CRITICAL ILLNESS METABOLOMICS REGARDING INFLAMMATION AND KIDNEY DYSFUNCTION: POST-HOC ANALYSES OF THE VITDAL-ICU TRIAL

Abstract

OVERVIEW: During the Master of Medical Sciences program at Harvard Medical School, I have focused on the metabolomics of critical illness. Critical illness is a life-threatening condition and presents high hospital mortality as much as 20% to 40%. One in five Americans dies due to critical illness. Despite specialized care in the intensive care unit (ICU), there are few specific treatments to treat critically ill patients effectively. The reason for this is supposed that the heterogeneity of patients with critical illness. Metabolomics research is the large-scale, exhaustive analysis of metabolites that may reflect many reactions influenced by environments and diseases in human body. Metabolomic research is supposed to be able to subdivide heterogeneous patient groups into patient’s subtypes according to metabolomic profiles. Manuscript 1: Acute inflammation is an early nonspecific response to cell stress and injury that is common in almost of critical illness. Recent metabolomic research has not addressed the metabolic response to acute inflammation in general critically ill patients. We hypothesized that there is a specific plasma metabolomic profile that represents a response to elevated procalcitonin in critical illness. Manuscript 2: Acute renal failure is a major organ failure in critically ill patients. Previous metabolomic investigations among specific patient groups revealed some metabolites were associated with acute kidney injury. However, a metabolomic profile related to acute kidney dysfunction in general critically ill patients remains unclear. We hypothesized a specific plasma metabolomic profile is different according to the acute changes of serum creatinine levels in nonspecific patients with critical illness.