Vascular Complications After Kidney Transplantation (DAN-PTRAIII)

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

• 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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Kidney Transplant; Complications; Kidney Transplant Recipient; Transplant Renal Artery Stenosis; Renovascular Hypertension; Renovascular Disease; Renal Transplant Graft Failure
• Intervention / Treatment: Diagnostic test: Catheter-based angiography; Diagnostic test: Measurement of translesional pressure gradients; Diagnostic test: Intravascular ultrasound (IVUS); Procedure: Percutaneous transluminal angioplasty (PTA)

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 Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Mark Reinhard, MD, PhD; Phone Number: +45 40460321; Email: markrein@rm.dk
• Study Contact Backup: Name: Henrik Birn, MD, DMSc; Email: hb@clin.au.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Recruiting
    • Aarhus University Hospital
    • Contact: Mark Reinhard, MD, PhD; Email: markrein@rm.dk
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
    • Contact: Søren S Sørensen, MD, DMSc; Email: Soeren.Schwartz.Soerensen@regionh.dk
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Claus Bistrup, MD, PhD; Email: Claus.Bistrup@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

National prospective multicenter study with a primary endpoint at 3 months and annual follow-up for up to 10 years post-intervention, evaluating renal function, blood pressure, and clinical events.

Patients with vascular complications, predominantly transplant renal artery stenosis (TRAS) following kidney transplantation, who meet at least one of the clinical inclusion criteria, may be enrolled in the study.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

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.

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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in measured glomerular filtration rate (mGFR).	Change in measured glomerular filtration rate (mGFR) at 3 months post-PTA compared with baseline.	Baseline and 3 months post-PTA.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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).	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.	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: Cardiovascular death; Renal death; Death from non-cardiovascular and non-renal causes; Stroke; Myocardial infarction; Hospitalization for heart failure; Reduction in eGFR ≥50% from baseline for ≥28 days, not fulfilling the definition of end-stage kidney disease; End-stage kidney disease, defined as kidney transplantation or chronic dialysis for ≥28 days; Biopsy-proven rejection; Need for repeat PTA due to restenosis or in-stent thrombosis	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: Death from any cause; Rupture, dissection, occlusion, or perforation of the graft artery; Stent thrombosis post-PTA; Embolic adverse events to the kidney or peripheral circulation (upper or lower extremity depending on access route); Bleeding requiring transfusion; Embolization or nephrectomy due to bleeding or other adverse event; 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.; Need for acute dialysis; Clinical events as defined above	30 days post-PTA.
Doppler ultrasound.	Diagnostic utility and predictive value for treatment response to PTA.	Baseline and 3 months post-PTA.
Invasive pressure measurements across stenoses.	Diagnostic utility and predictive value for treatment response to PTA.	Baseline and 3 months post-PTA.
Intravascular ultrasound.	Diagnostic utility and predictive value for treatment response to PTA.	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.	Baseline and 3 months post-PTA.
Functional magnetic resonance imaging.	Diagnostic utility and predictive value for treatment response to PTA.	Baseline and 3 months post-PTA.

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Odense University Hospital; Aarhus University Hospital; Rigshospitalet, Denmark; Aalborg University Hospital; Holbaek Sygehus; Gødstrup Hospital; The Augustinus Foundation, Denmark.; Amsterdam UMC
• Investigators: Principal Investigator: Mark Reinhard, MD, PhD, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2026
• Primary Completion (Estimated): March 31, 2031
• Study Completion (Estimated): June 1, 2031

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Percutaneous transluminal angioplasty; Kidney Transplant; Complications; Transplant Renal Artery Stenosis; renovascular disease
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Heart Diseases; Hypertension; Hypertension, Renal; Heart Failure; Hypertension, Renovascular; Investigative Techniques; Therapeutics; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Catheterization; Endovascular Procedures; Vascular Surgical Procedures; Cardiovascular Surgical Procedures; Minimally Invasive Surgical Procedures; Diagnostic Imaging; Ultrasonography; Angioplasty; Ultrasonography, Interventional
• Other Study ID Numbers: DAN-PTRAIII

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No