title: Gastrointestinal phosphate handling in CKD and its association with cardiovascular disease.
abstract: Increases in serum concentrations of parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) and ultimately phosphate and decreases in 1,25-dihydroxyvitamin D level are thought to play a central role in the progressive nature of kidney disease and the development of cardiovascular disease in patients with chronic kidney disease. The initial changes in PTH and FGF-23 levels are adaptive to maintain serum phosphate concentration and phosphate load within defined levels by increasing urinary excretion of phosphate. Less well appreciated is the unanticipated finding that absorption of phosphate from the gastrointestinal tract is not downregulated in chronic kidney disease. This maladaptive response maintains higher levels of phosphate absorption, thereby contributing to the phosphate burden. Moreover, in response to a low-phosphate diet, as often is prescribed to such patients, gut phosphate absorption may be enhanced, undermining the potential beneficial effects of this intervention. Given the poor response to limiting phosphate intake and the use of phosphate binders, we suggest that research efforts be oriented toward better understanding of the factors that affect phosphate absorption in the gastrointestinal tract and the development of agents that directly inhibit phosphate transporters in the small intestine and/or their associated binding proteins.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD; Department of Veteran Affairs, Baltimore, MD. Electronic address: eweinman@medicine.umaryland.edu.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Weinman
authors.forename: Paul D
authors.initials: PD
authors.lastname: Light
authors.forename: Wadi N
authors.initials: WN
authors.lastname: Suki
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000378:metabolism; D004032:Diet; D018450:Disease Progression; D000089703:Fibroblast Growth Factor-23; D041981:Gastrointestinal Tract / Q000378:metabolism*; D006801:Humans; D054559:Hyperphosphatemia / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D010349:Patient Compliance; D028044:Phosphate-Binding Proteins / Q000627:therapeutic use; D010710:Phosphates / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000378:metabolism*; D012307:Risk Factors
chemical_list: C000717427:FGF23 protein, human; D028044:Phosphate-Binding Proteins; D010710:Phosphates; D000089703:Fibroblast Growth Factor-23
keywords: Gastrointestinal absorption of phosphate in chronic kidney disease (CKD); phosphate burden; treatment strategies in chronic kidney disease (CKD)