title: Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients.
abstract: 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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Otani-Takei
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Akimoto
authors.affiliation: Department of Nephrology, Japanese Red Cross Koga Hospital, Koga, Ibaraki, Japan.
authors.forename: Sumiko
authors.initials: S
authors.lastname: Honma
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Division of Anti-Aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Shiizaki
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Miki
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kusano
authors.affiliation: Department of Nephrology, Japanese Red Cross Koga Hospital, Koga, Ibaraki, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Asano
authors.affiliation: Division of Anti-Aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kuro-O
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nagata