Anti-aging factor, serum alpha-Klotho, as a marker of acute physiological stress, and a predictor of ICU mortality, in patients with septic shock

Purpose: Genetic deletions decreasing serum alpha-Klotho (alpha-KL) have been associated with rapid aging, multi-organ failure and increased mortality in experimental sepsis. We hypothesized that lower alpha-KL obtained at the onset of septic shock correlates with higher mortality. Materials and methods: Prospective cohort of 104 adult patients with septic shock. Alpha-KL was measured via ELISA on serum collected on the day of enrollment (within 72 h from the onset of shock). Relationship between alpha-KL and clinical outcome measures was evaluated in uni- and multi-variable models. Results: Median (IQR) alpha-KL was 816 (1020.4) pg/mL and demonstrated a bimodal distribution with two distinct populations, Cohort A [n = 97, median alpha-KL 789.3 (767.1)] and Cohort B [n = 7, median alpha-KL 4365.1(1374.4), > 1.5 IQR greater than Cohort A]. Within Cohort A, ICU non-survivors had significantly higher serum alpha-KL compared to survivors as well as significantly higher APACHE II and SOFA scores, rates of mechanical ventilation, and serum BUN, creatinine, calcium, phosphorus and lactate (all p ≤ 0.05). Serum alpha-KL ≥ 1005, the highest tertile, was an independent predictor of ICU mortality when controlling for co-variates (p = 0.028, 95% CI 1.143–11.136). Conclusions: Elevated serum alpha-KL in patients with septic shock is independently associated with higher mortality. Further studies are needed to corroborate these findings.