Cathelicidin antimicrobial protein, vitamin D, and risk of death in critically ill patients

David E Leaf, Heather E Croy, Sara J Abrahams, Anas Raed, Sushrut S Waikar

Decreased production of cathelicidin antimicrobial protein-18 (hCAP18) has been proposed to be a key mechanism linking decreased 25-hydroxyvitamin D (25D) levels with adverse outcomes among critically ill patients. However, few studies in humans have directly assessed plasma hCAP18 levels, and no study has evaluated the association between hCAP18 levels and adverse outcomes among critically ill patients. We performed a single-center, prospective cohort study among 121 critically ill patients admitted to intensive care units (ICUs) between 2008 and 2012. We measured plasma hCAP18, 25D, D-binding protein, and parathyroid hormone levels on ICU day 1. The primary endpoint was 90-day mortality. Secondary endpoints included hospital mortality, sepsis, acute kidney injury, duration of mechanical ventilation, and hospital length of stay. ICU day 1 hCAP18 levels were directly correlated with 25D levels (Spearman's rho (rs) = 0.30, P = 0.001). In multivariate analyses adjusted for age and Acute Physiology and Chronic Health Evaluation II (APACHE II) score, patients with hCAP18 levels in the lowest compared to highest tertile on ICU day 1 had a 4.49 (1.08 to 18.67) greater odds of 90-day mortality, and also had greater odds of sepsis. ICU day 1 levels of other analytes were not associated with 90-day mortality. Lower 25D levels on ICU day 1 are associated with lower hCAP18 levels, which are in turn associated with a greater risk of 90-day mortality. These findings provide a potential mechanistic basis for the frequently observed association between low 25D levels and poor outcomes in critically ill patients.