Prediction of Chronic Allograft Nephropathy (Prefigur)
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|ClinicalTrials.gov Identifier: NCT01380847|
Recruitment Status : Unknown
Verified January 2016 by Assistance Publique - Hôpitaux de Paris.
Recruitment status was: Active, not recruiting
First Posted : June 27, 2011
Last Update Posted : February 1, 2016
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 or disease||Intervention/treatment|
|Kidney Transplantation Kidney Disease Kidney Failure, Chronic||Genetic: mRNAs encoding genes|
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 :||Observational|
|Actual Enrollment :||300 participants|
|Official Title:||Early Prediction of Chronic Allograft Nephropathy by Non Invasive Monitoring of Urinary Cell mRNAs|
|Study Start Date :||June 2011|
|Estimated Primary Completion Date :||June 2016|
|Estimated Study Completion Date :||October 2016|
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
- Renal allograft fibrosis [ Time Frame: 2 years ]Renal allograft fibrosis at one year posttransplantation
- 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
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
|Paris, France, 75015|
|Principal Investigator:||Dany Anglicheau, MD, PhD||Assistance Publique - Hôpitaux de Paris|