Open Access Highly Accessed Research article

Characteristics of urinary and serum soluble Klotho protein in patients with different degrees of chronic kidney disease

Tetsu Akimoto1*, Hiromichi Yoshizawa1, Yuko Watanabe1, Akihiko Numata1, Tomoyuki Yamazaki1, Eri Takeshima1, Kana Iwazu1, Takanori Komada1, Naoko Otani1, Yoshiyuki Morishita1, Chiharu Ito1, Kazuhiro Shiizaki2, Yasuhiro Ando1, Shigeaki Muto1, Makoto Kuro-o2 and Eiji Kusano1

Author affiliations

1 Division of Nephrology, Department of Internal Medicine, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-Shi, TOCHIGI, 329-0498, Japan

2 Department of Pathology, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX, 75390-9072, USA

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Citation and License

BMC Nephrology 2012, 13:155  doi:10.1186/1471-2369-13-155

Published: 23 November 2012



Klotho is a single-pass transmembrane protein, which appears to be implicated in aging. The purpose of the present study was to characterize the relationship between the soluble Klotho level and renal function in patients with various degrees of chronic kidney disease (CKD).


The levels of soluble Klotho in the serum and urine obtained from one hundred thirty-one CKD patients were determined by a sandwich enzyme-linked immunosorbent assay system.


The amount of urinary excreted Klotho during the 24 hr period ranged from 1.6 to 5178 ng/day (median 427 ng/day; interquartile range [IR] 56.8-1293.1), and the serum Klotho concentration ranged from 163.9 to 2123.7 pg/ml (median 759.7 pg/ml; IR 579.5-1069.1). The estimated glomerular filtration rate (eGFR) was significantly correlated with the log-transformed values of the amount of 24 hr urinary excreted Klotho (r = 0.407, p < 0.01) and the serum Klotho levels (r = 0.232, p < 0.01). However, a stepwise multiple regression analysis identified eGFR to be a variable independently associated only with the log-transformed value of the amount of 24-hr urinary excreted Klotho but not with the log-transformed serum Klotho concentration. Despite the strong correlation between random urine protein-to-creatinine ratio and the 24 hr urinary protein excretion (r = 0.834, p < 0.01), a moderate linear association was observed between the log-transformed value of the amount of 24 hr urinary excreted Klotho and that of the urinary Klotho-to-creatinine ratio (Klotho/Cr) in random urine specimens (r = 0.726, p < 0.01).


The amount of urinary Klotho, rather than the serum Klotho levels, should be linked to the magnitude of the functioning nephrons in CKD patients. The use of random urine Klotho/Cr as a surrogate for the amount of 24-hr urinary excreted Klotho needs to be evaluated more carefully.

Klotho; Chronic kidney disease; Renal function; Urinary protein; Creatinine