Transplant Renal Artery Stenosis: Observation Versus Stenting (TRASOS)

Transplant Renal Artery Stenosis: Observation Versus Stenting - a Feasibility Study

Transplant renal artery stenosis (TRAS) is abnormal narrowing of the main blood vessel to the kidney transplant and has historically been considered a surgical complication. In heart transplantation, it has long been recognised that rejection can cause narrowing of the heart's blood vessels, and that this complication is the leading cause of heart transplant failure. It is reasonable to assume that this process may also occur in kidney transplantation, which could contribute to premature transplant failure. However, in kidney transplantation it is also likely that other factors, such as surgical factors, traditional cardiovascular risk factors and immunological factors, contribute to the development of TRAS. Given that the disease processes that cause TRAS are not fully understood, at present there is no consensus among kidney doctors on the best means of treating patients diagnosed with TRAS. The aim of the proposed study is to investigate the involvement of these different processes in the development of TRAS, and investigate the optimal way to diagnose and manage TRAS.

At present, there is no standard recommendation for how to treat patients with TRAS. This is partly due to the fact that patients with TRAS may have a broad array of symptoms: Some may have no symptoms, other may have problems with high blood pressure or fluid accumulation, and others may have severe transplant dysfunction. In most transplant centres, patient TRAS and severe symptoms will undergo IADSA and a stent will be placed to open the narrowing. However, it is not clear how best to manage patients with TRAS who have mild to moderate symptoms. We propose to recruit 36 such patients to a clinical study and split them into two groups: One group to undergo IADSA with possible stent placement, and one group to be closely observed. We will then compare transplant function, and other outcomes, after one year between the two groups.

Study Overview

• Status: Recruiting
• Conditions: Transplant Renal Artery Stenosis
• Intervention / Treatment: Diagnostic test: Intra-arterial digital subtraction angiography

Detailed Description

Transplant renal artery stenosis (TRAS) is abnormal narrowing of the main blood vessel to the kidney transplant and has historically been considered a surgical complication. In heart transplantation, it has long been recognised that rejection can cause narrowing of the heart's blood vessels, and that this complication is the leading cause of heart transplant failure. It is reasonable to assume that this process may also occur in kidney transplantation, which could contribute to premature transplant failure. However, in kidney transplantation it is also likely that other factors, such as surgical factors, traditional cardiovascular risk factors and immunological factors, contribute to the development of TRAS. Given that the disease processes that cause TRAS are not fully understood, at present there is no consensus among kidney doctors on the best means of treating patients diagnosed with TRAS. The aim of the proposed study is to investigate the involvement of these different processes in the development of TRAS, and investigate the optimal way to diagnose and manage TRAS.

At present, there is no standard recommendation for how to treat patients with TRAS. This is partly due to the fact that patients with TRAS may have a broad array of symptoms: Some may have no symptoms, other may have problems with high blood pressure or fluid accumulation, and others may have severe transplant dysfunction. In most transplant centres, patient TRAS and severe symptoms will undergo IADSA and a stent will be placed to open the narrowing. However, it is not clear how best to manage patients with TRAS who have mild to moderate symptoms. We propose to recruit 36 such patients to a clinical study and split them into two groups: One group to undergo IADSA with possible stent placement, and one group to be closely observed. We will then compare transplant function, and other outcomes, after one year between the two groups.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Paul Martin; Phone Number: 02033136641; Email: paul.martin9@nhs.net

Study Locations

• United Kingdom
  • England
    • London, England, United Kingdom, W12 0HS
      • Recruiting
      • Imperial College Healthcare NHS Trust
      • Contact: Michelle Willicombe, MBBS MD; Phone Number: 02033136641; Email: michelle.willicombe@nhs.net
      • Contact: Paul Martin, MBBS MSc; Email: paul.martin9@nhs.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

- 1. Renal transplant recipient with a diagnosis of TRAS by radiological imaging, and an MDT decision to proceed with diagnostic IADSA.

2. Aged 18 years and over 3. Able to give informed consent

Exclusion Criteria:

- 1. Estimated GFR <10mls/min/1.73m2 or dialysis dependence 2. Contraindication to angiography (e.g. allergy to radiological contrast) 3. Patients with clinical features of severe TRAS (eg. resistant hypertension, pulmonary oedema and/or rapidly deteriorating function).

4. Any condition or co-morbidity which in the investigator's opinion would make the patient ineligible for the trial or unlikely to adhere to trial procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Observational arm; Patients recruited to this arm will undergo no intervention.
Active Comparator: Interventional arm; Patients recruited to this arm will undergo intra-arterial digital subtraction angiography, with or without intra-arterial stent placement	Diagnostic test: Intra-arterial digital subtraction angiography; Invasive intra-arterial angiography, with intra-arterial stent placement if a stenosis is confirmed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in eGFR between both arms	measure of kidney transplant function	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in estimated glomerular filtration rate (eGFR)	measure of kidney transplant function	at baseline, then 1, 3, 6 and 12-months following diagnosis
Change in mean arterial blood pressure (BP), systolic BP and diastolic BP	Measure of cardiovascular health	at baseline, then 1, 3, 6 and 12-months following diagnosis
Average number of anti-hypertensive medications	measure of cardiovascular health	at baseline, then 1, 3, 6 and 12-months following diagnosis
Urinary protein : creatinine ratio (UPCR) measurement	measure of proteinuria	at baseline, then 1, 3, 6 and 12-months following diagnosis
Donor-specific antibody (DSA) free survival	measure of time free from presence of donor-specific antibody in participant's serum	1 year
Rejection free survival	measure of time free from histologically proven kidney transplant rejection	1 year
Renal allograft failure	Measure of time free from kidney transplant failure	1 year
Patient survival	measure of patient survival	1 year
Requirement for intervention (primary angiogram in observational group, secondary angiogram in interventional group)	Quantification of patients that require intervention	1 year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse event reporting	reporting of any adverse events that afflict study participants	1 year

Collaborators and Investigators

• Sponsor: Imperial College Healthcare NHS Trust
• Investigators: Principal Investigator: Michelle Willicombe, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2021
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: September 7, 2021
• First Submitted That Met QC Criteria: September 7, 2021
• First Posted (Actual): September 16, 2021

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Transplant renal artery stenosis; Kidney transplant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Kidney Diseases; Urologic Diseases; Pathological Conditions, Anatomical; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Constriction, Pathologic; Renal Artery Obstruction
• Other Study ID Numbers: 20HH6286

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No