Serum Klotho as a potential biomarker for prognosis in acute ischemic stroke.

<h4>Objective</h4>To investigate the association between serum Klotho levels and 90-day functional outcome in patients with acute ischemic stroke (AIS), and to assess its potential as a short-term prognostic biomarker.<h4>Methods</h4>This single-center retrospective observational cohort study included 200 patients with AIS. Patients were divided into favorable outcome group [90-day modified Rankin Scale (mRS) 0-2, <i>n</i> = 140] and unfavorable outcome group (mRS 3-6, <i>n</i> = 60). Unfavorable 90-day outcome was used as the binary dependent variable. Baseline characteristics were compared between groups. Univariate and multivariable logistic regression analyses were performed to assess the association between serum Klotho and unfavorable outcome. Klotho levels were also analyzed by quartiles with trend testing. Restricted cubic spline analysis was used to evaluate the dose-response pattern. Receiver operating characteristic curves and the DeLong test were used to compare the predictive performance of the Klotho-alone, clinical, and combined models. Sensitivity analyses were conducted to assess robustness.<h4>Results</h4>Serum Klotho levels were significantly lower in patients with unfavorable outcomes than in those with favorable outcomes [579.65 (444.50, 664.12) pg/mL vs. 754.05 (656.00, 817.95) pg/mL, <i>p</i> < 0.001]. After adjustment for age, sex, baseline NIHSS score, atrial fibrillation, diabetes, eGFR, hsCRP, time from symptom onset to blood collection, and reperfusion therapy, each 1-standard deviation increase in serum Klotho was associated with a lower risk of unfavorable outcome (<i>OR</i> = 0.294, 95% <i>CI</i>: 0.158-0.505, <i>p</i> < 0.001). Compared with the lowest quartile, higher Klotho quartiles were associated with reduced risk, with a significant trend across quartiles (<i>p</i> < 0.001). Restricted cubic spline analysis showed a significant overall association but no significant nonlinear relationship. The AUCs of the Klotho-alone, clinical, and combined models were 0.836, 0.868, and 0.902, respectively, although the improvement over the clinical model was not statistically significant. Sensitivity analyses showed consistent results.<h4>Conclusion</h4>Lower early serum Klotho levels were independently associated with unfavorable 90-day outcome in patients with AIS. However, its incremental predictive value beyond established clinical variables was not statistically confirmed. Further prospective studies are needed to validate its prognostic utility.