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

Peter A. Abdelmalik, Robert D. Stevens, Sarabdeep Singh, John Skinner, J. Ricardo Carhuaopoma, Sanjeev Noel, Roger Johns, Ralph J. Fuchs

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)323-330
Number of pages8
JournalJournal of Critical Care
Volume44
DOIs
StatePublished - Apr 2018

Keywords

  • Acute physiology
  • Biomarker
  • Frailty
  • Longevity
  • Resilience
  • Senescence
  • Sepsis

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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