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Chronic kidney disease (CKD) is recognized as a state of accelerated aging, characterized not only by impaired renal function but also by sarcopenia, functional decline and vascular dysfunction. In patients undergoing maintenance hemodialysis, reduced physical activity is associated with poorer prognosis and decreased quality of life. Therefore, the importance of renal rehabilitation centered on exercise therapy has gained increasing attention.

α-Klotho—known as an anti-ageing hormone—is attracting attention. α-Klotho is predominantly expressed in the distal renal tubules and regulates phosphate metabolism, oxidative stress, and endothelial function. Reduced serum α-Klotho levels are associated with CKD progression, cardiovascular disease, and mortality. α-Klotho is being actively investigated as a promising biomarker candidate in kidney disease research.

A research group led by Professor Misa Miura, Faculty of Health Sciences, Tsukuba University of Technology, investigated the association between habitual physical activity and serum α-Klotho levels in hemodialysis patients and, furthermore, the potential application to renal rehabilitation through exercise intervention cases.

【Research Overview】
The study was conducted using a combination of case studies to examine the effects of exercise intervention in individual cases, and cross-sectional study investigating the association between habitual physical activity and serum α-Klotho levels.
- Cross-sectional study: 24 undergoing maintenance hemodialysis patients and 18 healthy controls.
- Serum α-Klotho levels were measured using ELISA.
- Habitual physical activity was assessed by structured interviews. Exercise intensity was quantified by MET values.
- High-intensity interval training (HIIT) was administered to one male patient in his 60s undergoing maintenance hemodialysis for more than 10 years, and the effects were prospectively evaluated.

【Key Findings】
- Significantly lower serum α-Klotho levels in hemodialysis patients than in healthy controls (p < 0.001) .
- A moderate positive correlation between habitual physical activity and serum α-Klotho levels in hemodialysis patients (r = 0.52, p = 0.02).
- Hemodialysis patients with habitual physical activity levels ≥3 METs showed significantly higher serum α-Klotho levels than those with activity levels <3 METs (p = 0.001).
- In the HIIT case, the Barthel Index (BI) score improved from 90 to 100, and the SPPB score increased from 10 to 12. Peak exercise intensity rose from 2.0 to 5.5 METs.
- Exercise program was completed without any adverse events, such as intradialytic hypotension or excessive fatigue.

【Potential of α-Klotho, demonstrated by the study】
The most significant insight is the association between habitual physical activity and serum α-Klotho levels in hemodialysis patients. Physical function decline associated with aging and reduced renal function is a major concern for dialysis patients. These findings suggest that α-Klotho may be a molecular biomarker reflecting physical function and activity levels.

Furthermore, the authors integrated findings from both the HIIT case study and the cross-sectional study, suggesting that molecular biomarkers such as α-Klotho may complement conventional functional assessments in renal rehabilitation. While renal rehabilitation has traditionally focused on functional outcomes such as walking ability and activities of daily living (ADL), the incorporation of molecular markers may provide a more multifaceted approach to patient evaluation.

This study provides clinically meaningful evidence that serum α-Klotho, known as an anti-ageing factor, may be associated with physical activity and functional status in hemodialysis patients. Further large-scale prospective studies and exercise intervention studies are expected to clarify the potential role of α-Klotho as a useful biomarker in renal rehabilitation and dialysis care.

Please refer to the following publication for more details.

Misa Miura et al.
Association Between Serum α-Klotho Levels and Habitual Physical Activity in Hemodialysis Patients: A Pilot Clinical Study
J Clin Med. 2026 Jun 4;15(11):4341.


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