Vascular Complications After Kidney Transplantation

Official title

Vascular Complications After Kidney Transplantation: A Prospective National Multicenter Study - The DAN-PTRAIII Study

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.

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.

Interventions

• Diagnostic test Catheter-based angiography
  Catheter-based angiography performed in accordance with the study protocol.
• Diagnostic test Measurement of translesional pressure gradients
  Measurement of translesional pressure gradients performed in accordance with the study protocol.
• Diagnostic test Intravascular ultrasound (IVUS)
  Intravascular ultrasound (IVUS) performed in accordance with the study protocol.
• Procedure Percutaneous transluminal angioplasty (PTA)
  Percutaneous transluminal angioplasty (PTA) is performed in accordance with the study protocol. As a general principle, bare-metal stents (BMS) are used. Drug-eluting stents (DES) may be considered when the arterial lumen diameter is \< 4-5 mm. In stenoses where stent placement carries a risk of side-branch occlusion, PTA is performed without stent implantation and most often with a drug-coated balloon (DCB).

Primary outcome measures

• Change in measured glomerular filtration rate (mGFR). [Time frame: Baseline and 3 months post-PTA.]

Secondary outcome measures (12)

• Change in estimated glomerular filtration rate (eGFR). [Time frame: 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. [Time frame: 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. [Time frame: Baseline, 3 months, 12 months, and 24 months post-PTA.]
• Change in unattended automated office systolic blood pressure. [Time frame: Baseline, 3 months, 12 months, and 24 months post-PTA.]
• Change in 24-hour ambulatory systolic blood pressure. [Time frame: Baseline, 3 months, 12 months, and 24 months post-PTA.]
• Change in defined daily dose (DDD) of antihypertensive medications. [Time frame: Baseline, 3 months, 12 months, and 24 months post-PTA.]
• Change in the number of antihypertensive medications. [Time frame: Baseline, 3 months, 12 months, and 24 months post-PTA.]
• Change in 24-hour ambulatory systolic blood pressure adjusted for changes in antihypertensive medication. [Time frame: Baseline, 3 months, 12 months, and 24 months post-PTA.]
• Health status on 12-item Short Form Health Survey (SF-12). [Time frame: Baseline and 3 months post-PTA.]
• Number of clinical events after PTA. [Time frame: 10 years 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. [Time frame: 30 days post-PTA.]
• Doppler ultrasound. [Time frame: Baseline and 3 months post-PTA.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Denmark · 3 centers

• Aarhus University Hospital — Aarhus
• Rigshospitalet — Copenhagen
• Odense University Hospital — Odense

Identifiers

NCT: NCT07531966 · DAN-PTRAIII

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗