Mid-Regional Pro-Adrenomedullin Can Predict Organ Failure and Prognosis in Sepsis?

Abstract

Sepsis causes immune dysregulation and endotheliitis, with an increase in mid-regional pro-adrenomedullin (MR-proADM). The aim of the study is to determine an MR-proADM value that, in addition to clinical diagnosis, can identify patients with localized infection or those with sepsis/septic shock, with specific organ damage or with the need for intensive care unit (ICU) transfer and prognosis. The secondary aim is to correlate the MR-proADM value with the length of stay (LOS). In total, 301 subjects with sepsis (124/301 with septic shock) and 126 with localized infection were retrospectively included. In sepsis, MR-proADM ≥ 3.39 ng/mL identified acute kidney injury (AKI); ≥2.99 ng/mL acute respiratory distress syndrome (ARDS); ≥2.28 ng/mL acute heart failure (AHF); ≥2.55 ng/mL Glascow Coma Scale (GCS) < 15; ≥3.38 multi-organ involvement; ≥3.33 need for ICU transfer; ≥2.0 Sequential Organ Failure Assessment (SOFA) score ≥ 2; and ≥3.15 ng/mL non-survivors. The multivariate analysis showed that MR-proADM ≥ 2 ng/mL correlates with AKI, anemia and SOFA score ≥ 2, and MR-proADM ≥ 3 ng/mL correlates with AKI, GCS < 15 and SOFA score ≥ 2. A correlation between mortality and AKI, GCS < 15, ICU transfer and cathecolamine administration was found. In localized infection, MR-proADM at admission ≥ 1.44 ng/mL identified patients with AKI; ≥1.0 ng/mL with AHF; and ≥1.44 ng/mL with anemia and SOFA score ≥ 2. In the multivariate analysis, MR-proADM ≥ 1.44 ng/mL correlated with AKI, anemia, SOFA score ≥ 2 and AHF. MR-proADM is a marker of oxidative stress due to an infection, reflecting severity proportionally to organ damage.

A Focus on the Pathophysiology of Adrenomedullin Expression: Endothelitis and Organ Damage in Severe Viral and Bacterial Infections

“…This evidence underscores the crucial functions of ADM and the importance of information on the degree of endothelitis and dysregulation of the ADM system provided by the ADM and/or MR-proADM assay [ 4 , 120 , 121 , 122 , 123 ]. Indeed, the value of MR-proADM, which correlates directly with the extent of organ damage, indicates organ dysfunction, disease severity, diagnosis and prognosis in patients with severe viral and bacterial infections [ 4 , 120 , 121 , 122 , 123 ].…”

“…Furthermore, MR-proADM acts as a biomarker for sepsis, reflecting the degree of oxidative stress and indicating the severity of the condition in line with organ damage and prognosis [ 120 , 124 ]. From a clinical perspective, MR-pro-ADM can accurately detect patients with one or multiple organ failures, particularly showing a stronger correlation for certain variables such as acute kidney injury (AKI), GCS < 15, and the requirement for intensive care unit (ICU) transfer indicating a more severe prognosis [ 19 , 20 , 120 , 125 , 126 , 127 , 128 , 129 ].…”

“…In a recent study, it was found that the designated threshold level of MR-proADM (which achieved the optimal balance between sensitivity and specificity) for detecting patients with localized infection was 1.44 ng/mL. For identifying patients with sepsis with a SOFA score greater than 2, as well as distinguishing those needing ICU transfer or unlikely to survive beyond 90 days, the threshold value proved to be 2 ng/mL [ 120 ].…”

“…Severe viral or bacterial infections cause inflammation with increment of C-reactive protein (CRP) and neopterin and oxidative stress with increased production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) and subsequent increment of NOx levels [ 22 , 23 , 45 , 133 ]. This results in direct damage to ECs (endothelitis with an increase of ADM expression), of the junctional proteins (Jps) between ECs and of the glycocalyx of ECs, resulting in impairment of the ACE2 and ADM systems, and of the Angiopoietin/Tie (Ang/Tie) axis [ 45 , 120 , 132 , 133 ].…”

REG1A may be a new biological marker for diagnosing sepsis

“…A new study reported that we identi ed a dynamically changing haematological-immunological pro le of sepsis, including lymphopenia, reduced dendritic cell frequency and myeloid HLA-DR expression, even though C-reactive protein, a common clinical marker of in ammation, is not elevated, which is characteristic of sepsis [8]. Mid-region adrenomedullinogen (MR-proADM) is a marker of infection-induced oxidative stress, re ecting severity proportional to organ damage [9].Elevated C-reactive protein to albumin ratio (CAR) is associated with increased mortality and poor prognosis in patients with sepsis [10]. The neutrophil index (DNI) has shown better validity in differentiating septic febrile patients from non-septic febrile patients [11].…”