BJA/RCoA Project Grant
The successful applicants for the BJA / RCoA Project Grant were:
Principal Applicant
Dr Gudrun Kunst
King's College Hospital, London
Title
A Novel Proteomic Analytic Approach to Identify Potential Biomarkers of Acute Kidney Injury and Failure
Amount
£62,548
Scientific Abstract
The recent introduction of highly sensitive and specific myocardial injury markers has improved treatment and survival in acute coronary syndromes. In contrast there is still demand for specific kidney injury markers in peri-operative medicine, which would lead to earlier diagnosis and treatment of acute kidney injury (AKI).
We propose a novel systematic proteomic analytic approach for identifying a sensitive and specific circulating marker of acute kidney injury. This approach has been used before, successfully identifying a novel myocardial marker in isolated perfused hearts (Jacquet et al. 2009). It includes the following sequence of novel steps:
- Analysis of the renal effluent in an ex vivo model - this minimises interference from high abundance plasma proteins.
- Extension of the washout period- this will further reduce background contamination by plasma proteins.
- Subsequent studies will be carried out on the same volume of effluent, reflecting the physiology of acute kidney injury.
- Proteomics analysis using a combination of one-dimensional gel electrophoresis with nanoflow liquid chromatography tandem mass spectrometry (LC-MS/MS) will be carried out as described before (Jacquet et al., 2009).
- Application of the latest ion trap technology (LTQ Orbitrap XL & Q-Exactive Plus) - this will increase the sensitivity of proteins identification.
- Testing for renal-specific tissue expression.
Unlike most proteomics studies, we are not searching for biomarkers in plasma and serum but in the effluent of perfused kidneys. The effluent is a crystalloid buffer and devoid of proteins other than the ones leaking from the tissue of interest. This reduction in complexity will allow for good proteomic coverage. Validation of the findings in the preclinical model will then be performed using samples from residual serum of a completed randomised trial in cardiac surgical patients of which 10% developed postoperative kidney failure (ISRCTN, reference number 49989273; Hausenloy, Kunst et al., 2014).
Please see the NIAA's position statement on the use of animals in medical research.
Principal Applicant
Professor Blair Smith
University of Dundee
Title
Preparing Exercise and Physical Activity as a Complex Intervention for Chronic Pain
Amount
£42,784
Originally submitted in the AAGBI/Anaesthesia category and funded by the BJA/RCoA.
Scientific Abstract
Chronic pain is common, debilitating and costly. Management options, such as pharmacological therapies, or specialised anaesthetic interventions, are of variable long-term benefit, are costly and associated with adverse effects. While exercise and physical activity are potentially safe and cost-effective, and are widely recommended in chronic pain, we do not know the most effective method of delivering exercise-based interventions. People with chronic pain may be particularly resistant to increasing physical activity, with fears about worsening pain or causing harm. We aim to address this knowledge gap as follows:
- Review best available evidence for exercise and physical activity interventions in chronic pain through the Cochrane Collaboration (already accepted)
- Explore outcomes and associated biopsychosocial factors between chronic pain sufferers who received different levels of exercise-based intervention, within a pain management service using a pre-existing dataset.
- Better understand beliefs about physical activity, attitudes and perceived barriers to increasing activity in a prospective survey of Pain Clinic patients. This will include theory-based, validated instruments to measure self-efficacy, perceived risk and outcome expectancies.
These three strands will be synthesised to inform the design of a multicentre trial to evaluate an exercise-based intervention for chronic pain suffers, aiming to improve pain and overall health.
