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

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

Aluminium- or calcium-based phosphate-binding agents traditionally have been used to treat hyperphosphataemia in patients with end-stage renal disease. Although these agents effectively lower serum phosphorus levels, they are associated with serious side effects. Aluminium-based agents are associated with bone toxicity, renal osteodystrophy and encephalopathy, and calcium-based agents increase the risk of hypercalcaemia and cardiovascular calcification. Consequently, there remains a need for new, safe and effective non-calcium-, non-aluminium-based alternative treatments. Fortunately, several new agents are now available or are in the late stages of development, including sevelamer hydrochloride and lanthanum carbonate. Although sevelamer hydrochloride represents a step forward in the management of hyperphosphataemia, it has several drawbacks and is far from being the ideal phosphate binder. Lanthanum carbonate is the most recent non-calcium, non-aluminium phosphate binder to be developed for the treatment of hyperphosphataemia. Animal studies have shown it to be as effective as aluminium, without the associated toxicity. In clinical studies, lanthanum carbonate significantly reduced serum phosphorus levels, compared with placebo. It shows a similar efficacy to calcium carbonate in controlling serum phosphorus levels, but requires lower doses. In addition, lanthanum carbonate is at least as well tolerated as calcium carbonate, but is not associated with hypercalcaemia. Importantly, it has a positive effect on bone histology, with no evolution towards low bone turnover. Lanthanum carbonate, therefore, moves closer to the ideal phosphate binder.
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PMID:Improving phosphate-binder therapy as a way forward. 1512 50

Controlling serum phosphorus levels in patients with renal failure is critical. The use of oral phosphate-binding agents is universal for patients with end-stage kidney disease to reduce phosphate absorption. The therapeutic goal is to reduce serum phosphorus levels without disturbing calcium homeostasis or promoting accumulation of potentially toxic elements from the medication. Aluminum hydroxide effectively reduces serum phosphorus, but has largely been abandoned as a first-line phosphate binder because of hazards associated with metal absorption and tissue accumulation. Traditional calcium-based phosphate binders tend to promote hypercalcemia and calcium overloading, and are linked to accelerated cardiovascular calcification. Interest in aluminum-free, calcium-free phosphate-binding agents continues to grow. Sevelamer hydrochloride, a metal-free, calcium-free hydrogel, is not absorbed, has been proven safe and efficacious in controlling serum phosphorus, and is associated with attenuated progression of cardiovascular calcification. Lanthanum carbonate is a newer aluminum-free, calcium-free phosphate-binding agent. Lanthanum is a rare-earth trace metal with industrial and agricultural applications. As a therapeutic, this metal-based binder appears effective in reducing serum phosphorus, yet concerns remain about lanthanum accumulation in tissues during long-term oral administration. Similar to the metal aluminum, lanthanum is absorbed in the intestine and accumulates in body tissues, especially in the liver, bone, muscle, kidney, and brain. Moreover, the rate of intestinal absorption of lanthanum is enhanced in chronic renal failure. Our experience with aluminum hydroxide suggests caution regarding the long-term use of another metal-based agent that displays enhanced absorption in the uremic state and progressive tissue accumulation.
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PMID:Lanthanum carbonate as a first-line phosphate binder: the "cons". 1763 23

Cardiovascular mortality is the leading cause of death in the uremic patient. Hyperphosphatemia is considered an independent risk factor associated with cardiovascular morbidity and mortality in dialysis patients. As phosphate control is not efficient with diet or dialysis, phosphate binders are commonly prescribed in patients with chronic renal failure. Aluminum salts, the first phosphate binders, even if effective, have several side effects due to their deposition in CNS, bone and hematopoietic cells. Calcium-containing phosphate binders, used in the last 15 years, increase total body calcium load and may exacerbate metastatic calcification, thus, increasing the risk of cardiovascular mortality. Recently two new compounds non-aluminum and non-calcium phosphate binders, sevelamer hydrochloride and lanthanum carbonate, have been introduced. Sevelamer, besides the effect on phosphate, has been associated with reduction of coronary and aortic calcification and with other pleiotropic effects especially on lipid metabolism. Lanthanum carbonate has similar phosphate control to calcium-based binders with less incidence of hypercalcemia but long-term clinical studies are needed for testing long-term exposure. Recently the authors found in dialysis patients, that salivary phosphorus correlated with serum phosphorus. Therefore, they supposed that the use of salivary phosphate binders could reduce its absorption and represent a chance for reducing the serum phosphate concentration in uremic patients.
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PMID:Emerging drugs for hyperphosphatemia. 1787 64

Lanthanum is an element belonging to the group called rare earths. Due to its low solubility, lanthanum carbonate has been widely studied as an intestinal phosphate binder. The results of different clinical trials show that it is an effective and well-tolerated phosphate binder used in monotherapy. Serum phosphate levels are controlled in approximately 70% of patients at 5 years without causing hypercalcemia. The only significant adverse effects observed are a low percentage of gastrointestinal disturbances (6%). Lanthanum carbonate does not alter serum values of liposoluble vitamins or affect the pharmacokinetics of digoxin, warfarin, furosemide, phenytoin, ACE inhibitors or beta-blockers. However, it does alter the pharmacokinetics of ciprofloxacin (quinolones in general), tetracyclines and doxycycline. Lanthanum carbonate (Fosrenol) is available in Spain as 500 mg, 750 mg, and 1,000 mg chewable tablets, which should not be swallowed without chewing to avoid loss of efficacy. The initial dose recommended by the WHO is 2,250 mg/day, which is equivalent to one 750 mg at each meal. Lanthanum carbonate or lanthanum phosphate can be clearly visualized on a plain x-ray of the abdomen in patients who have recently ingested it. In summary, lanthanum carbonate is a widely studied potent phosphate binder, which offers the possibility of improving control of serum phosphate in patients with chronic kidney disease, without significant side effects. The fact that it is available as chewable tablets and that the number of daily tablets required has been significantly reduced will probably facilitate better patient compliance.
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PMID:[Lanthanum carbonate in clinical practice]. 1884 14

In 1960s and 1970s when hemodialysis therapy was started in Japan, calcium carbonate was used as a phosphate binder and as the purpose of calcium supplement. Aluminum preparations were widely used in Japan, Europe and United states since the end of 1970s, when these drugs were reported as a strong phosphate binder. After that, some adverse effects such as encephalopathy and bone lesions attributed to Aluminum administration have become serious problems in dialysis patients. As a result, Aluminum administration was prohibited in 1992 in Japan. Oral vitamin D pulse therapy was developed in 1990s as a treatment for secondary hyperparathyroidism in Japan, hypercalcemia have been occurred easily by combination use of vitamin D preparations and calcium carbonate. Since the 2000s, various complications, such as ectopic calcifications, cardiovascular diseases, and reduced life expectancy, which are associated with hypercalcemia and hyperphosphatemia have been clarified. Therefore, sevelamer hydrochrolide, that is non calcium phosphate binder, became available from 2003. Moreover, Lanthanum carbonate, that is another type of non calcium phosphate binder, was effective in Europe and United States, and also developing in Japan. However, there are not any phosphate binders which solved all clinical problems such as phosphate adsorptive power, digestive symptoms, and organ accumulation.
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PMID:[Management of phosphate in chronic kidney disease--Chemistry and history of phosphate binder]. 1918 59

Lanthanum (La) is a rare-earth element in transition Group III b of the periodic table. It is a ductile and malleable, silvery-white metal, soft enough to be cut with a knife. Lanthanum carbonate (La2[CO3]3) is the most recent non-calcium, non-aluminum phosphate binder to be developed for the treatment of hyperphosphatemia. This drug has already been registered and available in the US and EU. Precilinical studies have shown that it is as effective as aluminium, without the associated toxicity, and is minimally absorbed. In clinical studies (La2[CO3]3) has a similar ability to calcium carbonate in controlling serum phosphate level without hypercalcemia. In this review I would like to summarize the pharmacodynamic and pharmacokinetic profile of this new phosphate binder (La2[CO3]3) which will be registered in our country in the near future.
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PMID:[Pharmacodynamic and pharmacokinetic profile of lanthanum carbonate]. 1918 61

Hyperphosphatemia is an inevitable consequence of end stage chronic kidney disease and is present in the majority of dialysis patients. Recent observational data has associated hyperphosphatemia with increased cardiovascular mortality among dialysis patients. Dietary restriction of phosphate and current dialysis prescription practices are not enough to maintain serum phosphate levels within the recommended range so that the majority of dialysis patients require oral phosphate binders. Unfortunately, conventional phosphate binders are not reliably effective and are associated with a range of limitations and side effects. Aluminium-containing agents are highly efficient but no longer widely used because of well established and proven toxicity. Calcium based salts are inexpensive, effective and most widely used but there is now concern about their association with hypercalcemia and vascular calcification. Sevelamer hydrochloride is associated with fewer adverse effects, but a large pill burden and high cost are limiting factors to its wider use. In addition, the efficacy of sevelamer as a monotherapy in lowering phosphate to target levels in severe hyperphosphatemia remains debatable. Lanthanum carbonate is a promising new non-aluminium, calcium-free phosphate binder. Preclinical and clinical studies have demonstrated a good safety profile, and it appears well tolerated and effective in reducing phosphate levels in dialysis patients. Its identified adverse events are apparently mild to moderate in severity and mostly GI related. It appears to be effective as a monotherapy, with a reduced pill burden, but like sevelamer, it is significantly more expensive than calcium-based binders. Data on its safety profile over 6 years of treatment are now available.
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PMID:Phosphate binding therapy in dialysis patients: focus on lanthanum carbonate. 1920 70

Hyperphosphatemia is an inevitable consequence of end-stage chronic kidney disease and is present in the majority of dialysis patients. Hyperphosphatemia is observationally and statistically associated with increased cardiovascular mortality among dialysis patients. Dietary restriction of phosphate and current dialysis modalities are not sufficiently effective to maintain serum phosphate levels within the recommended range, so the majority of dialysis patients require oral phosphate binders. However, the benefits of achieving the recommended range have yet to be shown prospectively. Unfortunately, conventional phosphate binders are not reliably effective and are associated with a range of limitations and side effects. Aluminum-containing agents are highly efficient but no longer widely used because of proven toxicity. Calcium-based salts are inexpensive, effective, and most widely used, but there is now concern about their association with hypercalcemia and vascular calcification. Sevelamer hydrochloride is associated with fewer adverse effects, but a large pill burden and high cost are limiting factors to its wider use. Lanthanum carbonate is another non-aluminum, calcium-free phosphate binder. Preclinical and clinical studies have shown a good safety profile, and it appears to be well tolerated and effective in reducing phosphate levels in dialysis patients; however, it is similarly expensive. Data on its safety profile over 6 years of treatment are now published. Achievement of opinion-based guidelines appears to have become an end in itself. Dialysis patient outcomes are worse than outcomes for many types of cancer, yet prospective, outcome-based randomized controlled trials are not being undertaken for reasons that are difficult to explain.
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PMID:Oral phosphate binders. 1927 54

Orally administered lanthanum carbonate (Fosrenol) dissociates in the acid environment of the upper gastrointestinal tract to release the cation lanthanum, which then binds dietary phosphate. Lanthanum carbonate was effective in reducing levels of serum phosphate and serum calcium x phosphate product and then maintaining these levels within target ranges for up to 6 years in adult patients with end-stage renal disease (ESRD) on haemodialysis or peritoneal dialysis. The reduction in serum phosphate levels with lanthanum carbonate was generally similar to that with calcium carbonate or sevelamer hydrochloride. This agent was generally well tolerated, with the most frequently reported adverse events being gastrointestinal in nature and occurring at a similar rate to that with calcium carbonate. However, lanthanum carbonate was associated with fewer episodes of hypercalcaemia than calcium carbonate. Overall, lanthanum carbonate is a valuable option for the reduction of serum phosphate levels in patients with ESRD on haemodialysis or peritoneal dialysis.
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PMID:Lanthanum carbonate: a review of its use in lowering serum phosphate in patients with end-stage renal disease. 1985 31


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