Clinical trial NCT01815320: CE-US in Renal Transplantation
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Renal Transplantation
Keywords: Renal Transplant
Contrast-enhanced ultrasound
Acute allograft rejection
Lead sponsor: Mario Negri Institute for Pharmacological Research
Sponsor class: OTHER
First posted: 2013-03-21
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Changes in complete or partial occlusion of pre-glomerular arteries and arterioles;changes in functional (and reversible) vasoconstriction of pre-glomerular arteries and arterioles.
timeFrame: At week 1,2,3 and 4.
measure: Changes in interstitial edema and cellular infiltration with tubulitis; changes in interstitial edema with tubular cell necrosis.
timeFrame: At week 1,2,3 and 4.
measure: Changes in complete or partial occlusion of pre-glomerular arteries and arterioles; changes in functional (and reversible) vasoconstriction of pre-glomerular arteries and arterioles.
timeFrame: At month 2,3,4,5,6,7,8,9,10,11,and 12.
measure: Changes in interstitial edema and cellular infiltration with tubulitis; changes in interstitial edema with tubular cell necrosis.
timeFrame: At month 2,3,4,5,6,7,8,9,10,11,and 12.
Secondary outcomes:
measure: Changes in CE-US parameters from episodes of acute allograft deterioration versus baseline
timeFrame: At the time of acute allograft episode, assessed up to 12 months.
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: Unità di Nefrologia e Dialisi - A.O. Papa Giovanni XXIII
Study officials:
References: