title: Phosphate: a stealthier killer than previously thought?
abstract: The kidneys excrete excess dietary phosphate, and patients with chronic kidney disease may suffer from phosphate overload and hyperphosphatemia. In chronic kidney disease, hyperphosphatemia has emerged as a risk factor for vascular calcification, cardiovascular mortality, left ventricular hypertrophy, and progression of chronic kidney disease. Serum phosphate at the upper limits of normal has also been associated with adverse outcomes in patients with relatively preserved kidney function. Of note, hyperphosphatemia is not a sensitive indicator of phosphate overload. In this regard, increased circulating fibroblast growth factor-23, a phosphatonin that is released in response to phosphate overload, is independently associated with adverse outcomes in patients with and without chronic kidney disease. Direct effects of extracellular phosphate on vascular calcification or cardiovascular cell biology; adverse consequences of adaptive mechanisms activated to limit phosphate overload, such as left ventricular hypertrophy induced by fibroblast growth factor-23; or epidemiological associations of additional cardiovascular risk factors with chronic kidney disease may underlie these observations. We now review the pathophysiology of phosphate, its relationship with cardiovascular outcomes, the potential consequences for patient care related to dietary phosphate and phosphate binders, and the clinical relevance for patients without overt chronic kidney disease.
authors.affiliation: Nephrology Department, IIS-Fundación Jiménez Díaz, Universidad Autónoma de Madrid, Madrid. egonzalezpa@senefro.org
authors.forename: Emilio
authors.initials: E
authors.lastname: Gonzalez-Parra
authors.forename: Jose
authors.initials: J
authors.lastname: Tuñón
authors.forename: Jesus
authors.initials: J
authors.lastname: Egido
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D000818:Animals; D000830:Animals, Laboratory; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D002114:Calcinosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D002130:Calcium Phosphates / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004195:Disease Models, Animal; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D006801:Humans; D054559:Hyperphosphatemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D010710:Phosphates / Q000009:adverse effects / Q000378:metabolism*; D016226:Phosphorus, Dietary / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology; D006435:Renal Dialysis / Q000009:adverse effects; D000069603:Sevelamer; D059289:Vascular Stiffness / Q000187:drug effects
chemical_list: D002130:Calcium Phosphates; D002614:Chelating Agents; D010710:Phosphates; D016226:Phosphorus, Dietary; D011073:Polyamines; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; C020243:calcium phosphate; D000069603:Sevelamer