of urine acidification.
 ...
PMID:[Renal tubular function in patients with nephrolithiasis]. 1797 30


<< Previous 1 2 3 Next >>