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 Carhuapoma; Sanjeev Noel; Roger Johns; Ralph J Fuchs

doi:10.1016/j.jcrc.2017.11.023

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

J Crit Care. 2018 Apr:44:323-330. doi: 10.1016/j.jcrc.2017.11.023. Epub 2017 Nov 16.

Authors

Peter A Abdelmalik¹, Robert D Stevens², Sarabdeep Singh³, John Skinner³, J Ricardo Carhuapoma⁴, Sanjeev Noel⁵, Roger Johns³, Ralph J Fuchs⁶

Affiliations

¹ Department of Neurology, State University of New York, University at Buffalo, Buffalo, NY 14202, United States. Electronic address: peterabd@buffalo.edu.
² Department of Anesthesia and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Radiology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
³ Department of Anesthesia and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
⁴ Department of Anesthesia and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States; Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
⁵ Division of Nephrology, Department of Medicine, The Johns Hopkins University, Baltimore, MD 21287, United States.
⁶ Department of Anaesthesiology, The University of Auckland, Grafton, Auckland, New Zealand; Hauora Tairāwhiti District Health Board, Gisborne 4040, New Zealand.

PMID: 29268200
DOI: 10.1016/j.jcrc.2017.11.023

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 72h 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.

Keywords: Acute physiology; Biomarker; Frailty; Longevity; Resilience; Senescence; Sepsis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Biomarkers / blood
Female
Glucuronidase / blood*
Hospital Mortality
Humans
Intensive Care Units
Klotho Proteins
Male
Middle Aged
Predictive Value of Tests
Prognosis
Prospective Studies
Shock, Septic / blood*
Shock, Septic / mortality
Stress, Physiological / physiology*

Substances

Biomarkers
Glucuronidase
Klotho Proteins