Telomere Biology and AKI in Cardiac Surgery
Condition: Acute Kidney Injury; Heart Valve Diseases; Coronary Artery Disease
MeSH terms: Acute Kidney Injury; Coronary Artery Disease; Heart Valve Diseases
Study type: Observational [Patient Registry]

Summary: 
      The purpose of this study is to investigate whether biomarkers of cell senescence and aging
      can predict the development of acute kidney injury following cardiac surgery.
    

Detailed description: 
      Patients with pre-operative renal dysfunction are at increased risk of developing cardiac
      surgery associated acute kidney injury (AKI) but a proportion of patients with normal kidney
      function will also be affected. Studies show that patients developing AKI post cardiac
      surgery have a poorer long term prognosis, even if their kidney function subsequently returns
      to normal However, the cause for this is not currently understood. We postulate that a
      unifying mechanism makes such patients more susceptible to developing post-operative AKI and
      of having an overall worse long term prognosis. We suggest that this mechanism is reduced
      regenerative capacity of tissues. To test this hypothesis we will measure several markers of
      cell senescence and aging including telomere length, telomerase activity, and DNA methylation
      status.

      Previous animal studies have shown that reduced telomere length and telomerase activity in
      mice increases their susceptibility to ischaemia induced renal injury. The current study will
      look at whether a similar association is seen in humans, using cardiopulmonary bypass as a
      mechanism for studying ischaemia/inflammatory induced kidney injury. It aims to answer the
      primary research question: Are telomere length and telomerase activity related to the
      development of acute kidney injury following cardiac surgery? The presence of such an
      association would provide new avenues in the development of biomarkers to predict outcomes
      following cardiac surgery. In addition to scoring tools currently in clinical practice, such
      biomarkers might allow better risk stratification of patients undergoing cardiac surgery.

      Patient Registry and sample storage: Tissue samples and patient data collected in these
      patients will also form part of the Barts Cardiovascular Registry (BAR). This is a Biobank
      facility run by Barts Heart Centre in collaboration with United Kingdom (UK) Biobank. All
      aspects of patient recruitment, data collection, data storage, and data analysis will be
      covered by Standard Operating Procedures to ensure data quality of the registry.

      Quality assurance: The management team for the BAR will be responsible for auditing the
      completeness and validity of the data.

      Sample size: As we have no preceding data on a possible association with telomere biology and
      AKI post-cardiac surgery we have been unable to perform a power calculation for sample size.
      In effect, the present study will be a large pilot study looking at this association.
      Previously reported studies give an incidence of AKI following cardiac surgery of between 15
      and 25%. In order to have approximately 200 AKI patients to study, we will aim to recruit
      1000 patients. This is realistic given that the Barts Heart Centre should be performing
      approximately 50 cardiac operations per week. Once recruitment is established, an interim
      analysis will be performed to allow a more accurate estimation of sample size.

      Statistical analysis: All relevant clinical parameters will be analysed by frequencies,
      tabulations, correlations, distributions of normality and comparisons accordingly. An array
      of statistical methods will be employed for parametric and non-parametric data including
      Multivariate of all factors associated with the development of acute kidney injury following
      cardiac surgery. Receiver operator characteristic (ROC) curve analysis will be used to
      investigate clinical outcomes and the new markers of cell senescence (telomere length,
      telomerase activity, and DNA methylation status). Missing data values will be rectified where
      possible by review of the primary medical records. Missing data values due to incomplete
      sample collection will be dealt with by statistical modelling.
    

Intervention name(s): No intervention
Intervention type(s): Other
Intervention description(s): No intervention. This is an observational study of how patients' renal function responds to their surgery. The groups are defined by this response. There is no difference between clinical interventions between the two groups.
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        All patients undergoing cardiac surgery
      
Biospecimen description: 
      Blood samples collected for:

      Peripheral Blood Mononuclear Cells (PBMC) DNA extraction from buffy coat Right atrial tissue
      samples (subset) Urine and plasma/serum for urinary biomarkers (subset)
    
Keywords: Telomere; Telomerase; DNA methylation; Cell aging; Thoracic Surgery