Clinical trial NCT01380847: Prediction of Chronic Allograft Nephropathy
Official title: Early Prediction of Chronic Allograft Nephropathy by Non Invasive Monitoring of Urinary Cell mRNAs
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Transplantation
Kidney Disease
Kidney Failure, Chronic
Keywords: Kidney Transplantation
Allograft
Kidney failure
Chronic allograft nephropathy
Monitoring
Urine
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Fondation Centaure
name: ROTRF
First posted: 2011-06-27
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Hospitalized patients from Necker Hospital

Brief summary: 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.

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 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

Primary outcomes:
measure: Renal allograft fibrosis
timeFrame: 2 years
Secondary outcomes:
measure: Renal allograft nephropathy
timeFrame: 4 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Necker Hospital
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Dany Anglicheau, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: