Vascular Complications After Kidney Transplantation: A Prospective National Multicenter Study - The DAN-PTRAIII Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- University of Aarhus
- Enrollment
- 60
- Locations
- 3
- Primary Endpoint
- Change in measured glomerular filtration rate (mGFR).
Study Overview
Brief Summary
- To determine the incidence of arterial inflow problems and venous outflow problems as causes of impaired renal function and/or treatment-resistant hypertension after kidney transplantation, when all kidney-transplant recipients in Denmark are evaluated according to uniform, well-defined clinical criteria.
- To investigate the efficacy and safety of catheter-based balloon treatment (percutaneous transluminal angioplasty, PTA) for these vascular complications, of which transplant renal artery stenosis is by far the most common.
- To assess whether novel imaging and functional diagnostic methods can predict treatment response.
Detailed Description
Kidney transplantation is performed 250-300 times annually in Denmark and substantially improves survival, quality of life, and reduces the burden of comorbidities in patients with end-stage kidney disease. Despite these benefits, vascular complications, particularly transplant renal artery stenosis (TRAS), remain a major cause of morbidity. Reported incidence of TRAS varies widely (1-23%), reflecting retrospective study designs and inconsistent diagnostic criteria. TRAS are classified into three main types: anastomotic (TRAS-A), post-anastomotic (TRAS-P), and long-segment bend/kink (TRAS-B), with most cases diagnosed within the first two years post-transplant. Severe stenoses can critically impair graft perfusion, leading to reduced renal function and treatment-resistant hypertension.
Percutaneous transluminal angioplasty (PTA) for TRAS is a well-established procedure performed according to the same principles as coronary balloon angioplasty; however, the role of stent placement remains uncertain. PTA without stenting is associated with higher restenosis rates compared to PTA with stenting, yet evidence regarding graft function, survival, and blood-pressure control remains conflicting.
Adverse events related to PTA occur in approximately 10% of patients and are generally mild. Serious adverse events are observed in fewer than 5% of patients and include procedure-related internal bleeding and vascular access-site complications. Severe internal bleeding may require blood transfusion and endovascular vessel occlusion and can, in rare cases, result in loss of the transplanted kidney. Access-site vascular complications may present as bleeding, thrombosis, or pseudoaneurysm.
Against this background, the nationwide prospective multicentre DAN-PTRAIII study aims to establish the true incidence of arterial inflow and venous outflow problems in Danish kidney-transplant recipients, evaluate the efficacy and safety of balloon angioplasty, and explore novel imaging and functional diagnostic methods for predicting treatment response.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •1. At least one of the following clinical criteria (1 or 2) must be fulfilled:
- •Graft dysfunction, defined by at least one of the following:
- •Acute reduction in estimated glomerular filtration rate (eGFR) >15% on two consecutive measurements at least 2 weeks apart, with other causes excluded (rejection, obstruction, infection).
- •eGFR <50% of the expected value 30 days after kidney transplantation of unknown cause.
- •Decline in eGFR >30% after initiation of an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker.
- •Persistent resistant hypertension for more than 6 weeks after kidney transplantation, defined as:
- •24-hour ambulatory systolic blood pressure >130 mmHg despite treatment with at least three classes of antihypertensive medication at maximally tolerated doses (including diuretics, if tolerated).
- •Together with at least one of the following radiological criteria:
- •CT or MR angiography demonstrating a lumen reduction ≥50%.
- •Doppler ultrasound showing:
- •Peak systolic velocity in the renal artery ≥200 cm/s and a renal renal ratio (velocity at stenosis / velocity in distal artery) >
- •Acceleration time >70 ms in intrarenal arteries.
- •2. In cases of strong clinical suspicion of a vascular complication where CT or MR angiography cannot reliably exclude graft artery or vein stenosis, patients may be referred for confirmatory invasive investigations.
- •Before PTA, catheter-based angiography and translesional pressure measurements are performed to confirm whether the patient meets the radiological eligibility criterion for PTA:
- •Stenosis ≥70%.
- •Stenosis 50-69% if at least one of the following criteria is met:
- •Mean translesional pressure gradient ≥10 mmHg.
- •Systolic pressure gradient ≥20 mmHg.
- •Renal Pd/Pa ≤0.
- •If pressure measurements cannot be obtained, treatment is based on the operator's clinical judgement.
Exclusion Criteria
- •Inability to provide informed consent.
- •Concurrent biopsy demonstrating rejection requiring treatment.
- •Previous PTA of the same vessel.
- •Patients unable to tolerate any form of antithrombotic therapy and therefore not eligible for stent placement.
Arms & Interventions
Kidney Transplant Recipients
Patients who meet well-defined clinical and radiological criteria for significant vascular complications after kidney transplantation, with transplant renal artery stenosis being by far the most common.
Intervention: Catheter-based angiography (Diagnostic Test)
Kidney Transplant Recipients
Patients who meet well-defined clinical and radiological criteria for significant vascular complications after kidney transplantation, with transplant renal artery stenosis being by far the most common.
Intervention: Measurement of translesional pressure gradients (Diagnostic Test)
Kidney Transplant Recipients
Patients who meet well-defined clinical and radiological criteria for significant vascular complications after kidney transplantation, with transplant renal artery stenosis being by far the most common.
Intervention: Intravascular ultrasound (IVUS) (Diagnostic Test)
Kidney Transplant Recipients
Patients who meet well-defined clinical and radiological criteria for significant vascular complications after kidney transplantation, with transplant renal artery stenosis being by far the most common.
Intervention: Percutaneous transluminal angioplasty (PTA) (Procedure)
Outcomes
Primary Outcomes
Change in measured glomerular filtration rate (mGFR).
Time Frame: Baseline and 3 months post-PTA.
Change in measured glomerular filtration rate (mGFR) at 3 months post-PTA compared with baseline.
Secondary Outcomes
- Number of clinical events after PTA.(10 years post-PTA.)
- Change in estimated glomerular filtration rate (eGFR).(Baseline, Day 1, Day 7, Day 21, 6 weeks, 3 months, 12 months, and annually thereafter for up to 10 years post-PTA.)
- Change in home systolic blood pressure.(Baseline, Day 7, Day 21, 6 weeks, 3 months, 12 months, and annually thereafter for up to 10 years post-PTA.)
- Change in attended automated office systolic blood pressure.(Baseline, 3 months, 12 months, and 24 months post-PTA.)
- Change in unattended automated office systolic blood pressure.(Baseline, 3 months, 12 months, and 24 months post-PTA.)
- Change in 24-hour ambulatory systolic blood pressure.(Baseline, 3 months, 12 months, and 24 months post-PTA.)
- Change in defined daily dose (DDD) of antihypertensive medications.(Baseline, 3 months, 12 months, and 24 months post-PTA.)
- Change in the number of antihypertensive medications.(Baseline, 3 months, 12 months, and 24 months post-PTA.)
- Change in 24-hour ambulatory systolic blood pressure adjusted for changes in antihypertensive medication.(Baseline, 3 months, 12 months, and 24 months post-PTA.)
- Health status on 12-item Short Form Health Survey (SF-12).(Baseline and 3 months post-PTA.)
- Number of serious adverse events (SAEs), procedure-related adverse events (≤24 hours), and postoperative adverse events (>24 hours) occurring within 30 days after the procedure.(30 days post-PTA.)
- Doppler ultrasound.(Baseline and 3 months post-PTA.)
- Invasive pressure measurements across stenoses.(Baseline and 3 months post-PTA.)
- Intravascular ultrasound.(Baseline and 3 months post-PTA.)
- Non-invasive fractional flow reserve computed tomography (FFR-CT) / computational fluid dynamics (CFD) simulation.(Baseline and 3 months post-PTA.)
- Functional magnetic resonance imaging.(Baseline and 3 months post-PTA.)