Using the Speckle Doppler to Quantify Blood Flow in Kidney and Pancreas Grafts
Condition: Kidney Transplant Failure and Rejection
Study type: Observational

Summary: 
      Kidney and Pancreas transplantation is considered the treatment of choice for many people
      with End Stage Renal Disease and Type 1 diabetes because quality of life and survival is
      often better after transplantation. However the quality of organs varies as does the quality
      of perfusion once they are transplanted. The immediate determinant of the survival of any
      transplanted allograft often depends on the overall quality of perfusion of the organ. The
      assessment of perfusion is currently visually and empirically done and reported by the
      surgical team, with low objectivity. The Laser Speckle Doppler technique will be used in both
      kidney and pancreas transplantation to objectively study the quality of blood flow to the
      kidney and pancreas after transplantation. This Doppler will provide continuous, non-invasive
      blood flow monitoring of the microvascular environment of the transplanted organ. The
      strength of the technique is in evaluating changes in flow over an area of interest or the
      whole transplanted organ and accurately numerically quantifying the flow. The laser speckle
      Doppler technique is now well established and has been used in various clinical and research
      setting as the most convenient means of assessing tissue blood flow. It has however not yet
      been used in kidney and pancreas transplantation.
    

Detailed description: 
      BACKGROUND After reperfusion in solid organ transplantation, the quality of organ reperfusion
      is often assessed visually and reported as good, moderate, reasonable, patchy or poor. In our
      centre a Renogram is usually performed which uses radioactive tracer which most kidney
      transplant recipients would have within 24 hours after transplantation to assess the overall
      perfusion of the allograft. The Speckle Laser Doppler is a powerful clinical tool to obtain
      full field, high resolution images of microvascular perfusion of an organ It has been used in
      many medical fields such as dermatology vascular medicine and neurosciences both in a
      research and in clinical settings. This study seeks to utilise this technique to try to
      accurately quantify perfusion in the kidney and pancreas after transplantation and to develop
      a robust numerical quantification system of reporting on organ perfusion.

      The Speckle Laser Doppler blood flow imager uses the laser speckle contrast technique to
      deliver real-time blood flow images with numerical physical data, providing outstanding
      performance in a wide range of pre-clinical and clinical research applications. This
      technique has not yet been applied for the assessment of kidney transplant perfusion
      reporting.

      RESEARCH QUESTION/AIM(S)

        1. To evaluate the use of the laser blood flow imager in both kidney and pancreas
           transplantation and obtain real time video images with physical parametric data of the
           blood flow of transplanted organs at the time of transplantation as a proof of principle
           study to accurately quantify the blood flow rate either in the whole transplanted organ
           or a specific area of interest so as to develop a robust numerical quantification system
           of reporting on the perfusion of the transplanted organ. While this technique has been
           used in neurosurgery and other clinical settings it has not been evaluated before in a
           transplant setting.

           .

        2. Measure the markers of inflammation (Hypo perfusion) and oxidative stress and attempt
           correlation with the quality of perfusion obtained.

      Objectives

      This study aims to utilise this technique to try to accurately quantify perfusion in the
      kidney and pancreas after transplantation and to develop a robust numerical quantification
      system of reporting on organ perfusion

      Outcome Circulating markers of hypo perfusion and kidney injury will be measured to include:
      lactate, glutamate, pyruvate, Interleukin 6 as well as glutathione a marker of oxidative
      stress and assess their correlation with outputs from the two devices.

      RATIONALE This study seeks to utilise this technique to try to accurately quantify perfusion
      in the kidney and pancreas after transplantation and to develop a robust numerical
      quantification system of reporting on organ perfusion.

      The moorFLPI-2 blood flow imager uses the laser speckle contrast technique to deliver
      real-time blood flow images with numerical physical data, providing outstanding performance
      in a wide range of pre-clinical and clinical research applications. This technique has not
      yet been applied for the assessment of kidney transplant perfusion reporting.

      STUDY DESIGN and METHODS of DATA COLLECTION AND DATA ANALYIS Speckle Doppler The Speckle
      Laser Doppler blood flow imager will be used to obtain real-time blood flow images at
      reperfusion and immediately thereafter this imaging will occur immediately after the surgery
      when the patient is still under anaesthetic it will take approximately 15 minutes. Initially
      these images with the flow parametric data will be stored on a laptop which comes with the
      rental equipment. However once the study is complete, all images and data will be stored on a
      desktop/drive in the department along with other departmental research data confidentially.
      The software integrated in the equipment incorporates multiple blood flow parameters and a
      statistical analytical package for an exhaustive analysis of various parameters. The Speckle
      Laser Doppler has two low power visible aiming lasers that indicate the approximate centre of
      the image. The aiming lasers will appear as a single point at a distance of 25 cm. As the
      distance is increased or decreased from 25 cm, the aiming lasers will appear as two separate
      points with the centre of the image being located at the midpoint between them. The aiming
      lasers can be turned on or off by pressing the button on the scan head or from the System
      Setup window in the PC software.

      The moorFLPI-2 measurement software provides two measurement modes that can be used
      separately or in combination:

        -  Multi-image measurement mode.

        -  Single point measurement mode. The multi-image mode setting will be used as it measures
           flux over regular timed intervals and that is what is required for us to quantify the
           perfusion as compared to a single point measurement mode which measures the average flux
           at a single point in time.

      Blood samples Concurrently blood samples will be obtained on each patient on Day 0 (day of
      transplantation), after reperfusion to measure markers of hypo perfusion and kidney injury:
      lactate, glutamate, pyruvate, Interleukin 6 as well as glutathione a marker of oxidative
      stress

      Clinical Follow up

      Patients will be monitored for 3 years following their transplant to look for any transplant
      related problems which may relate to the quality of the organ as assessed by speckle Doppler.

      Sample size and Statistical analysis This is an exploratory study to evaluate the use of
      Doppler in kidney transplants and as such sample size is mainly dictated by pragmatic
      considerations and what is available for the duration of hiring the device. Nevertheless
      sample of 68 is sufficient to provide reasonable precision for the agreement and correlation
      tests intended for this study in an exploratory level. The analyses will be mainly
      descriptive. Tests will be exploratory and in the view of generating information for future
      larger studies.

      Research Q1 The software integrated in the equipment incorporates multiple blood flow
      parameters and a statistical analytical package for an exhaustive analysis of various
      parameters. The comparison between the 2 methods for measuring blood flow will be assessed
      for agreement using the appropriate statistical methodology.

      The continuous variables for markers of inflammation, circulating markers of hypo perfusion
      and oxidative stress will also be assessed for any correlation with speckle Doppler perfusion
      measurements.

      Events at the end of 3 years follow up will be compared with the blood flow measurements in
      categorical analysis.

      STUDY SETTING Our unit performs the largest number of kidneys transplants in the UK so has
      access to a large number of samples for this project.

      All members of the team have academic track records and participate in several on-going
      research projects. Current research projects are investigating cardiovascular disease, kidney
      perfusion, and MR imaging.
    

Intervention name(s): Speckle Doppler imaging; Blood sample
Intervention type(s): Other; Other
Intervention description(s): Speckle Doppler Laser imaging; Blood sampling
Other intervention name(s): Laser Imaging; Venepuncture
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        This study plans to recruit all recipients of, both kidney and pancreas transplants within
        a 14-week course of the study (Period of Lease of the Speckle Laser Doppler).

        It is expected that approximately n=60 kidney transplants (Living Donor, DBD and DCD and
        Marginal Kidneys) and n=8 pancreas transplant patients will be recruited in this study
        period.

        This will provide a range of grafts of varying quality of perfusion for assessment
      
Biospecimen description: 
      Plasma and cell pellets following blood centrifugation will be collected and stored.