Vascular Complications After Kidney Transplantation

Официальное название

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

Обзор

* 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.

Подробное описание

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.

Вмешательства

• Диагностический тест Catheter-based angiography
  Catheter-based angiography performed in accordance with the study protocol.
• Диагностический тест Measurement of translesional pressure gradients
  Measurement of translesional pressure gradients performed in accordance with the study protocol.
• Диагностический тест Intravascular ultrasound (IVUS)
  Intravascular ultrasound (IVUS) performed in accordance with the study protocol.
• Процедура 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).

Первичные конечные точки

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

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Дания · 3 центра

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

Идентификаторы

NCT: NCT07531966 · DAN-PTRAIII

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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