Role of Mitochondrial Dysfunction in the Occurrence of Acute Kidney Injury (AKI) in Postoperative Cardiac Surgery

2019-10-18 11:21:42 | BioPortfolio


Cardiac Surgery and Acute Kidney Failure (AKI) post Surgery:

AKI is a frequent complication in the immediate aftermath of cardiac surgery with an incidence varying from 5 to 40%. KDIGO criteria (Kidney Disease: Improving Global Outcomes) are used to define the AKI in cardiac surgery because of their validated prognostic value in this patient population. The occurrence of a postoperative AKI, even of low severity, is accompanied by a significant increase in the duration of hospitalization and mortality. The AKI risk factors in cardiac surgery are related to the precarious clinical conditions of the patient before the surgery, to the complex surgical context, to the surgical procedures particularly the duration of extracorporeal circulation (ECC) greater than 120 min and the occurrence of a postoperative circulatory insufficiency.

AKI and inflammatory response:

The mechanisms involved in postoperative AKI in cardiac surgery, are low cardiac output, ischemia reperfusion injury (IRI), mechanical intravascular hemolysis, hypothermia, and activation of the neuroendocrine system by the ECC.

In addition, ECC triggers a secondary inflammatory response to blood contact with the ECC circuit and membranes. The secondary stimulation of immunocompetent cells accompanies secretion of many cytokines and proinflammatory mediators via the activation of nuclear transcription factors as the NFκB factor.

Of the 50 000 ECC performed per year in France, about 25% of the patients develop a Systemic Inflammatory Response Syndrome (SIRS). Although most often transient, SIRS can intensify and lead to a multi-visceral failure and to death, especially if the patient presents medical history of type 2 diabete. Increase of postoperative plasma cytokine levels has a positive predictive value on the occurrence of AKI and the risk of death.

Priming of the NLRP3 inflammasome and post ECC inflammatory response:

In addition to activation by nuclear transcription factors (NFκB), the inflammatory syndrome may develop secondarily to the activation of multi-protein platforms, called inflammasomes.

The activation of the NLRP3 inflammasome has been particularly studied in humans because of its association with multiple chronic inflammatory pathologies, infectious and cardio-metabolic diseases. Its activation is the combination of intracellular receptors like NOD-like receptors (NLR) types, ASC-like adapter proteins and pro caspase-1.

This assembly activates inflammatory caspases (caspase-1, in particular) responsible for the cleavage of pro-interleukins IL-1β and IL-18 in mature pro-inflammatory cytokines that participate in the orchestration of the inflammatory response.

Activation of the NLRP3 inflammasome requires prior priming which allows increase of NLRP3 and pro-cytokines IL1β and IL18 expressions. This priming is particularly intense in the presence of a mitochondrial dysfunction and of an increase in reactive oxygen species (ROS). Next, the activation of the NLRP3 inflammasome may be secondary to the presence of danger signals from cellular damages, such as cellular and mitochondrial debris (including mitochondrial DNA) recognized by NLRP3 receptors. Thus, preoperative mitochondrial dysfunction and its postoperative aggravation by ECC due to IRI induced by ECC represents powerful signals ,of the NLRP3 inflammasome activation.

Research hypothesis:

The hypothesis is that the preoperative priming of the NLRP3 inflammasome by a preoperative mitochondrial dysfunction is a factor favoring the occurrence of postoperative AKI after cardiac surgery with ECC.

For type 2 diabetic patients, the investigators think that preoperative mitochondrial dysfunction (mitochondrial respiration abnormalities and hyperpermeability of mitochondrial membranes) is accentuated worsening IRI induced by the ECC.

This increases postoperative release of cells and mitochondrial debris that maintain the activation of the NLRP3 inflammasome, exacerbating the inflammatory response and favoring the occurrence of AKI.


Primary objective of the research:

Describe the association between preoperatives mitochondrial dysfunction markers and the occurrence of AKI in postoperative cardiac surgery with ECC.

Secondary objective of research:

Describe, in preoperative cardiac surgery, the level of mitochondrial dysfunction according to type 2 diabetic status (inflammation-promoting factor).

Study Design


Patients Undergoing Coronary Artery Bypass Graft (CABG) Surgery Requiring Extracorporeal Circulation


Coronary Artery Bypass Graft (CABG)


CHU de Martinique




University Hospital Center of Martinique

Results (where available)

View Results


Published on BioPortfolio: 2019-10-18T11:21:42-0400

Clinical Trials [5853 Associated Clinical Trials listed on BioPortfolio]

Graft Patency of QFR-guided Versus Angio-guided Coronary Artery Bypass Grafting

Coronary artery bypass grafting(CABG) is the golden standard for severe coronary artery disease(CAD), the current surgery strategy is mainly based on coronary angiography(CAG), but many tr...

Radial Artery Bypass Graft Study of Tromsø

The purpose of this study is to answer, among others, the following questions: 1) What are the outcomes when using the radial artery as a bypass graft in coronary artery bypass surgery (CA...

MEND-CABG (MC-1 to Eliminate Necrosis and Damage in Coronary Artery Bypass Graft Surgery)

The purpose of this study is to determine whether MC-1 is effective and safe in reducing cardiovascular and neurological events in patients undergoing high-risk coronary artery bypass surg...

A Study of RO4905417 in Patients Undergoing Coronary Artery Bypass Graft (CABG) Surgery

This randomized double-blind, placebo-controlled study will evaluate the efficacy and safety of RO4905417 in the prevention of saphenous vein graft disease in patients undergoing elective ...

A Safety and Efficacy Study to Confirm the Cardioprotective Effects of MC-1 in Patients Undergoing High-Risk CABG

The purpose of this study is to determine the effect of MC-1 on the combined incidence of cardiovascular death and nonfatal myocardial infarction (MI) up to and including 30 days following...

PubMed Articles [28100 Associated PubMed Articles listed on BioPortfolio]

Synchronous Carotid Endarterectomy and Coronary Artery Bypass Graft (CABG) versus staged Carotid Artery Stenting and CABG for Patients with Concomitant Severe Coronary and Carotid Stenosis: a Systematic Review and Meta-analysis.

Due to the systemic nature of atherosclerosis, medium and large arteries at different sites are commonly simultaneously affected. As a result, severe coronary artery disease (CAD) requiring coronary a...

"Synchronous versus Staged Carotid Endarterectomy (CEA) and Coronary Artery Bypass Graft (CABG) for Patients with Concomitant Severe Coronary and Carotid Artery Stenosis: a Systematic Review and Meta-analysis".

Due to the systemic nature of atherosclerosis, arteries at different sites are commonly simultaneously affected. As a result, severe Coronary Artery Disease (CAD) requiring Coronary Artery Bypass Graf...

Multiple Coronary Artery Bypass Grafting for Kawasaki Disease-Associated Coronary Artery Disease.

Although coronary artery bypass grafting (CABG) is the preferred choice for advanced Kawasaki disease (KD)-associated coronary artery disease, graft design such as number of grafts or type of conduits...

Impact of Controlling Nutritional Status Score (CONUT) and Prognostic Nutritional Index (PIN) on Patients Undergoing Coronary Artery Bypass Graft Surgery.

The aim of this study is to evaluate the negative effect of malnutrition in patients with coronary artery disease who are undergoing coronary artery bypass graft surgery.

Comparison of SYNTAX Score I and SYNTAX Score II for Predicting Postoperative Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Graft Surgery.

Atrial fibrillation is a frequent cause of morbidity following coronary artery bypass grafting (CABG). SYNTAX score II (SSII) is associated with outcomes in patients undergoing coronary revascularizat...

Medical and Biotech [MESH] Definitions

Direct myocardial revascularization in which the internal mammary artery is anastomosed to the right coronary artery, circumflex artery, or anterior descending coronary artery. The internal mammary artery is the most frequent choice, especially for a single graft, for coronary artery bypass surgery.

Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion.

Coronary artery bypass surgery on a beating HEART without a CARDIOPULMONARY BYPASS (diverting the flow of blood from the heart and lungs through an oxygenator).


A complication of INTERNAL MAMMARY-CORONARY ARTERY ANASTOMOSIS whereby an occlusion or stenosis of the proximal SUBCLAVIAN ARTERY causes a reversal of the blood flow away from the CORONARY CIRCULATION, through the grafted INTERNAL MAMMARY ARTERY (internal thoracic artery), and back to the distal subclavian distribution.

More From BioPortfolio on "Role of Mitochondrial Dysfunction in the Occurrence of Acute Kidney Injury (AKI) in Postoperative Cardiac Surgery"

Quick Search

Relevant Topic

Surgical treatments
Surgery is a technology consisting of a physical intervention on tissues. All forms of surgery are considered invasive procedures; so-called "noninvasive surgery" usually refers to an excision that does not penetrate the structure being exci...

Searches Linking to this Trial