Vascular Complications After Kidney Transplantation

N/ARecruitingNCT07531966

University of Aarhus60 enrolled

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.

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 Type

Interventions

Catheter-based angiographyDIAGNOSTIC_TEST

Catheter-based angiography performed in accordance with the study protocol.

Measurement of translesional pressure gradientsDIAGNOSTIC_TEST

Measurement of translesional pressure gradients performed in accordance with the study protocol.

Intravascular ultrasound (IVUS)DIAGNOSTIC_TEST

Intravascular ultrasound (IVUS) performed in accordance with the study protocol.

Percutaneous transluminal angioplasty (PTA)PROCEDURE

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).

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1\. At least one of the following clinical criteria (1 or 2) must be fulfilled: 1. 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. 2. 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: 1. CT or MR angiography demonstrating a lumen reduction ≥50%. 2. Doppler ultrasound showing: 1. Peak systolic velocity in the renal artery ≥200 cm/s and a renal renal ratio (velocity at stenosis / velocity in distal artery) \>4. 2. 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: 1. Stenosis ≥70%. 2. 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: 1. Inability to provide informed consent. 2. Concurrent biopsy demonstrating rejection requiring treatment. 3. Pregnancy. 4. Previous PTA of the same vessel. 5. Patients unable to tolerate any form of antithrombotic therapy and therefore not eligible for stent placement.

Outcomes

Primary Outcomes

Change in measured glomerular filtration rate (mGFR).

Change in measured glomerular filtration rate (mGFR) at 3 months post-PTA compared with baseline.

Time frame: Baseline and 3 months post-PTA.

Secondary Outcomes

Change in estimated glomerular filtration rate (eGFR).

Change in estimated glomerular filtration rate (eGFR) measured on day 1, day 7, day 21, at 6 weeks, at 3 and 12 months, and annually thereafter for up to 10 years post-PTA, compared with baseline.

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.

Change in home systolic blood pressure measured on day 7, day 21, at 6 weeks, at 3 and 12 months, and annually thereafter for up to 10 years post-PTA, compared with baseline.

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.

Change in attended automated office systolic blood pressure measured at 3, 12, and 24 months post-PTA, compared with baseline.

Time frame: Baseline, 3 months, 12 months, and 24 months post-PTA.

Change in unattended automated office systolic blood pressure.

Change in unattended automated office systolic blood pressure measured at 3, 12, and 24 months post-PTA, compared with baseline.

Time frame: Baseline, 3 months, 12 months, and 24 months post-PTA.

Change in 24-hour ambulatory systolic blood pressure.

Change in 24-hour ambulatory systolic blood pressure measured at 3, 12, and 24 months post-PTA, compared with baseline.

Time frame: Baseline, 3 months, 12 months, and 24 months post-PTA.

Change in defined daily dose (DDD) of antihypertensive medications.

Change in defined daily dose (DDD) of antihypertensive medications at 3, 12, and 24 months post-PTA compared with baseline.

Time frame: Baseline, 3 months, 12 months, and 24 months post-PTA.

Change in the number of antihypertensive medications.

Change in the number of antihypertensive medications at 3, 12, and 24 months post-PTA compared with baseline.

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.

Change in 24-hour ambulatory systolic blood pressure measured at 3, 12, and 24 months post-PTA, compared with baseline, adjusted for changes in antihypertensive medication (5 mmHg per DDD).

Time frame: Baseline, 3 months, 12 months, and 24 months post-PTA.

Health status on 12-item Short Form Health Survey (SF-12).

Change in 12-item Short Form Health Survey (SF-12) scores at 3 months post-PTA, compared with baseline. Scores range from 0 to 100, with higher scores indicating better physical and mental health functioning.

Time frame: Baseline and 3 months post-PTA.

Number of clinical events after PTA.

Cardiovascular and renal events are defined according to the criteria used in the DAPA-CKD study, with the modification that end-stage kidney disease is defined exclusively as either kidney transplantation or chronic dialysis. After PTA treatment, the following clinical events will be recorded for 10 years: 1. Cardiovascular death 2. Renal death 3. Death from non-cardiovascular and non-renal causes 4. Stroke 5. Myocardial infarction 6. Hospitalization for heart failure 7. Reduction in eGFR ≥50% from baseline for ≥28 days, not fulfilling the definition of end-stage kidney disease 8. End-stage kidney disease, defined as kidney transplantation or chronic dialysis for ≥28 days 9. Biopsy-proven rejection 10. Need for repeat PTA due to restenosis or in-stent thrombosis

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.

All SAEs, procedure-related adverse events (≤24 hours), and postoperative adverse events (\>24 hours) occurring within 30 days after the procedure will be systematically recorded. Events include, but are not limited to: 1. Death from any cause 2. Rupture, dissection, occlusion, or perforation of the graft artery 3. Stent thrombosis post-PTA 4. Embolic adverse events to the kidney or peripheral circulation (upper or lower extremity depending on access route) 5. Bleeding requiring transfusion 6. Embolization or nephrectomy due to bleeding or other adverse event 7. Access-related complications requiring treatment. Defined as bleeding at the puncture site necessitating additional hospitalization, transfusion, or surgical intervention, including thrombin injection for pseudoaneurysm. The definition also includes thrombosis of the access vessel causing ischemic symptoms or requiring surgical intervention. 8. Need for acute dialysis 9. Clinical events as defined above

Time frame: 30 days post-PTA.

Doppler ultrasound.

Diagnostic utility and predictive value for treatment response to PTA.

Time frame: Baseline and 3 months post-PTA.

Invasive pressure measurements across stenoses.

Diagnostic utility and predictive value for treatment response to PTA.

Time frame: Baseline and 3 months post-PTA.

Intravascular ultrasound.

Diagnostic utility and predictive value for treatment response to PTA.

Time frame: Baseline and 3 months post-PTA.

Non-invasive fractional flow reserve computed tomography (FFR-CT) / computational fluid dynamics (CFD) simulation.

Diagnostic utility and predictive value for treatment response to PTA.

Time frame: Baseline and 3 months post-PTA.

Functional magnetic resonance imaging.

Diagnostic utility and predictive value for treatment response to PTA.

Time frame: Baseline and 3 months post-PTA.

Vascular Complications After Kidney Transplantation

Overview

Conditions

Interventions

Eligibility

Locations (3)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts