TY - JOUR
T1 - A phosphate-centric paradigm for pathophysiology and therapy of chronic kidney disease
AU - Kuro-O, Makoto
N1 - Funding Information:
This supplement was supported by a grant from the 58th Annual Meeting of the Japanese Society for Dialysis Therapy.
PY - 2013/12/2
Y1 - 2013/12/2
N2 - Extracellular phosphate is toxic to the cell at high concentrations. When the phosphate level is increased in the blood by impaired urinary phosphate excretion, premature aging ensues. When the phosphate level is increased in the urine by dietary phosphate overload, this may lead to kidney damage (tubular injury and interstitial fibrosis). Extracellular phosphate exerts its cytotoxicity when it forms insoluble nanoparticles with calcium and fetuin-A, referred to as calciprotein particles (CPPs). CPPs are highly bioactive ligands that can induce various cellular responses, including osteogenic transformation of vascular smooth muscle cells and cell death in vascular endothelium and renal tubular epithelium. CPPs are detected in the blood of animal models and patients with chronic kidney disease (CKD) and associated with adaptation of the endocrine axes mediated by fibroblast growth factor-23 (FGF23) and Klotho that regulate mineral metabolism and aging. These observations have raised the possibility that CPPs may contribute to the pathophysiology of CKD. This notion, if validated, is expected to provide new diagnostic and therapeutic targets for CKD.
AB - Extracellular phosphate is toxic to the cell at high concentrations. When the phosphate level is increased in the blood by impaired urinary phosphate excretion, premature aging ensues. When the phosphate level is increased in the urine by dietary phosphate overload, this may lead to kidney damage (tubular injury and interstitial fibrosis). Extracellular phosphate exerts its cytotoxicity when it forms insoluble nanoparticles with calcium and fetuin-A, referred to as calciprotein particles (CPPs). CPPs are highly bioactive ligands that can induce various cellular responses, including osteogenic transformation of vascular smooth muscle cells and cell death in vascular endothelium and renal tubular epithelium. CPPs are detected in the blood of animal models and patients with chronic kidney disease (CKD) and associated with adaptation of the endocrine axes mediated by fibroblast growth factor-23 (FGF23) and Klotho that regulate mineral metabolism and aging. These observations have raised the possibility that CPPs may contribute to the pathophysiology of CKD. This notion, if validated, is expected to provide new diagnostic and therapeutic targets for CKD.
KW - Calciprotein particle (CPP)
KW - Fibroblast growth factor-23 (FGF23)
KW - Klotho
KW - Phosphate restriction
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U2 - 10.1038/kisup.2013.88
DO - 10.1038/kisup.2013.88
M3 - Review article
C2 - 25019024
AN - SCOPUS:84896702624
SN - 2157-1724
VL - 3
SP - 420
EP - 426
JO - Kidney International Supplements
JF - Kidney International Supplements
IS - 5
ER -