New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ failure

Abstract

Mid-regional pro-adrenomedullin (MR-proADM) has a good biomarker profile: its half-life is several hours, and its plasma concentrations can be determined in clinical practice, it is essentially irrelevant, but proportionally represents the levels and activity of adrenomedullin (ADM). ADM synthesis is widely distributed in tissues, including bone, adrenal cortex, kidney, lung, blood vessels and heart. Its fundamental biological effects include vasodilator, positive inotropic, diuretic, natriuretic and bronchodilator. It has been described high levels in septic patients, interacting directly with the relaxation of vascular tone, triggering hypotension of these patients. It is also found high levels in other diseases such as hypertension, heart failure, respiratory failure, renal failure, cirrhosis and cancer. MR-proADM has been identified as a prognostic marker, stratifying the mortality risk in patients with sepsis in emergency department (ED) and ICU. Evolutionary MR-proADM levels and clearance marker to the 2nd-5th days of admission help to determine the poor performance and the risk of mortality in patients with severe sepsis admitted to the ICU. The MR-proADM levels are more effective than procalcitonin (PCT) and C-reactive protein (CRP) levels to determine an unfavorable outcome and the risk of mortality in patients with sepsis admitted to the ICU. It has also proved useful in patients diagnosed with organ dysfunction of infectious etiology. MR-proADM levels are independent of the germ conversely it is related to the magnitude of organ failure and therefore severity. We consider advisable incorporating the MR-proADM the panel of biomarkers necessary for the diagnosis and treatment of critically ill patients admitted to the ICU with severe sepsis. The combined PCT and MR-proADM levels could represent a valid tool in the clinical practice to timely identify patients with bacterial infections and guide the diagnosis and treatment of sepsis and septic shock.

Adrenomedullin surges are linked to acute episodes of the systemic capillary leak syndrome (Clarkson disease)

“…11 To overcome this hurdle, we measured levels of pro-ADM, a biologically inactive yet chemically stable mid-region precursor of ADM that is released together with ADM at a 1:1 ratio; has a half-life of several hours; and has been used as a surrogate for ADM in other diseases. 12,13 Serum pro-ADM levels were significantly elevated in acute SCLS sera compared to either convalescent SCLS sera or sera from healthy controls (Figure 3A). There appeared to be two distinct groups: one with relatively high pro-ADM levels during the acute phase, and another with significantly lower values ( p <0.0001, Mann-Whitney).…”

Novel heart failure biomarkers: why do we fail to exploit their potential?

“…ADM is produced as a precursor protein called preproadrenomedullin in numerous tissues including adrenal glands, endothelium, vascular smooth muscles, renal parenchyma, and cardiomyocytes. This protein undergoes complex processing, first generating pro-ADM, which subsequently is cleaved into multiple peptides including mid-regional proADM (MR-proADM) and ADM; the latter can exist in both a bioactive amidated form (bio-ADM) and a glycated inactive form [140]. Whether MR-proADM has biological activity is unclear, but because it is more stable than ADM, it is the preferred biomarker.…”

“…Whether MR-proADM has biological activity is unclear, but because it is more stable than ADM, it is the preferred biomarker. Like PCT, MRproADM is strongly elevated in sepsis and could be used as a prognostic marker and to guide the diagnosis and treatment of sepsis [140]. MR-proADM lacks specificity for the diagnosis of HF, but the BACH study demonstrated that MR-proADM had superior accuracy for predicting 90-day mortality compared with BNP in acute HF [141].…”

Copeptin, myeloperoxidase and pro-adrenomedullin for acute coronary syndrome in patients with chronic kidney disease

“…Pro-ADM, with a half-life of a few hours, peaks between 24 to 48 hours after onset of symptoms of myocardial infarction. [60][61][62] While it has not been shown to have utility in the early diagnosis of myocardial infarction, it may be prognostic of adverse outcomes and all-cause mortality among patients presenting with acute chest pain. 31,63 Elevated levels are seen in other cardiovascular conditions, including congestive heart failure 64,65 and hypertension, 66 as well as noncardiovascular conditions such as systemic inflammatory states 67 and type 2 diabetes mellitus.…”