Abstract
Adrenomedullin (ADM) is a peptide with pleiotropic effects in systemic inflammation. Its more stable precursor protein midregional proadrenomedullin (MRproADM) can be measured more reliably compared to ADM. Our objective was to investigate the potential role of MRproADM as a diagnostic and prognostic biomarker in critically ill patients at the intensive care unit (ICU). We therefore measured MRproADM in 203 ICU patients and 66 healthy controls. We found that MRproADM levels are significantly increased in critically ill patients as compared to healthy controls. MRproADM levels are significantly increased in patients with sepsis, but its diagnostic value for identifying sepsis is numerically lower than that of established markers (e.g., interleukin-6, C-reactive protein, and procalcitonin). MRproADM levels are closely correlated to endothelial and organ dysfunction, inflammation, and established clinical scores (APACHE II, SOFA, and SAPS2). MRproADM concentrations correlate with vasopressor use but not fluid balance. Increased MRproADM levels (cut − off > 1.4 nmol/L) in critically ill patients are independent predictors of ICU and overall mortality during a follow-up of up to 26 months (OR 3.15 for ICU mortality, 95% CI 1.08-9.20, p = 0.036; OR for overall mortality 2.4, 95% CI 1.12-5.34, p = 0.026). Our study demonstrates the potential of MRproADM serum levels as a prognostic biomarker in critical illness for ICU mortality and long-term survival during follow-up.
Highlights
Adrenomedullin (ADM) is a 52-amino-acid peptide first discovered in 1993 in pheochromocytoma cells [1]
In 136 patients, sepsis and septic shock were the major causes of intensive care unit (ICU) admission
For ICU mortality, we could demonstrate that the AUC of MRproADM (0.670; 95% 95% confidence interval (CI) 0.556-0.785) is lower than the widely used acute physiology and chronic health evaluation score (APACHE) acute physiology and chronic health evaluation (II) score (0.701; 95% CI 0.577-0.825) and higher than procalcitonin (0.574; 95% CI 0.463-0.686)
Summary
Adrenomedullin (ADM) is a 52-amino-acid peptide first discovered in 1993 in pheochromocytoma cells [1]. It is expressed in various tissues (e.g., adrenal medulla, pancreas, heart, aorta, kidneys, lungs, and macrophages) [2] and has pleiotropic biological effects, including vasodilation, inotropy, immune modulation, and diuretic effects, especially in the presence of proinflammatory stimuli [3, 4]. The vasodilatory properties of ADM are of special interest in the pathophysiology of sepsis. A nonfunctional fragment of its precursor protein, midregional fragment of proadrenomedullin (MRproADM) is larger and more stable than active ADM [9]. MRproADM measurements can be used as reliable surrogates in predicting biological effects of ADM [10]
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