A Study of Novel Biomarkers of Kidney Dysfunction at Liver Transplant

NCT03376009 | Completed

• 1 other identifier: AC1
• Study Type: observational
• Target: 55
• Locations: 1 country
• Sites: 1

Brief Summary

Kidney dysfunction before and immediately after liver transplantation is common and leads to poorer outcomes, including prolonged need for post-operative intensive care, diminished graft survival, and greater risk of permanent kidney dysfunction and death. Blood creatinine level - the standard measure of kidney function - is suboptimal in people with advanced liver disease, overestimating kidney function by \>20%. There is significant concern that liver transplant recipients are at higher risk of acute kidney injury (AKI) than we can currently predict. This study aims to identify superior tests (blood/urine or imaging) for kidney dysfunction, to enable improved treatment and patient outcomes. This study aims to recruit 80-100 consecutive patients admitted to the Scottish Liver Transplant Unit (SLTU), Royal Infirmary of Edinburgh (RIE) for liver transplant assessment over a 6 month period. Permission will be sought to record the results of routine tests performed by the NHS during this assessment week. These tests include: electrocardiograph (ECG), Computed Tomography (CT) liver and abdomen, cardio-pulmonary exercise testing (CPEX), pulmonary function tests (PFTS), routine haematology and biochemistry blood tests, 24 hour urine collection and body composition analysis. In addition, we will invite participants to attend the RIE clinical research facility (CRF) for a single visit (\~2 hours) to perform extra research assessments. Blood and urine will be collected for biomarker analysis. Non-invasive assessment of cardiovascular function will be completed using cardiac bio-impedance and aortic pulse wave velocity. Examination of the blood vessels at the back of the eye will be performed using optical coherence tomography. A subgroup of 10 participants will undergo magnetic resonance imaging (MRI) of the kidneys using arterial spin labelling to identify dysregulated renal perfusion. Patients who are transplanted during the study timeframe will be asked to re-attend the CRF for repeat assessments at 6 weeks post transplantation. Funded by Scottish Liver Transplant Unit Endowment Fund

Conditions

Liver Transplantation; Liver Transplant; Complications; Kidney Dysfunction

Keywords

Biomarker

Outcome Measures

Primary Outcomes (1)

• Relationship between pre-transplant kidney function using novel biomarkers and post-transplant morbidity and mortality.

  (KIM-1, NGAL, Cystatin C)

  6 months

Secondary Outcomes (8)

• Relationship between pre-transplant kidney perfusion using non-contrast ASL-MRI and pre-transplant renal dysfunction defined by eGFR

  7 days

• Relationship between pre-transplant kidney perfusion using non-contrast ASL-MRI and post-transplant renal dysfunction defined by eGFR

  6 months

• Relationship between pre-transplant cardiac bioimpedence and post-transplant renal dysfunction

  6 months

• Relationship between pre-transplant APWV and post-transplant renal dysfunction

  6 months

• Relationship between pre-transplant plasma KIM-1 and post-transplant renal dysfunction

  6 months

Study Arms (1)

Liver transplant assessment patients

Adult patients admitted to the Scottish Liver Transplant Unit for liver transplant assessment, over a 6 month study period will be considered for recruitment. Interventions: Blood sample for serum and plasma biomarkers: Urine sample for biomarkers Cardiac bio-impedance (Cardioscreen Medis) Aortic pulse wave velocity (APWV) (TensioMed and SphygmoCor) Optical Coherence Tomography (Spectralis OCT) Arterial Spin Labelling Magnetic Resonance Imaging

Diagnostic Test: Blood sample for serum and plasma biomarkers:; Diagnostic Test: Urine sample for biomarkers; Diagnostic Test: Cardiac bio-impedance (Cardioscreen Medis); Diagnostic Test: Aortic pulse wave velocity (APWV) (TensioMed and SphygmoCor); Diagnostic Test: Optical Coherence Tomography (Spectralis OCT); Diagnostic Test: Arterial Spin Labelling Magnetic Resonance Imaging

Interventions

Blood sample for serum and plasma biomarkers: DIAGNOSTIC_TEST

Serum/plasma biomarkers: Approximately 10ml (3 teaspoons) of blood will be extracted to measure pre-specified biomarkers of renal injury including kidney injury molecule-1 (KIM-1), cystatin C and neutrophil gelatinase-associated lipocalin (NGAL). Samples will then be stored to facilitate measurement of additional biomarkers in the future.

Liver transplant assessment patients

Urine sample for biomarkers DIAGNOSTIC_TEST

Urinary biomarkers: A random urine sample will be obtained to measure urinary protein to creatinine ratio (uPCR), KIM-1 and liver-type fatty acid binding protein (L-FABP)

Liver transplant assessment patients

Cardiac bio-impedance (Cardioscreen Medis) DIAGNOSTIC_TEST

Cardiac bio-impedance - a non-invasive assessment of cardiac output, cardiac index and systemic vascular resistance index using the bio-impedence technique (Cardioscreen 1000 Medis) Cardiac bio-impedance is performed by attaching sticky electrodes to the participant's neck and thorax. These electrodes pass a very low, constant and alternating current (1.5 mA, 86 kHz) across the thorax, which is imperceptible to the patient. This provides beat by beat data on cardiac output and haemodynamic measurements.

Liver transplant assessment patients

Aortic pulse wave velocity (APWV) (TensioMed and SphygmoCor) DIAGNOSTIC_TEST

Aortic pulse wave velocity (APWV) a non-invasive measure of arterial function using oscillometric recordings to detail peripheral and central haemodynamics. This will be measured using two different techniques: TensioMed Arteriograph: After a rest period a blood pressure cuff inflates and deflates twice on the arm. This takes \~3 minutes and should cause only mild, temporary discomfort. The test will routinely be performed in duplicate to ensure accuracy of results. SphygmoCor: A pressure sensor is held over the radial pulse at the wrist to analyse the pulse wave. Then held over the carotid artery and/or femoral artery to assess the speed of the pulse wave through the body. The probe is similar to an ultrasound probe and should not cause any discomfort.

Liver transplant assessment patients

Optical Coherence Tomography (Spectralis OCT) DIAGNOSTIC_TEST

OCT is a non-invasive imaging test which uses light waves to take cross sectional images of the back of the eye. Examination of the retinal and retinal nerve fibre layer thickness, macular volume, and choroidal thickness provides an assessment of generalised systemic microvascular injury. A strong correlation between choroidal thickness and renal dysfunction has previously been shown in patients with chronic kidney disease (Balmforth C et al, JCI Insight 2016). The participant is asked to sit in front of the OCT machine and rest their chin on a support to keep it motionless. The equipment will then scan the eye without touching it. Scanning takes about 5 - 10 minutes.

Liver transplant assessment patients

Arterial Spin Labelling Magnetic Resonance Imaging DIAGNOSTIC_TEST

Magnetic resonance imaging using arterial spin labelling (ASL-MRI) This promising quantitative technique has the potential to identify dysregulated renal perfusion, stratify risk of AKI in pre-OLT patients, and to monitor alterations in renal haemodynamics in the post transplantation setting. * We aim to recruit 5 participants with 'normal' renal function (eGFR≥60ml/min/1.73m2) and a further 5 participants with 'abnormal' renal function (eGFR\<60ml/min/1.73m2) * ASL-MRI will be performed in this subgroup during the week of OLT assessment and then repeated at 6-weeks post transplantation in those participants who undergo OLT during the study period.

Also known as: ASL-MRI

Liver transplant assessment patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients who are admitted to the Royal Infirmary of Edinburgh (RIE) liver unit for liver transplant assessment over a 6-month period will be invited to join this study. They will be identified as potentially eligible by a member of their clinical care team, and thereafter will be introduced to a member of the research study team and given a participant information sheet. At present, approximately 4-5 patients are admitted for transplant assessment per week, therefore we anticipate that recruitment over a 6-month period would provide a potential of 80-100 participants.

You may qualify if:

• Male or female adults over 18 years of age
• Able to provide written informed consent and able to understand and willing to comply with the requirements of the study
• Admission for assessment for liver transplantation

You may not qualify if:

• Patients who do not have capacity to consent
• Patients being assessed for liver transplantation because of acute liver failure
• Patients who are unwilling or unable to have an MRI scan will be excluded from the ASL-MRI study sub-group

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

Royal Infirmary of Edinburgh

Edinburgh, Scotland, EH16 4SA, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood samples for serum and plasma Urine samples

MeSH Terms

Interventions

Blood Specimen Collection; Tomography, Optical Coherence

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Tomography, Optical; Optical Imaging; Diagnostic Imaging; Tomography

Study Officials

• Jonathan A Fallowfield, PhD

  University of Edinburgh, NHS Lothian

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2017
• First Posted: December 18, 2017
• Study Start: January 15, 2018
• Primary Completion: August 3, 2018
• Study Completion: September 10, 2018
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)