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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia and aluminum-based binders that result in total body aluminum accumulation over time. This investigation describes the use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis patients and compares it with a standard calcium-based phosphate binder. An open-label, randomized, crossover study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder washout period, stable hemodialysis patients were administered either sevelamer or calcium acetate, and the dosages were titrated upward to achieve improved phosphate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Eighty-four patients from eight centers participated in the study. There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-2.0 +/- 2.3 mg/dL) and calcium acetate (-2.1 +/- 1.9 mg/dL). Twenty-two percent of patients developed a serum calcium greater than 11.0 mg/dL while receiving calcium acetate, versus 5% of patients receiving sevelamer (P < 0.01). The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 24% mean decrease in serum low-density lipoprotein cholesterol levels. Sevelamer was effective in controlling hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium acetate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients, and its usage may be advantageous in the treatment of dialysis patients.
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PMID:A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients. 1087 27

Renagel is a novel, nonabsorbed, phosphate binding polymer free of aluminum and calcium. In hemodialysis patients, Renagel: lowers serum phosphorus levels; lowers intact parathyroid hormone levels; lowers calcium x phosphorous levels; lowers total serum and low density lipoprotein (LDL) cholesterol; and is safe and well tolerated (Bleyer et al., 1997; Chertow, Burke, Dillon, et al., 1998; Chertow, Burke, Goldberg, et al., 1997; Chertow, Burke, Lazarus, et al., 1997; Goldberg et al., 1998; Slatopolsky, Burke, Dillon, & The Renagel Study Group, 1999). Renagel treatment decreased total and low-density lipoprotein (LDL) cholesterol, but had no effect on high-density lipoprotein (HDL) cholesterol and triglycerides (Goldberg et al., 1998; Slatopolsky et al., 1999). This cholesterol-lowering effect of Renagel was most apparent in patients with LDL cholesterol of 100 mg/dl or greater at baseline; therefore, it may be beneficial for some patients. Longer-term studies in ESRD patients are required to determine the potential benefit of lipid lowering (Slatopolsky et al., 1999). The nephrology staff is responsible for delivering optimal patient care. This new drug allows for adequate control of phosphorous without incidence of hypercalcemia, or aluminum related problems.
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PMID:Renagel: a new and different phosphate binder. 1063 8

More than 60% of patients on chronic haemodialysis (HD) have a serum phosphate level above 5.5 mg/dl (1.75 mmol/l), which recently has been recommended as an appropriate target in patients with end-stage renal disease (ESRD). Preventing hyperphosphataemia and elevated Ca x P product not only ameliorates the progression of secondary hyperparathyroidism and bone disease, but also appears to reduce cardio-vascular morbidity and mortality from vascular calcifications. Dietary phosphate restriction and the administration of aluminium and calcium salts have been the principal means of phosphate control over the last decade. Unfortunately, the protean disturbances of toxic aluminium accumulation in the body virtually eliminated aluminium from clinical practice. Calcium-based therapy, although well tolerated, results in frequent hypercalcaemia when administered concurrently with vitamin D analogues, despite a decrease in the concentration of dialysate calcium. Sevelamer (Renagel((R))) has been a novel, non-absorbable calcium- and aluminium-free synthetic polymer. In initial studies, sevelamer reduced serum phosphate, Ca x P product and parathyroid hormone (PTH) in a manner comparable with calcium acetate therapy. However, the effect on PTH levels may prove to be inconsistent. It seems somewhat less effective in binding phosphate than aluminium, although no direct comparisons have been made. In a recent study, it attenuated the progression of vascular calcification in HD patients. It also binds bile acids, resulting in substantially lower low-density lipo-protein cholesterol levels. The major obstacle to its current use is a substantial increase in the cost associated with sevelamer therapy.
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PMID:Hyperphosphataemia and treatment with sevelamer in haemodialysis patients. 1281 70

Hyperphosphatemia and secondary hyperparathyroidism are common complications of ESRD (chronic kidney disease stage 5) that, when untreated, may result in increased morbidity and mortality. Hyperphosphatemia and hypercalcemia have been associated with increased coronary artery calcification. Achieving control of serum phosphorus without increasing serum calcium is an important goal for patients with ESRD. Although calcium-based phosphate binders effectively reduce serum phosphorus and parathyroid hormone concentrations, these agents can lead to hypercalcemia and have been associated with increased vascular calcification. The phosphorus binder sevelamer was developed to overcome the limitations associated with the usual management of hyperphosphatemia and secondary hyperparathyroidism (i.e., mineral salts). Sevelamer, a nonabsorbable hydrogel, is as efficacious as calcium-based phosphate binders for reducing serum phosphorus but does not cause hypercalcemia or other adverse metabolic effects. Sevelamer also exhibits beneficial effects on lipids, consistently and significantly decreasing LDL cholesterol and increasing HDL cholesterol in most studies. In a head-to-head randomized clinical trial, sevelamer and calcium-based binders achieved similarly excellent phosphorus control, but the use of calcium-based binders led to significantly higher serum calcium concentrations and an increased incidence of hypercalcemia and unintended suppression of parathyroid hormone. Treatment with calcium-based binders also led to the progression of coronary artery and aortic calcification, whereas sevelamer attenuated or arrested progression. Strategies that use oral calcium and vitamin D in patients with ESRD should be reexamined, and the potential advantages of sevelamer should be considered when selecting a primary agent to reduce serum phosphorus in hemodialysis patients.
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PMID:Slowing the progression of vascular calcification in hemodialysis. 1293 87

Hyperphosphatemia is one of the major complications of hemodialysis patients and plays a key role in the pathogenesis of cardiovascular calcification and secondary hyperparathyroidism. Dietary phosphate restriction and removal of phosphate by dialysis are insufficient to control hyperphosphatemia. Therefore, almost all patients undergoing hemodialysis should take oral phosphate binders. Sevelamer hydrochloride (sevelamer) is a novel phosphate-binding polymer that contains neither aluminum nor calcium, and it is not absorbed from the gastrointestinal tract. In rat models with progressive chronic renal insufficiency, in addition to lowering effects on serum levels of phosphorus, calcium x phosphorus product, and parathyroid hormone, dietary treatment of sevelamer can prevent parathyroid hyperplasia, vascular calcification, high turnover bone lesion, and renal functional deterioration. In clinical studies with hemodialysis patients, sevelamer lowers serum phosphorus and calcium x phosphorus product without any incidence of hypercalcemia. Switching calcium-containing phosphate binders to sevelamer can decrease the percentage of hypoparathyroidism and hyperparathyroidism by negative calcium balance and increased dosage of vitamin D, respectively. Sevelamer also decreases serum low-density lipoprotein cholesterol levels by its bile acid-binding capacity. A long-term clinical study has demonstrated that the progression of coronary and aortic calcification in hemodialysis patients is attenuated by sevelamer. Thus, sevelamer offers the promise of impacting cardiac calcification and thereby reducing morbidity and mortality of hemodialysis patients.
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PMID:[Pharmacological and clinical trial data on a novel phosphate-binding polymer (sevelamer hydrochloride), a medicine for hyperphosphatemia in hemodialysis patients]. 1456 64

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.
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PMID:Safety of new phosphate binders for chronic renal failure. 1464 Jul 73

Phosphorus control remains a relevant clinical problem in dialysis patients. With age, however, serum phosphorus level decreases significantly because of a spontaneous decrease in protein intake. Older patients usually need lower doses of phosphorus binders. Nevertheless, hyperphosphataemia is observed in a quarter of patients aged >65 years. Phosphorus retention is related to an imbalance between phosphorus intake and removal by dialysis, and is usually aggravated when vitamin D analogues are employed. Hyperphosphataemia induces secondary hyperparathyroidism and the development of osteitis fibrosa. Recent publications describe an association between phosphorus retention and increased calcium and phosphorus product (Ca2+ x P), with significant progression of tissue calcification and higher mortality risk. Dietary intervention, phosphorus removal during dialysis and phosphorus binders are current methods for the management of hyperphosphataemia. However, the phosphorus removed by standard haemodialysis is insufficient to achieve a neutral phosphorus balance when protein intake is >50 g/day. Additional protein restriction may impose the risk of a negative protein balance. More frequent dialysis may help to control resistant hyperphosphataemia. Phosphorus binders constitute the mainstay of serum phosphorus level control in end-stage renal disease patients. Aluminium-based phosphorus binders, associated with toxic effects, have largely been substituted by calcium-based phosphorus binders. However, widespread use of calcium-based phosphorus binders has evidenced the frequent appearance of hypercalcaemia and long-term progressive cardiovascular calcification. Sevelamer, a relatively new phosphorus binder, has proved efficacious in lowering serum phosphorus and parathyroid hormone (PTH) levels without inducing hypercalcaemia. Furthermore, several investigators have reported that sevelamer may prevent progression of coronary calcification. However, its efficacy in severe cases of hyperphosphataemia remains to be confirmed in large series. There are no specific guidelines for phosphorus control in the elderly. Until more information is available, levels of mineral metabolites should be targeted in the same range as those recommended for the general population on dialysis (calcium 8.7-10.2 mg/dL, phosphorus 3.5-5.5 mg/dL and Ca2+ x P 50-55 mg2/dL2). PTH values over 120 ng/L help to avoid adynamic bone disease. Since elderly patients have a higher incidence of adynamic bone (which buffers less calcium) and vascular calcification, sevelamer should be the phosphorus binder of choice in this population; but sevelamer is costly and its long-term efficacy has not been definitively validated. Patients with low normal levels of calcium may receive calcium-based phosphorus binders with little risk. Patients with low values of PTH and high normal calcium should receive sevelamer. Tailored combinations of calcium-based phosphorus binders and sevelamer should be considered, and calcium dialysate concentration adjusted accordingly.
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PMID:Management of hyperphosphataemia in dialysis patients: role of phosphate binders in the elderly. 1497 34

Hyperphosphatemia is associated with soft-tissue calcification and bone disease. Nephrologists prescribe phosphate binders to decrease dietary phosphate absorption, reduce serum phosphorus concentrations, and minimize the risk for soft-tissue calcification and bone disease. Recent data suggest that the dose of calcium used as a phosphate binder may contribute to the risk for cardiovascular calcification. Chronic positive calcium balance from diet, dialysis, and calcium-based phosphate binders or intermittent hypercalcemia may favor precipitation of calcium and phosphate into tissues. Calcium suppresses parathyroid hormone (PTH) secretion and bone turnover, limiting the ability of bone to incorporate calcium and phosphorus. Sevelamer, a non-absorbed polymer, allows physicians to bind dietary phosphate and decrease serum phosphorus without unwanted absorption of metals or calcium or over-suppression of PTH. In a comparative trial, calcium-based phosphate binders were associated with progressive coronary artery and aortic calcification that was attenuated by sevelamer. The optimal phosphate binder is one that controls hyperphosphatemia prevents soft-tissue calcification and preserves bone health.
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PMID:Arterial calcification in chronic kidney disease. 1549 Mar 99

Hyperphosphatemia is one of the major causes of secondary hyperparathyroidism (II degrees HPT) in dialysis patients. Aluminum (Al) hydroxide was commonly used as a phosphate binder in Japan until the beginning of the 1990's, when it was replaced by calcium(Ca) compounds to eliminate undesirable side effects. Although Ca compounds are effective phosphate binders, the concomitant use of vitamin D derivatives can often result in hypercalcemia. For the reason, physicians today have been requesting phosphate binders that contain neither Al nor Ca. In this paper, we introduce several such phosphate binders. Sevelamer hydrocholoride (SH) is a new phosphate binder that contains neither Al nor Ca, and is not absorbed from the gastrointestinal tract. Several short-term clinical studies have established that SH is as efficient as calcium carbonate at lowering serum phosphorus (P) levels, with significant improvement in the Ca x P product and lipids metabolism. Furthermore, a long-term (52 weeks) study revealed that SH attenuated the progression of coronary and aortic calcification in hemodialysis (HD) patients. SH is considered a highly effective phosphate binder in protecting against the progression of II degrees HPT and cardiovascular death in HD patients.
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PMID:[Therapeutic agents for hyperphosphatemia]. 1577 44

Vascular calcifications are more frequent in dialysis patients than in the general population or in patients with cardiovascular disease (CVD) and normal renal function. The reasons for this high incidence are multiple; they include traditional factors such as hypertension, diabetes, dyslipidemia, and specific factors such as sodium overload, hyperomocysteinemia, chronic inflammation and oxidative stress, as well as mineral metabolism disturbances. Specifically, hyperphosphatemia and the elevated calcium (Ca) x phosphate product have been associated with an increased risk for the development of vascular calcification and death. Treatment with Ca salts can induce hypercalcemia, increased Ca x phosphate product and Ca overload. Sevelamer substitution for Ca salts has been documented to attenuate the progression of coronary artery and aortic calcification. A possible mechanism explaining this observation could be ongoing Ca loading related to oral Ca ingestion. Treatment with Ca salts could induce Ca overload, particularly in patients dialyzed against a high dialysate Ca (>1.5 mmol/L) solution, which is known to determine a positive dialysis balance. Conversely, an overall negative Ca balance can result from low Ca dialysate use (1.25 mmol/L) when the patients do not receive Ca supplements or vitamin D metabolites. Maintaining normal Ca and phosphate balances remains a primary goal in the management of dialysis patients. Control of hyperphopshataemia should be achieved either using Ca and aluminum-free phosphate binders, such as sevelamer, or Ca salts, alone or in combination, provided that a daily oral elemental Ca intake of 1.5 g is not exceeded.
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PMID:[Control of calcium and phosphate metabolism and prevention of vascular calcifications in uremic patients]. 1578 2


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