Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperphosphatemia is a common serious complication of chronic renal diseases, which needs appropriate continuous treatment in order to avoid ominous side effects. Therefore, oral chelating agents able to avoid phosphate absorption by the gut are mandatory. In the past, Aluminium salts, and more recently Calcium and Magnesium salts, and a synthetic resin polyallylamine hydrochloride have been employed, but Aluminium was later abandoned, because it has been a silent killer of many uremic patients, due to subtle absorption eventually leading to toxicity on Central Nervous System and bone, with allucinations, seizures, dementia, and osteomalacia, bone pain, fracturing osteodystrophy, and death. Recently, a new chelating agent able to bind dietary phosphate, namely Lanthanum carbonate has been introduced, with a proven efficacy profile for short-term treatment. However, after careful examination of the very few scientific papers available to date, we strongly advise caution before adopting, at present, lanthanum carbonate as a phosphate binder in uremic patients. In fact, notwithstanding minimized, some data are worrying: first, Lanthanum ions are absorbed, though at a minimal extent, by human gut; 2) pharmacokinetic evaluations show a greater exposure to Lanthanum in uremic patients;3) Lanthanum concentration is increased tenfold in blood and fivefold in bone after short-term supplementation in uremic patients; 4) there is no proofs that Lanthanum cannot cross the blood brain barrier in uremic patients; 5)Lanthanum has many biological effects and is potentially highly toxic. The Aluminum story should serve as cautionary tale when considering the use of new metal ions.
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PMID:Blast from the past: the aluminum's ghost on the lanthanum salts. 1602 63

(1) In dialysis patients with chronic renal failure, hyperphosphataemia can cause osteorenal dystrophy, leading to bone pain, fractures and excess cardiovascular mortality. In addition to a low-phosphorus diet and dialysis, phosphorus chelators are usually needed to control blood phosphorus levels. The first choice is calcium carbonate, and sevelamer is an alternative. (2) Lanthanum carbonate, a phosphorus chelator, is now also licensed for the treatment of hyperphosphataemia in dialysis patients with chronic renal failure. (3) In addition to three dose-finding placebo-controlled studies, clinical evaluation includes 2 comparative randomised unblinded trials: one 6-month trial versus calcium carbonate and a 2-year trial versus other phosphorus chelators. During these trials, lanthanum was no more effective than the comparators in terms of effects on the mortality rate, incidence of fractures, or blood phosphorus level. (4) During these trials, adverse events attributed to treatment were more frequent with lanthanum than with the other phosphorus chelators. The main problems were gastrointestinal disorders (nausea, vomiting, diarrhoea, constipation and abdominal pain), headaches, seizures, and encephalopathy. (5) The accumulation of lanthanum in the bones and brain is troubling. The known long-term adverse effects of aluminium, another trivalent cation with weak gastrointestinal absorption, suggest that caution is also required with lanthanum. (6) In practice, when a phosphorus chelator is needed to treat hyperphosphataemia in dialysis patients with chronic renal failure, calcium carbonate is the first choice and sevelamer remains the best alternative.
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PMID:Lanthanum: new drug. Hyperphosphataemia in dialysis patients: more potential problems than benefits. 1745 39