Clinical Significance of Serum Soluble Klotho Levels in Sepsis-Associated Encephalopathy: A Single-Center Prospective, Preliminary Study

Background/Objectives: Sepsis-associated encephalopathy (SAE) is an acute brain dysfunction during sepsis with high mortality. Klotho protein is notable for its identified neuroprotective effects in chronic neurodegenerative diseases. This study evaluated temporal changes in serum soluble Klotho levels and their association with clinical recovery in SAE. Methods: In this prospective observational study, 750 intensive care unit (ICU) patients were screened and 42 patients with SAE were included. Serum soluble Klotho levels, inflammatory markers, and Glasgow Coma Scale (GCS) scores were recorded on days 1 and 3. Associations between changes in Klotho levels and clinical and inflammatory parameters were analyzed. Results: The median GCS score increased from 11 (IQR: 10–13) on day 1 to 12 (IQR: 10–13) on day 3 (p < 0.001). Serum soluble Klotho levels decreased significantly from 8114.5 ± 3515.7 pg/mL on day 1 to 6452.9 ± 3390 pg/mL on day 3 (p < 0.001). Inflammatory markers, including C-reactive protein and procalcitonin, also showed significant reductions over time (p < 0.001). A moderate negative correlation was observed between changes in Klotho levels and GCS scores (r = −0.56, p < 0.001). Changes in inflammatory markers were not significantly correlated with Klotho dynamics. Conclusions: Serum soluble Klotho levels decrease in parallel with neurological improvements in sepsis-associated encephalopathy and are significantly associated with changes in GCS scores. These findings suggest that Klotho may represent a potential biomarker of disease trajectory and neurological recovery.