CE-US in Renal Transplantation

A PILOT, EXPLORATIVE STUDY TO IDENTIFY CONTRAST-ENHANCED ULTRASOUND (CE-US) PATTERNS THAT CHARACTERIZE ACUTE ALLOGRAFT REJECTION AND OTHER CAUSES OF ACUTE ALLOGRAFT DYSFUNCTION IN RENAL TRANSPLANT RECIPIENTS

Acute allograft dysfunction is often observed in the first weeks after kidney transplantation. Renal biopsy is universally considered the gold standard procedure for differential diagnosis of acute allograft dysfunction secondary to intraparenchymal causes. Kidney biopsy, however, is an invasive procedure that is time and cost consuming. Moreover, it may but not contribute to clinical diagnosis in about 10% of cases because of the impossibility to perform the analysis or of inadequacy of the biopsy sample. Availability or readily applicable non-invasive procedures might therefore allow increasing the performance of differential diagnosis of allograft dysfunction. In the recent years, a novel US imaging technique, namely contrast-enhanced ultrasound (CE-US),has been developed. The agent used in this study, Sonovue microbubbles consist of a central sulphur hexafluoride core with a surrounding phospholipid monolayer and last for several minutes in the systemic circulation before spontaneous degradation with absorption of the gaseous component by the lungs and the phospholipid shell by the liver. With the use of gasfilled microbubbles that act as scatterers within the blood stream and the development of low-MI ultrasound techniques that allow the visualization of the bubbles without destroying them, it is possible to improve the depiction of vessels and have access to structural and functional information on the microcirculation. Moreover SonoVue microbubbles are not nephrotoxic and can be safely used to evaluate kidney disfunction.

Thus, whether a. different patterns of parenchymal perfusion detected by CE-US can be associated with different patterns of renal graft involvement during acute renal function deterioration and b. whether, conversely, different patterns of parenchymal perfusion detected by CE-US may help predicting different patterns of renal involvement will be investigated in 20 deceased or living donor kidney graft recipients.

Study Overview

• Status: Completed
• Conditions: Renal Transplantation
• Intervention / Treatment: Procedure: Contrast-enhanced ultrasound (CE-US); Device: SonoVue

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Bergamo, Italy
    • Unità di Nefrologia e Dialisi - A.O. Papa Giovanni XXIII

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Age > 18 years
• Kidney transplantation with a functioning graft (dialysis independence)
• Clinical indication to histologic evaluation of the kidney graft
• Written Informed consent (according to the Declaration of Helsinki guidelines)

Exclusion criteria:

• Specific contraindications to histologic evaluation of the kidney graft (bleeding time > 15 min, intra-abdominal implantation of the graft)
• Known hypersensitivity to sulphur hexafluoride or to any of the components of SonoVue.
• Recent Acute Coronary Syndrome (ACS) or clinically unstable ischaemic cardiac disease, including: evolving or ongoing myocardial infarction, typical angina at rest within last 7 days, significant worsening of cardiac symptoms within last 7 days, recent coronar artery intervention or other factors suggesting clinical instability (for example, recent deterioration of ECG, laboratory or clinical findings), acute cardiac failure, Class III/IV cardiac failure, or severe rhythm disorders.
• Right-to-left shunts, severe pulmonary hypertension (PAP >90 mmHg

Study Plan

How is the study designed?

Design Details

• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Contrast-enhanced ultrasound (CE-US); Ce-US is performed by contrast agent infusion SonoVue. The acquisition protocol will consist of two different administrations of SonoVue, performed 10 minutes apart. In the first session, SonoVue microbubbles will be administered as a fast 1.5 ml bolus immediately followed by 5 ml saline solution. In the second session, max 2 vials (9.6 ml) of SonoVue will be infused at an infusion rate between 0.5 and 1.0 ml/min.

Procedure: Contrast-enhanced ultrasound (CE-US); Device: SonoVue

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in complete or partial occlusion of pre-glomerular arteries and arterioles;changes in functional (and reversible) vasoconstriction of pre-glomerular arteries and arterioles.	All examinations will be done by Contrast-enhanced ultrasound. Contrast agent wash-in (sec) and contrast agent wash-out (sec) will be assessed.	At week 1,2,3 and 4.
Changes in interstitial edema and cellular infiltration with tubulitis; changes in interstitial edema with tubular cell necrosis.	All examinations will be done by Contrast-enhanced ultrasound. Contrast agent wash-in (sec) and contrast agent wash-out (sec) will be assessed.	At week 1,2,3 and 4.
Changes in complete or partial occlusion of pre-glomerular arteries and arterioles; changes in functional (and reversible) vasoconstriction of pre-glomerular arteries and arterioles.	All examinations will be done by Contrast-enhanced ultrasound. Contrast agent wash-in (sec) and contrast agent wash-out (sec) will be assessed.	At month 2,3,4,5,6,7,8,9,10,11,and 12.
Changes in interstitial edema and cellular infiltration with tubulitis; changes in interstitial edema with tubular cell necrosis.	All examinations will be done by Contrast-enhanced ultrasound. Contrast agent wash-in (sec) and contrast agent wash-out (sec) will be assessed.	At month 2,3,4,5,6,7,8,9,10,11,and 12.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in CE-US parameters from episodes of acute allograft deterioration versus baseline	All examinations will be done by Contrast-enhanced ultrasound. Contrast agent wash-in (sec) and contrast agent wash-out (sec) will be assessed.	At the time of acute allograft episode, assessed up to 12 months.

Collaborators and Investigators

• Sponsor: Mario Negri Institute for Pharmacological Research

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: February 25, 2013
• First Submitted That Met QC Criteria: March 20, 2013
• First Posted (Estimate): March 21, 2013

Study Record Updates

• Last Update Posted (Estimate): October 29, 2013
• Last Update Submitted That Met QC Criteria: October 28, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Contrast-enhanced ultrasound; Renal Transplant; Acute allograft rejection
• Other Study ID Numbers: CE-US; 2010-019126-13 (EudraCT Number)