Association between α-klotho and frailty progression at dialysis initiation: a prospective cohort study

Frailty progression is a common issue among patients with end-stage renal disease receiving dialysis, profoundly affecting their prognosis and quality of life. α-klotho is an anti-aging protein that might contribute to frailty progression. We aimed to determine whether α-klotho levels at dialysis initiation are associated with subsequent frailty progression. We conducted a prospective cohort study of 65 patients with end-stage renal disease who were newly started on hemodialysis. Frailty progression was defined as an increase of ≥ 1 point in the clinical frailty scale from baseline to 3 months. In the primary analysis, serum soluble α-klotho was modeled linearly per 100 pg/mL increase. After multiple imputation, multivariable modified Poisson regression analysis was performed adjusting for age, sex, emergency dialysis initiation, baseline clinical frailty scale, diabetes mellitus, short physical performance battery, and C-reactive protein. A parsimonious sensitivity analysis was performed adjusting for age, sex, and emergency dialysis initiation to assess the robustness of the findings against potential overfitting. In the primary linear model, each 100 pg/mL increase in serum soluble α-klotho was associated with a lower risk of frailty progression over 3 months after dialysis initiation (risk ratio [RR], 0.80; 95% confidence interval [CI], 0.66–0.97; p = 0.021). The association remained statistically significant in the parsimonious sensitivity analysis (RR, 0.79; 95% CI, 0.66–0.95; p = 0.014). In the primary linear model, higher baseline serum soluble α-klotho levels were associated with a lower average risk of 3-month frailty progression after dialysis initiation. Exploratory analysis suggested possible nonlinearity; therefore, these findings require cautious interpretation given the modest sample size, single-center design, and nonsignificant association with SPPB decline.