Circulating Biologically Active Adrenomedullin Predicts Organ Failure and Mortality in Sepsis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Biologically active adrenomedullin (bio-ADM) is an emerging biomarker for sepsis. We explored whether bio-ADM concentration could predict severity, organ failure, and 30-day mortality in septic patients.

Methods

In 215 septic patients (109 patients with sepsis; 106 patients with septic shock), bio-ADM concentration was measured at diagnosis of sepsis, using sphingotest bio-ADM (Sphingotec GmbH, Hennigsdorf, Germany) and analyzed in terms of sepsis severity, vasopressor use, and 30-day mortality. The number of organ failures, sequential (sepsis-related) organ failure assessment (SOFA) score, and 30-day mortality were compared according to bio-ADM quartiles.

Results

Bio-ADM concentration was significantly higher in patients with septic shock, vasopressor use, and non-survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (all P<0.0001). Bio-ADM quartiles were associated with the number of organ failures ( P<0.0001), as well as SOFA cardiovascular, renal, coagulation, and liver subscores (all P<0.05). The 30-day mortality rate showed a stepwise increase in each bio-ADM quartile (all P<0.0001). Bio-ADM concentration and SOFA score equally predicted the 30-day mortality (area under the curve: 0.827 vs 0.830).

Conclusions

Bio-ADM could serve as a useful and objective biomarker to predict severity, organ failure, and 30-day mortality in septic patients.

Related collections

Most cited references 24

Record: found
Abstract: found
Article: not found

Heart failure and kidney dysfunction: epidemiology, mechanisms and management.

Joerg Schefold, Gerasimos Filippatos, Gerd Hasenfuss … (2016)

Heart failure (HF) is a major health-care problem and the prognosis of affected patients is poor. HF often coexists with a number of comorbidities of which declining renal function is of particular importance. A loss of glomerular filtration rate, as in acute kidney injury (AKI) or chronic kidney disease (CKD), independently predicts mortality and accelerates the overall progression of cardiovascular disease and HF. Importantly, cardiac and renal diseases interact in a complex bidirectional and interdependent manner in both acute and chronic settings. From a pathophysiological perspective, cardiac and renal diseases share a number of common pathways, including inflammatory and direct, cellular immune-mediated mechanisms; stress-mediated and (neuro)hormonal responses; metabolic and nutritional changes including bone and mineral disorder, altered haemodynamic and acid-base or fluid status; and the development of anaemia. In an effort to better understand the important crosstalk between the two organs, classifications such as the cardio-renal syndromes were developed. This classification might lead to a more precise understanding of the complex interdependent pathophysiology of cardiac and renal diseases. In light of exceptionally high mortality associated with coexisting HF and kidney disease, this Review describes important crosstalk between the heart and kidney, with a focus on HF and kidney disease in the acute and chronic settings. Underlying molecular and cellular pathomechanisms in HF, AKI and CKD are discussed in addition to current and future therapeutic approaches.

0 comments Cited 227 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Adrenomedullin in heart failure: pathophysiology and therapeutic application

Adriaan A. Voors, Daan Kremer, Christopher Geven … (2018)

Adrenomedullin (ADM) is a peptide hormone first discovered in 1993 in pheochromocytoma. It is synthesized by endothelial and vascular smooth muscle cells and diffuses freely between blood and interstitium. Excretion of ADM is stimulated by volume overload to maintain endothelial barrier function. Disruption of the ADM system therefore results in vascular leakage and systemic and pulmonary oedema. In addition, ADM inhibits the renin–angiotensin–aldosterone system. ADM is strongly elevated in patients with sepsis and in patients with acute heart failure. Since hallmarks of both conditions are vascular leakage and tissue oedema, we hypothesize that ADM plays a compensatory role and may exert protective properties against fluid overload and tissue congestion. Recently, a new immunoassay that specifically measures the biologically active ADM (bio‐ADM) has been developed, and might become a biomarker for tissue congestion. As a consequence, measurement of bio‐ADM might potentially be used to guide diuretic therapy in patients with heart failure. In addition, ADM might be used to guide treatment of (pulmonary) oedema or even become a target for therapy. Adrecizumab is a humanized, monoclonal, non‐neutralizing ADM‐binding antibody with a half‐life of 15 days. Adrecizumab binds at the N‐terminal epitope of ADM, leaving the C‐terminal side intact to bind to its receptor. Due to its high molecular weight, the antibody adrecizumab cannot cross the endothelial barrier and consequently remains in the circulation. The observation that adrecizumab increases plasma concentrations of ADM indicates that ADM‐binding by adrecizumab is able to drain ADM from the interstitium into the circulation. We therefore hypothesize that administration of adrecizumab improves vascular integrity, leading to improvement of tissue congestion and thereby may improve clinical outcomes in patients with acute decompensated heart failure. A phase II study with adrecizumab in patients with sepsis is ongoing and a phase II study on the effects of adrecizumab in patients with acute decompensated heart failure with elevated ADM is currently in preparation.

0 comments Cited 77 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Plasma adrenomedullin is associated with short-term mortality and vasopressor requirement in patients admitted with sepsis

Rossella Marino, Joachim Struck, Alan Maisel … (2014)

Introduction The incidence of death among patients admitted for severe sepsis or septic shock is high. Adrenomedullin (ADM) plays a central role in initiating the hyperdynamic response during the early stages of sepsis. Pilot studies indicate an association of plasma ADM with the severity of the disease. In the present study we utilized a novel sandwich immunoassay of bioactive plasma ADM in patients hospitalized with sepsis in order to assess the clinical utility. Methods We enrolled 101 consecutive patients admitted to the emergency department with suspected sepsis in this study. Sepsis was defined by fulfillment of at least two systemic inflammatory response syndrome (SIRS) criteria plus clinical suspicion of infection. Plasma samples for ADM measurement were obtained on admission and for the next four days. The 28-day mortality rate was recorded. Results ADM at admission was associated with severity of disease (correlation with Acute Physiology and Chronic Health Evaluation II (APACHE II) score: r = 0.46; P <0.0001). ADM was also associated with 28-day mortality (ADM median (IQR): survivors: 50 (31 to 77) pg/mL; non-survivors: 84 (48 to 232) pg/mL; P <0.001) and was independent from and additive to APACHE II (P = 0.02). Cox regression analysis revealed an additive value of serial measurement of ADM over baseline assessment for prediction of 28-day mortality (P < 0.01). ADM was negatively correlated with mean arterial pressure (r = -0.39; P <0.0001), and it strongly discriminated those patients requiring vasopressor therapy from the others (ADM median (IQR): no vasopressors 48 (32 to 75) pg/mL; with vasopressors 129 (83 to 264) pg/mL, P <0.0001). Conclusions In patients admitted with sepsis, severe sepsis or septic shock plasma ADM is strongly associated with severity of disease, vasopressor requirement and 28-day mortality.

0 comments Cited 55 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Ann Lab Med

Journal ID (iso-abbrev): Ann Lab Med

Journal ID (publisher-id): ALM

Title: Annals of Laboratory Medicine

Publisher: The Korean Society for Laboratory Medicine

ISSN (Print): 2234-3806

ISSN (Electronic): 2234-3814

Publication date (Print): September 2019

Publication date (Electronic): 26 April 2019

Volume: 39

Issue: 5

Pages: 454-463

Affiliations

[1 ]Department of Laboratory Medicine, Konkuk University School of Medicine, Seoul, Korea.

[2 ]Sphingotec GmbH, Hennigsdorf, Germany.

[3 ]Departments of Medical-Surgery Sciences and Translational Medicine, School of Medicine and Psychology, Sapienza – University, Sant' Andrea Hospital, Rome, Italy.

Author notes

Corresponding author: Mina Hur, M.D., Ph.D. Department of Laboratory Medicine, Konkuk University School of Medicine, Konkuk University Medical Center, 120-1 Neungdong-ro, Gwangjin-gu, Seoul 05030, Korea. Tel: +82-2-2030-5581, Fax: +82-2-2636-6764, dearmina@ 123456hanmail.net

Author information

Hanah Kim https://orcid.org/0000-0002-3266-638X

Mina Hur https://orcid.org/0000-0002-4429-9978

Joachim Struck https://orcid.org/0000-0002-9793-7160

Andreas Bergmann https://orcid.org/0000-0002-4466-1682

Salvatore Di Somma https://orcid.org/0000-0002-1717-6585

Article

DOI: 10.3343/alm.2019.39.5.454

PMC ID: 6502946

PubMed ID: 31037864

SO-VID: 302c968b-dd1a-41b2-8fd7-74c140a06b98

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 17 January 2019

Date revision received : 11 March 2019

Date accepted : 19 April 2019

Comments

Comment on this article

scite_

Cited by 21

See all cited by

Most referenced authors 1,132

See all reference authors

Circulating Biologically Active Adrenomedullin Predicts Organ Failure and Mortality in Sepsis

Read this article at

Abstract

Background

Methods

Results

Conclusions

Related collections

Journal of Circulating Biomarkers

Most cited references 24

Heart failure and kidney dysfunction: epidemiology, mechanisms and management.

Adrenomedullin in heart failure: pathophysiology and therapeutic application

Plasma adrenomedullin is associated with short-term mortality and vasopressor requirement in patients admitted with sepsis

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Categories

Comments

Comment on this article

Similar content 196

Cited by 21

Most referenced authors 1,132