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Prediction of Chronic Allograft Nephropathy (Prefigur)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01380847
First Posted: June 27, 2011
Last Update Posted: February 1, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Fondation Centaure
ROTRF
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
  Purpose

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.


Condition Intervention
Kidney Transplantation Kidney Disease Kidney Failure, Chronic Genetic: mRNAs encoding genes

Study Type: Observational
Study Design: Observational Model: Cohort
Official Title: Early Prediction of Chronic Allograft Nephropathy by Non Invasive Monitoring of Urinary Cell mRNAs

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Renal allograft fibrosis [ Time Frame: 2 years ]
    Renal allograft fibrosis at one year posttransplantation


Secondary Outcome Measures:
  • 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


Biospecimen Retention:   Samples With DNA
RNA profiling of urinary cells in kidney transplant recipients

Enrollment: 300
Study Start Date: June 2011
Estimated Study Completion Date: October 2016
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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
Genetic: mRNAs encoding genes
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

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.

  Eligibility

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Hospitalized patients from Necker Hospital
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01380847


Locations
France
Necker Hospital
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Fondation Centaure
ROTRF
Investigators
Principal Investigator: Dany Anglicheau, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01380847     History of Changes
Other Study ID Numbers: NI 09045
First Submitted: June 23, 2011
First Posted: June 27, 2011
Last Update Posted: February 1, 2016
Last Verified: January 2016

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Kidney Transplantation
Allograft
Kidney failure
Chronic allograft nephropathy
Monitoring
Urine

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic