MRI in Renal Transplantation (TransRASL)

Non Contrast Magnetic Resonance Imaging to Measure Renal Transplant Perfusion and Fibrosis - Association With Function and Prognosis

Renal transplantation is the optimal method of treatment for end stage kidney disease however median lifespan of a kidney transplant is around 15 years. Existing methods of measuring transplant function and structure from blood and urine markers are imperfect; renal biopsy is often performed but is invasive. Novel methods of investigating transplant function are therefore required and emerging renal MRI sequences including ASL and diffusion weighted imaging may yield helpful biomarkers. Investigators will recruit 20 patients in the first year after transplant and measure MRI biomarkers at three time points, with correlation to existing methods of measuring transplant function.

Study Overview

• Status: Unknown
• Conditions: Chronic Kidney Diseases; End Stage Renal Disease; Renal Transplant Rejection; Kidney Transplant Failure and Rejection
• Intervention / Treatment: Diagnostic test: Magnetic resonance imaging

Detailed Description

Kidney transplantation remains the optimal therapy for patients with end stage kidney disease and is associated with significant improvements in life expectancy and quality of life compared to subjects receiving dialysis. Despite significant advances in our understanding of the immune system and development of drugs to prolong transplant function, a large number (Scottish Renal Registry data suggest between 23-35%) of transplants fail in the 10 years from operation. This may be due to a number of factors but is often due to development of transplant rejection, where the recipient's immune system damages the transplant. Early recognition and implementation of therapy is needed to dampen this response, reduce irreversible damage and preserve transplant function.

At present, transplant function and damage is measured using blood and urine tests. These are far from perfect markers because there is a delay between transplant damage and abnormalities of these tests. This time is vital for the short and long term survival of the transplant.

In the University of Glasgow, investigators have developed a new type of magnetic resonance imaging (MRI) which allows assessment of kidney blood flow and fibrosis (scarring) without the need for administration of harmful contrast agents. Arterial spin labelling magnetic resonance imaging (ASL MRI) is a non-invasive method of measuring renal perfusion using magnetised blood as endogenous contrast and investigators have validated this technique previously in both individuals with and without kidney disease. Diffusion tensor imaging (DTI) is another modality of non-contrast MRI which allows measurement of 'stiffness' of renal transplants, which represents long term scarring and fibrosis.

The investigators intend to follow up people receiving a kidney transplant for one year, collecting samples of blood, urine, and performing MR imaging at 3 time points, in order to investigate novel biomarkers of transplant function and dysfunction.

• Study Type: Observational
• Enrollment (Anticipated): 20

Contacts and Locations

• Study Contact: Name: Keith Gillis, MBChB PhD; Phone Number: 0141 330 2409; Email: keithgillis@nhs.net

Study Locations

• United Kingdom
  • Renfrewshire
    • Glasgow, Renfrewshire, United Kingdom, G12 8TA
      • Recruiting
      • University of Glasgow
      • Contact: Maureen Travers, PhD; Phone Number: 0141 232 1813; Email: Maureen.Travers@ggc.scot.nhs.uk
      • Principal Investigator: Rajan K Patel, MBChB PhD
      • Sub-Investigator: Keith A Gillis, MBChB PhD
      • Sub-Investigator: Patrick B Mark, MBChB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who have either recently received, or are undergoing assessment for kidney transplantation, will be recruited. Those receiving live donor transplants undergo surgery electively and can be approached prior to the time of transplant. Those receiving kidney transplants from the waiting list represent the majority of transplant patients, and undergo surgery at unpredictable time points depending on the availability of organs. These individuals will be approached shortly after transplantation. They will be identified from the electronic medical record and approached at the transplant assessment clinic or on the transplant ward. A participant information sheet will be given and the patient contacted after one week to confirm or refute participation.

Description

Inclusion Criteria:

• Age > 18 years
• Recent or pending kidney transplantation
• Written informed consent

Exclusion Criteria:

• Severe chronic liver, heart or lung disease
• Chronic infection
• Unable to give valid informed consent
• Known pregnancy or intent to conceive during the study period
• Any contraindicating to MRI

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Transplant; Incident patients receiving a kidney transplant for end stage kidney disease. Patients will undergo functional magnetic resonance imaging at 2 months, 6 months and 12 months following transplantation.	Diagnostic test: Magnetic resonance imaging; ASL and DWI MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in arterial spin labelling (ASL)	Renal perfusion measured by ASL MRI	Measured at 2, 6, 12 months after transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in apparent diffusion coefficient (ADC)	Renal fibrosis measured by diffusion weighted imaging (DWI) MRI	Measured at 2, 6, 12 months after transplant

Collaborators and Investigators

• Sponsor: NHS Greater Glasgow and Clyde

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2017
• Primary Completion (Anticipated): February 20, 2019
• Study Completion (Anticipated): March 20, 2019

Study Registration Dates

• First Submitted: March 3, 2018
• First Submitted That Met QC Criteria: October 12, 2018
• First Posted (Actual): October 15, 2018

Study Record Updates

• Last Update Posted (Actual): October 15, 2018
• Last Update Submitted That Met QC Criteria: October 12, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Magnetic resonance imaging; Biomarkers; Diffusion weighted imaging; Renal transplantation; Arterial spin labelling
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: GN15RE038

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Anonymized participant data may be shared with collaborators in renal imaging after study completion. Images will not be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No