title: Phosphate is a vascular toxin.
abstract: Elevated phosphate (P) levels are seen in advanced renal failure and, together with dysregulated calcium, parathyroid hormone and vitamin D levels, contribute to the complex of chronic kidney disease-mineral and bone disease (CKD-MBD). Converging evidence from in vitro, clinical and epidemiological studies suggest that increased P is associated with vascular calcification and mortality. When vessels are exposed to high P conditions in vitro, they develop apoptosis, convert to bone-like cells and develop extensive calcification. Clinical studies in children on dialysis show that high P is associated with increased vessel wall thickness, arterial stiffness and coronary calcification. Epidemiological studies in adult dialysis patients demonstrate a significant and independent association between raised P and mortality. Importantly, raised P is associated with cardiovascular changes even in pre-dialysis CKD, and also in subjects with normal renal function but high P. All P binders can effectively reduce serum P, and this decrease is linked to improved survival. Raised serum P triggers the release of fibroblast growth factor 23 (FGF-23), which has the beneficial effect of increasing P excretion in early CKD, but is increased several 1,000-fold in dialysis, and may be an independent cardiovascular risk factor. Both FGF-23 and its co-receptor Klotho may have direct effects on the vasculature leading to calcification. Fascinatingly, disturbances in FGF-23-Klotho and raised P have also been associated with premature aging. These data suggest that high P levels have adverse vascular effects and that maintaining the serum P levels in the normal range reduces cardiovascular risk and mortality.
authors.affiliation: Renal Unit, Great Ormond Street Hospital for Children, Great Ormond Street, London, WC1N 3JH, UK. Rukshana.Shroff@gosh.nhs.uk
authors.forename: Rukshana
authors.initials: R
authors.lastname: Shroff
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D054559:Hyperphosphatemia / Q000453:epidemiology* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D000090265:Klotho Proteins; D010710:Phosphates / Q000378:metabolism*; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000378:metabolism / Q000503:physiopathology; D012307:Risk Factors; D061205:Vascular Calcification / Q000453:epidemiology* / Q000378:metabolism / Q000503:physiopathology
chemical_list: C000717427:FGF23 protein, human; D010710:Phosphates; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins