Soluble klotho as biomarker of vascular dysfunction in chronic kidney disease

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Abstract

Disturbed mineral metabolism in patients with chronic kidney disease (CKD), known as CKD-mineral and bone disorder (CKD-MBD), is associated with bone disease as well as a high risk of cardiovascular disease (CVD) and reduced patient survival due to the development of vascular calcification. Hyperphosphatemia is a risk factor for vascular calcification, CVD, and mortality. The fibroblast growth factor-23 (FGF-23)-Klotho system plays a key role in the regulation of mineral metabolism. Klotho was originally identified as an aging-suppressor gene and is predominantly expressed in the distal renal tubules. Klotho exists in two forms: membrane Klotho functions as an obligate coreceptor for FGF-23 in the kidneys and parathyroid gland, while secreted Klotho functions as a humoral factor with antiaging, renoprotective, and cardiovascular protective properties. The urinary and circulating Klotho levels have been found to be decreased in patients with acute kidney injury and CKD, and experimental studies have shown that Klotho has beneficial effects on the vascular system. Furthermore, Klotho exerts pleiotropic effects on the endothelium, including anti-inflammatory, antithrombotic, and vasodilatory effects, and increases the availability of nitric oxide, and Klotho deficiency is associated with the vascular calcification observed in CKD patients. Therefore, soluble Klotho has the potential to serve as a biomarker for diagnosing early CKD and predicting the progression of both CKD and CVD. The renoprotective and cardiovascular protective functions of Klotho have also led researchers to hope that this protein may be used as a therapeutic agent for improving the kidney function and CVD.

Original languageEnglish
Title of host publicationGeneral Methods in Biomarker Research and their Applications
PublisherSpringer International Publishing
Pages891-917
Number of pages27
Volume2-2
ISBN (Electronic)9789400776968
ISBN (Print)9789400776951
DOIs
Publication statusPublished - Sep 2 2015

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Kitagawa, M., Sugiyama, H., Nakamura, K., Ito, H., & Makino, H. (2015). Soluble klotho as biomarker of vascular dysfunction in chronic kidney disease. In General Methods in Biomarker Research and their Applications (Vol. 2-2, pp. 891-917). Springer International Publishing. https://doi.org/10.1007/978-94-007-7696-8_44