- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01380847
Prediction of Chronic Allograft Nephropathy (Prefigur)
Early Prediction of Chronic Allograft Nephropathy by Non Invasive Monitoring of Urinary Cell mRNAs
The investigators have shown that epithelial-to-mesenchymal transition (EMT) markers in early protocol biopsies of the renal allograft predicts the progression of fibrosis during the first year post-transplantation.
The investigators will develop a non-invasive approach for predicting fibrosis as a substitute for the invasive allograft biopsy procedure, by longitudinal assessment of the mRNA expression level of genes implicated in EMT/fibrogenesis and inflammation in urinary cells from kidney transplant recipients during the first year post-transplantation.
Study Overview
Status
Intervention / Treatment
Detailed Description
mRNA profiling of urinary cells is fast evolving as a non-invasive substitute for invasive biopsy procedures employed for predicting renal allograft outcomes. This technique has been successfully used to develop biomarkers of acute rejection, but has not been evaluated for the diagnosis of allograft fibrosis.
The progressive scarring process of an allograft, called chronic allograft nephropathy (CAN), remains the chief cause of kidney transplant failure. We have shown by immunohistochemistry that epithelial changes suggestive of epithelial-to-mesenchymal transition (EMT) in early protocol biopsies predict the progression of CAN during the first year post-transplantation. Our preliminary results suggest that the urinary cell mRNA profile is altered in kidney transplant recipients (KTRs) with CAN.
The purpose of this study is to evaluate urine from KTRs during the first year post-transplantation to assess whether mRNA levels of genes involved in EMT/fibrogenesis can diagnose and predict CAN, and identify patients at risk of chronic allograft dysfunction.
The scientific underpinnings for our hypotheses are provided by (a) data showing that urinary cell mRNAs predict pathological changes (i.e., acute rejection) in renal allografts; and (b) our previous studies suggesting that CAN is characterized by altered urinary cell mRNA levels.
Our specific aims are to (1) investigate whether the levels of 21 mRNAs encoding genes involved in EMT/fibrogenesis and the alloimmune response are a sensitive and specific non-invasive diagnostic test for CAN in renal allografts; (2) determine whether mRNA profiles of sequential urine specimens can predict the development of CAN during the first year post-transplantation; and (3) determine whether mRNA profiles of sequential urine specimens predict the subsequent development of graft dysfunction as assessed by estimated GFR at 12, 24 and 36 months after transplantation.
Eligible patients will be consecutive KTRs from Necker Hospital during one year (n≈180). Urine samples will be collected at 1, 3, 6, 9 and 12 months post-transplantation, and 21 mRNAs involved in EMT/fibrogenesis and the alloimmune response will be quantified by PCR. Allograft fibrosis will be quantified by image analysis, developed in our unit. Urinary cell mRNA profiles will be correlated with data from protocol biopsies (3 months and 1 year) and glomerular filtration rate (GFR) at 1 and 3 years. Diagnostic and prognostic accuracy of mRNA levels will be determined.
The identification of molecular markers of CAN may allow for early diagnosis of CAN (before the onset of fixed renal injury) and thus the development of specific therapeutic interventions.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
-
Paris, France, 75015
- Necker Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion criteria :
- male and female adult recipients
- patients undergoing primary or re-do deceased-donor or living-donor kidney transplantation
- ability to provide informed consent
Exclusion criteria :
- patients undergoing combined organ transplantation
- Contraindication to protocol allograft biopsy
- Inability or unwillingness of a participant to provide informed consent.
- HCV infected
- HIV infected
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Renal allograft nephropathy
To evaluate urine from KTRs during the first year post-transplantation to assess whether mRNA levels of genes involved in EMT/fibrogenesis can diagnose and predict CAN, and identify patients at risk of chronic allograft dysfunction
|
investigate whether the levels of 21 mRNAs encoding genes involved in EMT/fibrogenesis and the alloimmune response are a sensitive and specific non-invasive diagnostic test for CAN in renal allografts
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Renal allograft fibrosis
Time Frame: 2 years
|
Renal allograft fibrosis at one year posttransplantation
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Renal allograft nephropathy
Time Frame: 4 years
|
Progression of renal allograft fibrosis between 3 months and one year posttransplantation Renal allograft function at 3 year posttransplantation
|
4 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Dany Anglicheau, MD, PhD, Assistance Publique - Hôpitaux de Paris
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NI 09045
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Kidney Failure, Chronic
-
Centre Hospitalier Universitaire DijonTerminatedEnd-stage Chronic Kidney FailureFrance
-
Angiodynamics, Inc.TerminatedChronic Kidney Disease | Acute Kidney Injury | Acute Renal Failure | Renal Failure Chronic Contrast InducedUnited States
-
Baxter Healthcare CorporationRecruitingAcute Kidney Failure | Chronic Kidney FailureChina
-
Texas A&M UniversityWithdrawnChronic Kidney FailureUnited States
-
University of WashingtonJohns Hopkins University; National Institute of Diabetes and Digestive and... and other collaboratorsRecruitingChronic Kidney Diseases | Acute Renal Failure | Acute Renal Injury | Acute Kidney Failure | Chronic Renal Insufficiency | Kidney Failure, Acute | Renal Insufficiency, Acute | Acute Renal Insufficiency | Acute Kidney Insufficiency | Renal Failure, Acute | Chronic Kidney Insufficiency | Chronic Renal Diseases | Kidney... and other conditionsUnited States
-
Hopital Jean MinjozUnknownCardiac Surgical Procedures | Preoperative KIDNEY FAILURE, CHRONIC | Postoperative KIDNEY FAILURE, ACUTEFrance
-
Nantes University HospitalNot yet recruiting
-
Ozge AKBABAAtaturk UniversityCompletedChronic Kidney FailureTurkey
-
Chinese PLA General HospitalCompletedKidney Failure,ChronicChina
-
Fatma Alzahraa Mohamed Ibrahim Hassan HaggagUnknown
Clinical Trials on mRNAs encoding genes
-
University Hospital, ToulouseInstitut National de la Santé Et de la Recherche Médicale, France; Clinical... and other collaboratorsCompleted
-
University of Western SydneyActive, not recruitingMild Cognitive Impairment | Mild Dementia | Healthy Older AdultsAustralia
-
National Taiwan University HospitalNational Science Council, TaiwanCompleted
-
The First Affiliated Hospital of Guangzhou Medical...UnknownNon-small Cell Lung CancerChina
-
Copenhagen University Hospital at HerlevUnknown
-
Assistance Publique - Hôpitaux de ParisUnknown
-
IRCCS Eugenio MedeaRecruitingPreterm Birth | Parent-Child Relations | EpigeneticsItaly
-
Mayo ClinicNational Cancer Institute (NCI)RecruitingAnatomic Stage IV Breast Cancer AJCC v8 | Recurrent Breast Carcinoma | Invasive Breast Carcinoma | Metastatic Breast AdenocarcinomaUnited States
-
Peking University Third HospitalPeking University First Hospital; Wuhan Asia Heart HospitalCompletedCoronary Heart Disease
-
University of South-Eastern NorwayNorwegian University of Science and TechnologyCompleted