Overview
- 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.
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.
Eligibility
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) \>4.
- 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 ≤0.8.
- 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.
- Pregnancy.
- Previous PTA of the same vessel.
- Patients unable to tolerate any form of antithrombotic therapy and therefore not eligible for stent placement.
