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

Naoko Otani-Takei, Takahiro Masuda, Tetsu Akimoto, Sumiko Honma, Yuko Watanabe, Kazuhiro Shiizaki, Takuya Miki, Eiji Kusano, Yasushi Asano, Makoto Kuro-O, Daisuke Nagata

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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 6.7±5.4 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.

Original languageEnglish (US)
Article number406269
JournalInternational Journal of Endocrinology
StatePublished - 2015

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems


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