Oral phosphate binders: history and prospects.
The use of an oral phosphate binder is a promising and most practical strategy for the prevention of vascular calcification in patients with chronic kidney disease (CKD). To secure the safety: 1) the oral phosphate binder must not cause adverse effects in the gastrointestinal tract; 2) the oral phosphate binder should be non-absorbable or barely absorbable through the gastrointestinal tract, or 3) if partially absorbed through the gastrointestinal tract, it must be eliminated from circulation through a pathway other than urinary excretion, and 4) even if it accumulates in the body, it should not cause organ dysfunctions. Metal salt type oral phosphate binder is the most classical type of oral phosphate binders that includes aluminum hydroxide gel and lanthanum carbonate. These oral phosphate binders effectively adsorb phosphate ions, however, have a potential risk for accumulation and intoxication. Calcium salt type oral phosphate binder was the most widely prescribed oral phosphate binder in the last decade but is now believed to exert potential harm, favoring progression of vascular calcification through excessive intestinal calcium load. However, recent studies failed to detect an inferiority of calcium salt type oral phosphate binders as compared to non-calcium salt type oral phosphate binders in terms of mortality and/or morbidity of hemodialysis patients. Polymerized resin type is a safe and relatively effective oral phosphate binder, which is supported by many clinical evidences. However, it sometimes causes severe constipation, especially in Japanese patients. Among metal compound type oral phosphate binder, other promising compounds include boehmite-type aluminum and hydrotalcite-like compounds but they are not yet available in the clinical setting.
Division of Nephrology and Intensive Care Medicine, Niigata University Medical and Dental Hospital, Niigata, 951-8510, Japan. jjkaz@med.niigata-u.ac.jp
Junichiro James
JJ
Kazama
D000284:Administration, Oral; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002614:Chelating Agents / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D010710:Phosphates / Q000008:administration & dosage*; D011108:Polymers / Q000494:pharmacology; D012117:Resins, Synthetic / Q000494:pharmacology
D002614:Chelating Agents; D010710:Phosphates; D011108:Polymers; D012117:Resins, Synthetic; D002118:Calcium