Soluble Klotho Is Associated with Body Weight Loss in Patients Undergoing Hemodialysis

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Abstract Title *

Soluble Klotho Is Associated with Body Weight Loss in Patients Undergoing Hemodialysis

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Co-author 1

Akio Nakashima a-nakashima@jikei.ac.jp The Jikei University School of Medicine Department of Internal Medicine Tokyo Japan *

Co-author 2

Yuriko Shibata fukudayu1993@gmail.com The Jikei University School of Medicine Department of Internal Medicine Tokyo Japan -

Co-author 3

Kazuhiko Kato kazu.j429@gmail.com The Jikei University School of Medicine Department of Internal Medicine Tokyo Japan -

Co-author 4

Arisa Kobayashi arisa.kobayashi07@gmail.com The Jikei University School of Medicine Department of Internal Medicine Tokyo Japan -

Co-author 5

Ichiro Ohkido iohkido@jikei.ac.jp The Jikei University School of Medicine Department of Internal Medicine Tokyo Japan -

Co-author 6

Takashi Yokoo tyokoo@jikei.ac.jp The Jikei University School of Medicine Department of Internal Medicine Tokyo Japan -

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Introduction

Soluble Klotho (sKlotho), an anti-aging protein primarily produced by the kidney, regulates mineral metabolism and energy balance. Experimental data indicate that Klotho deficiency causes weight loss and renal cachexia; however, its clinical relevance in patients undergoing hemodialysis remains uncertain.

Methods

This retrospective observational study followed patients undergoing maintenance hemodialysis for 36 months. Baseline serum sKlotho concentrations were measured using ELISA. The primary outcome was the change in dry body weight. Associations between sKlotho and weight change were analyzed using multivariable linear regression adjusted for age, sex, dialysis vintage, and mineral metabolism parameters.

Results

Among 664 participants (mean age = 65.1 ± 11.3 years; 66.2% male), baseline sKlotho levels were 314.1 pg/mL (interquartile range, 246.2–413.4). Patients with lower sKlotho levels experienced greater body weight loss during 36 months than those with higher levels after adjustment (β = 0.08 [95% confidence interval, 0.01–0.14; P = 0.021]). No significant correlation was found between sKlotho and serum creatinine. Subgroup analyses stratified by age, calcium, phosphorus, FGF23, and 25OHD yielded consistent results, with no significant interaction.

Conclusion

Lower circulating sKlotho levels were independently associated with subsequent body weight loss in patients undergoing hemodialysis. These findings suggest that Klotho deficiency may contribute to renal cachexia through adipose tissue depletion. Further research is needed to clarify Klotho’s role in energy metabolism and to evaluate potential Klotho-based therapies.

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