Document Detail


Safety of new phosphate binders for chronic renal failure.
MedLine Citation:
PMID:  14640773     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Mahmoud Loghman-Adham
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Drug safety : an international journal of medical toxicology and drug experience     Volume:  26     ISSN:  0114-5916     ISO Abbreviation:  Drug Saf     Publication Date:  2003  
Date Detail:
Created Date:  2003-12-03     Completed Date:  2004-04-15     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  9002928     Medline TA:  Drug Saf     Country:  New Zealand    
Other Details:
Languages:  eng     Pagination:  1093-115     Citation Subset:  IM    
Affiliation:
mloghman@att.net
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MeSH Terms
Descriptor/Qualifier:
Aluminum / therapeutic use
Calcium / therapeutic use
Epoxy Compounds / therapeutic use
Humans
Iron Compounds / therapeutic use
Kidney Failure, Chronic / therapy*
Lanthanum / therapeutic use
Magnesium / therapeutic use
Phosphates / blood*
Polyamines
Polyethylenes / therapeutic use
Renal Dialysis
Safety
Chemical
Reg. No./Substance:
0/Epoxy Compounds; 0/Iron Compounds; 0/Phosphates; 0/Polyamines; 0/Polyethylenes; 182683-00-7/sevelamer; 7429-90-5/Aluminum; 7439-91-0/Lanthanum; 7439-95-4/Magnesium; 7440-70-2/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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