期刊
NEFROLOGIA
卷 38, 期 3, 页码 250-257出版社
SOC ESPANOLA NEFROLOGIA DR RAFAEL MATESANZ
DOI: 10.1016/j.nefro.2017.07.005
关键词
Vascular calcification; Pyrophosphate; Chronic kidney disease; Haemodialysis; Hydroxyapatite
资金
- Spanish Ministerio de Economia y Competitividad [SAF-2014-60699-JIN]
- Instituto de Salud Carlos III (Sara Borrell postdoctoral contract) [CD14/00198]
- Foundation SENEFRO (Spanish Nephrology Society)
- FEDER funds [PI14/00386]
Vascular calcification is a pathology characterized by the deposition of calcium-phosphate in cardiovascular structures, mainly in the form of hydroxyapatite crystals, resulting in ectopic calcification. It is correlated with increased risk of cardiovascular disease and myocardial infarction in diabetic patients and in those with chronic kidney disease (CKD). Vascular smooth muscle cells are sensitive to changes in inorganic phosphate (Pi) levels. They are able to adapt and modify some of their functions and promote changes which trigger calcification. Pi is regulated by parathyroid hormone and 1,25-dihydroxyvitamin D. Changes in the transport of Pi are the primary factor responsible for the regulation of Pi homeostasis and the calcification process. Synthesis of calcification inhibitors is the main mechanism by which cells are able to prevent vascular calcification. Extracellular pyrophosphate (PPi) is a potent endogenous inhibitor of calcium-phosphate deposition both in vivo and in vitro. Patients with CKD show lower levels of PPi and increased activity of the enzyme alkaline phosphatase. Numerous enzymes implicated in the metabolism of PPi have been associated with vascular calcifications. PPi is synthesized from extracellular ATP by nucleotide pyrophosphatase/phosphodiesterase from extracellular ATP hydrolysis. PPi is hydrolyzed into Pi by tissue-nonspecific alkaline phosphatase. ATP can be hydrolyzed to Pi via the ectonucleoside triphosphate diphosphohydrolase family. All these enzymes must be in balance, thereby preventing calcifications. However, diseases like CKD or diabetes induce alterations in their levels. Administration of PPi could open up new treatment options for these patients. (C) 2017 Sociedad Espanola de Nefrologia. Published by Elsevier Espana, S.L.U.
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