Higher α-Klotho Levels Linked to Lower Frailty Progression After Dialysis initiation: Study

A new study published in the journal of BMC Nephrology revealed that higher baseline serum soluble α-klotho levels were associated with a lower average risk of frailty progression within 3 months after dialysis initiation. Exploratory findings suggested a possible nonlinear relationship. However, the results should be interpreted cautiously because of the small sample size, single-center design, and lack of a significant association with SPPB decline.

This research followed 65 patients with end-stage renal disease (ESRD) who had recently initiated hemodialysis to investigate whether baseline serum soluble α-klotho levels were associated with subsequent frailty progression. Frailty was assessed using the Clinical Frailty Scale (CFS), with progression defined as an increase of at least one point between the start of dialysis and the 3-month follow-up.

The study found that patients with higher circulating α-klotho levels experienced a significantly lower risk of frailty progression. In the primary analysis, every 100 pg/mL increase in serum soluble α-klotho was associated with a 20% reduction in the risk of worsening frailty over the three-month period. After adjusting for potential confounding factors, the association remained statistically significant.

A simplified sensitivity analysis found the protective association persisted, with each 100 pg/mL increase in α-klotho linked to a 21% lower risk of frailty progression, reinforcing the robustness of the primary findings.

α-Klotho is widely recognized as an anti-aging protein involved in regulating mineral metabolism, reducing oxidative stress, and protecting against tissue damage. Previous studies have linked reduced α-klotho levels to kidney disease progression and age-related disorders. The new findings add to growing evidence that α-klotho may also play an important role in maintaining physical resilience during the early stages of dialysis treatment.

Exploratory analyses suggested the relationship between α-klotho levels and frailty progression may not be strictly linear, indicating that additional research is needed to clarify the nature of the association. Furthermore, the study involved a relatively small sample from a single medical center, limiting the generalizability of the results. The investigators also found no statistically significant association between α-klotho levels and declines in the Short Physical Performance Battery (SPPB), another measure of physical function.

Overall, higher baseline serum soluble α-klotho levels are associated with a lower average risk of frailty progression during the first three months after starting hemodialysis. They recommend that larger, multicenter studies be conducted to validate these findings and explore whether α-klotho could serve as a useful biomarker or therapeutic target for preserving physical function and improving outcomes in patients beginning dialysis.

Reference:

Hirano, Y., Fujikura, T., Yamaguchi, T., Kono, K., Kato, A., Ohashi, N., Omura, T., Nagafusa, T., Yamauchi, K., & Yasuda, H. (2026). Association between α-klotho and frailty progression at dialysis initiation: a prospective cohort study. BMC Nephrology. https://doi.org/10.1186/s12882-026-05319-9