Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients
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, de...
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doaj-fefa61c883f24454bf5427e7db6300a52020-11-24T21:13:30ZengHindawi LimitedInternational Journal of Endocrinology1687-83371687-83452015-01-01201510.1155/2015/406269406269Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis PatientsNaoko Otani-Takei0Takahiro Masuda1Tetsu Akimoto2Sumiko Honma3Yuko Watanabe4Kazuhiro Shiizaki5Takuya Miki6Eiji Kusano7Yasushi Asano8Makoto Kuro-o9Daisuke Nagata10Division of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, JapanDivision of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, JapanDivision of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, JapanDepartment of Nephrology, Japanese Red Cross Koga Hospital, Koga, Ibaraki, JapanDivision of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, JapanDivision of Anti-Aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, JapanDivision of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, JapanDivision of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, JapanDepartment of Nephrology, Japanese Red Cross Koga Hospital, Koga, Ibaraki, JapanDivision of Anti-Aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, JapanDivision of Nephrology, Department of Internal Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, JapanKlotho 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.http://dx.doi.org/10.1155/2015/406269 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Naoko Otani-Takei Takahiro Masuda Tetsu Akimoto Sumiko Honma Yuko Watanabe Kazuhiro Shiizaki Takuya Miki Eiji Kusano Yasushi Asano Makoto Kuro-o Daisuke Nagata |
spellingShingle |
Naoko Otani-Takei Takahiro Masuda Tetsu Akimoto Sumiko Honma Yuko Watanabe Kazuhiro Shiizaki Takuya Miki Eiji Kusano Yasushi Asano Makoto Kuro-o Daisuke Nagata Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients International Journal of Endocrinology |
author_facet |
Naoko Otani-Takei Takahiro Masuda Tetsu Akimoto Sumiko Honma Yuko Watanabe Kazuhiro Shiizaki Takuya Miki Eiji Kusano Yasushi Asano Makoto Kuro-o Daisuke Nagata |
author_sort |
Naoko Otani-Takei |
title |
Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients |
title_short |
Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients |
title_full |
Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients |
title_fullStr |
Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients |
title_full_unstemmed |
Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients |
title_sort |
association between serum soluble klotho levels and mortality in chronic hemodialysis patients |
publisher |
Hindawi Limited |
series |
International Journal of Endocrinology |
issn |
1687-8337 1687-8345 |
publishDate |
2015-01-01 |
description |
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. |
url |
http://dx.doi.org/10.1155/2015/406269 |
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