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Serum levels of soluble secreted α-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis

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Abstract

Background

α-Klotho was first identified as an aging gene and was later shown to be a regulator of phosphate metabolism. Fibroblast growth factor 23 (FGF23) is the key regulator of phosphate metabolism. Serum levels of soluble α-Klotho in chronic kidney disease (CKD) patients have not previously been determined, especially in relation with FGF23 and creatinine levels. This study was designed to investigate whether serum soluble α-Klotho levels are modulated by renal function, age, and FGF23 level in CKD patients. This study is the first report on the utility of measuring soluble α-Klotho levels in human CKD.

Methods

A total of 292 CKD patients were enrolled. Serum samples were collected, and FGF23 and soluble α-Klotho levels were measured using enzyme-linked immunosorbent assay kits. In addition, serum creatinine, hemoglobin, albumin, calcium, and phosphate levels were measured.

Results

Serum soluble α-Klotho levels were associated positively with estimated glomerular filtration rate (eGFR) (P < 0.0001) and inversely with serum creatinine level (P < 0.01). Interestingly, α-Klotho levels were significantly decreased in stage 2 CKD compared with stage 1 (P = 0.0001). Serum FGF23 levels were associated positively with serum creatinine and negatively with eGFR. FGF23 levels were significantly increased in stage 5 compared with stage 1 CKD. Soluble α-Klotho was associated inversely with log-transformed FGF23 level (P < 0.01).

Conclusion

Our data indicate that soluble α-Klotho levels are significantly decreased in stage 2 CKD compared to stage 1, and not only in the advanced stages of the disease. Soluble α-Klotho may thus represent a new biomarker for the diagnosis of CKD, especially in the early stage.

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Acknowledgments

This work was supported by Daiwa Memorial foundation, Japanese Kidney foundation, and a grant from the Ministry of Education, Science, Culture and Sports of Japan (to Y. S., K. I., K. O., S. F., and Y. T.) and a grant of Kochi Organization for Medical Reformation and Renewal to Y.T. We thank Ms. Reiko Matumoto, Ms. Sekie Saito for technical assistances.

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Authors and Affiliations

  1. Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Kohashu, Oko-cho, Nankoku, 783-8505, Japan

    Yoshiko Shimamura, Kazu Hamada, Kosuke Inoue, Koji Ogata, Masayuki Ishihara, Toru Kagawa, Mari Inoue, Shimpei Fujimoto & Yoshio Terada

  2. Laboratory Medicine, Kochi Medical School, Kochi University, Kohashu, Oko-cho, Nankoku, 783-8505, Japan

    Shigeo Yamanaka & Teturo Sugiura

  3. Kochi-Takasu Hospital, Kochi, Japan

    Mika Ikebe & Kenji Yuasa

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  1. Yoshiko Shimamura
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  2. Kazu Hamada
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Correspondence to Yoshio Terada.

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Shimamura, Y., Hamada, K., Inoue, K. et al. Serum levels of soluble secreted α-Klotho are decreased in the early stages of chronic kidney disease, making it a probable novel biomarker for early diagnosis. Clin Exp Nephrol 16, 722–729 (2012). https://doi.org/10.1007/s10157-012-0621-7

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  • DOI: https://doi.org/10.1007/s10157-012-0621-7

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