Transplant Renal Artery Stenosis: Observation Versus Stenting

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Transplant Renal Artery Stenosis

Intervention / Treatment
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* Diagnostic Test: Intra-arterial digital subtraction angiography


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Observational arm<br>Patients recruited to this arm will undergo no intervention. | |
| Active Comparator: Interventional arm<br>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<br>* Invasive intra-arterial angiography, with intra-arterial stent placement if a stenosis is confirmed<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplant, Transplant renal artery stenosis