Bio-Adrenomedullin and Dipeptidyl Peptidase 3 as Novel Sepsis Biomarkers in the Emergency Department and the Intensive Care Unit: A Narrative Review

Figures

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  Figure 1. The role of bio-ADM in vascular homeostasis and its clinical utility in patients presenting to the ED or the ICU with sepsis. After being released in circulation, bio-ADM displays diverse effects on the vasculature. Bio-ADM binds to its receptors located on the vascular endothelium and results in decreased vascular permeability by promoting the stability of the EB (green arrows), thereby limiting fluid shift towards the extravascular compartment. In parallel, however, bio-ADM moves into the interstitium where it induces relaxation through binding to its receptors located on the VSMCs (red arrows), thereby causing vasodilation and deterioration of systemic hemodynamics [5,10,11,19]. As a biomarker, bio-ADM has been shown to be potentially useful as a diagnostic tool for sepsis [41,42], as a marker of sepsis severity, morbidity and early risk stratification [12,20,26,42,43,44,45,46], as a prognosticator of mortality [12,20,26,41,42,43,44,45,46], and as a tool for treatment monitoring and guidance [26,43]. Abbreviations: Bio-ADM = bioactive adrenomedullin; EB = endothelial barrier; ED = emergency department; ICU = intensive care unit; t1/2 = half-life; LOS = length of stay; MOF =…

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  Figure 2. The role of DPP3 in hemodynamics and its clinical utility in patients presenting to the ED or the ICU with sepsis. Presumably, after cellular lysis, the cytosolic enzyme DDP3 is released into the circulation, whereby it antagonizes the renin–angiotensin–aldosterone system by cleaving Ang II. As a result of enhanced Ang II degradation by DPP3, all events occurring downstream of Ang II synthesis are inhibited, thereby blunting vasoconstriction of VSMCs and inducing vasodilation. By doing so, DPP3 exerts a negative impact on the hemodynamics of patients with sepsis and/or septic shock [5,48,56,61]. Current literature supports the role of DDP3 in risk stratification of septic patients, in the prediction of sepsis morbidity and mortality [51,58,62,63,64], and in treatment guidance of sepsis and/or septic shock [58,62,63]. Abbreviations: AKI = acute kidney injury; Ang II = angiotensin II; DPP3 = dipeptidyl peptidase 3; ED = emergency department; ICU = intensive care unit; t1/2 = half-life; LOS = length of stay; MOF = multiple organ failure; MV = mechanical ventilation; RRT = renal replacement therapy; VSMC: vascular smooth muscle cell.