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International Journal of Endocrinology
Volume 2015, Article ID 406269, 10 pages
Research Article

Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients

1Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
2Department of Nephrology, Japanese Red Cross Koga Hospital, Koga, Ibaraki, Japan
3Division of Anti-Aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan

Received 26 July 2015; Revised 4 October 2015; Accepted 13 October 2015

Academic Editor: Darío A. Castroviejo

Copyright © 2015 Naoko Otani-Takei et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Klotho is a single-pass transmembrane protein predominantly expressed in the kidney. The extracellular domain of Klotho is subject to ectodomain shedding and is released into the circulation as a soluble form. Soluble Klotho is also generated from alternative splicing of the Klotho gene. In mice, defects in Klotho expression lead to complex phenotypes resembling those observed in dialysis patients. However, the relationship between the level of serum soluble Klotho and overall survival in hemodialysis patients, who exhibit a state of Klotho deficiency, remains to be delineated. Here we prospectively followed a cohort of 63 patients with a mean duration of chronic hemodialysis of years for a median of 65 months. Serum soluble Klotho was detectable in all patients (median 371 pg/mL, interquartile range 309–449). Patients with serum soluble Klotho levels below the lower quartile (<309 pg/mL) had significantly higher cardiovascular and all-cause mortality rates. Furthermore, the higher all-cause mortality persisted even after adjustment for confounders (hazard ratio 4.14, confidence interval 1.29–13.48). We conclude that there may be a threshold for the serum soluble Klotho level associated with a higher risk of mortality.