BJA/RCoA Project Grant

A Novel Proteomic Analytic Approach to Identify Potential Biomarkers of Acute Kidney Injury and Failure

Dr Gudrun Kunst

At least one out of three patients suffers from acute kidney injury (AKI) in the intensive care unit or after heart surgery and the chances of dying can be eight times higher in these patients. There are many causes of AKI, including peri-operative lack of oxygen supply, dyes used in medical imaging, and kidney poisoning from bacterial infections.

Diagnosis of acute heart injury, for example after a heart attack, is quick, easy and reliable with blood sample analysis of a sensitive and specific biomarker. In contrast to the rapid diagnosis of acute heart injury, the diagnosis of AKI is delayed by 1-2 days with the currently used blood tests. This results in a missed opportunity for treatment due to the time lag between the onset of kidney injury and the diagnosis of AKI.

We have recently described a novel method to identify a marker for heart injury, which promises to have a different and potentially improved time window of diagnosing heart injury. We now propose a similar approach, which includes single organ perfusion of the kidney under normal and injured (or ischaemic) conditions. Thereafter, a comprehensive analysis of proteins or blood markers takes place, which is called proteomics. The comparison of the proteomic analysis of the normal and the injured kidney will reveal potential markers suitable for the diagnosis of AKI. These kidney markers will then be validated and compared with current kidney markers in patients undergoing heart operations.

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Preparing Exercise and Physical Activity as a Complex Intervention for Chronic Pain

Professor Blair Smith

Background
Chronic (i.e. long-term) pain affects around 1 in 5 adults. For 1 in 20 it is so intense and disabling that it seriously affects all aspects of health. Successful management is challenging to achieve. Most people with chronic pain are management by their GP, using a range of painkillers. Side effects often occur as a result, with increasing concern over long-term health effects, and cure is rarely achieved. Recent focus is on non-drug treatments including psychological and physical therapies. Exercise and physical activity are thought to be beneficial in chronic pain, to provide a potentially cost-effective, healthy option, alongside other treatments. However, we do not know the best ways of delivering or advising exercise-based treatments; their overall effectiveness and safety are unknown; and many people with chronic pain are reluctant or scared to increase physical activity.

Aims
This study aims to establish the evidence base for providing treatments based on exercise or physical activity to adults with chronic pain; to better understand how specialist exercise based management impacts on pain and disability; and to explore possible barriers to increasing physical activity. This will help optimise design of future large scale study of exercise in chronic pain management.

Objectives

  • To summarise systematically the best available evidence for the effectiveness of physical activity and exercise in chronic pain.
  • To analyse existing data from a Pain Management Programme, comparing outcomes between individuals whose input was primarily exercise-based, and those whose input was primarily psychology-based.
  • To identify attitudes, beliefs and perceived barriers to increasing physical activity among a sample of patients attending chronic pain services.

Methods

  • The Cochrane Collaboration has produced many detailed reviews, which identify the effectiveness of different exercise-based treatment for different chronic pain conditions. We will examine all of these systematically, to measure the overall effectiveness of exercise in chronic pain. We will look for aspects of each treatment (who delivers it, how, when and to whom) that are associated with improved pain and quality of life, and any that are associated with increased risk. We are already working with the Cochrane Collaboration, and have secured their academic support for this 'review of reviews'.
  • Data from the Lothian Chronic Pain Service have been collected routinely, at baseline and after treatment from ~750 individuals, over 3 years, and is available for analysis. These include details of pain type and severity, treatments given, and the outcomes of treatment. We will compare outcomes between those who have, and who have not received exercise-based treatments.
  • A questionnaire survey of 200 people attending our pain clinics will explore their attitudes and beliefs about exercise, perceived barriers to increasing physical activity, and potential approaches to overcoming these. The questionnaire will include established and validated instruments.

Outputs
This study will provide the best current evidence for exercise-based treatments in chronic pain, and inform the design of the most effective intervention. This will be tested in a future trial, funding for which will be sought.