Prediction of Chronic Allograft Nephropathy

NCT ID: NCT01380847

Last Updated: 2026-01-02

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 300 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2011-06-30
• Study Completion Date: 2012-04-19

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.

Conditions

Kidney Transplantation; Kidney Disease; Kidney Failure, Chronic

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

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

mRNAs encoding genes

Intervention Type: GENETIC

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

Interventions

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

Intervention Type: GENETIC

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondation Centaure

OTHER

Sponsor Role: collaborator

ROTRF

UNKNOWN

Sponsor Role: collaborator

URC-CIC Paris Descartes Necker Cochin

OTHER

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dany Anglicheau, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Necker Hospital

Paris, , France

Countries

France

References

Galichon P, Amrouche L, Hertig A, Brocheriou I, Rabant M, Xu-Dubois YC, Ouali N, Dahan K, Morin L, Terzi F, Rondeau E, Anglicheau D. Urinary mRNA for the Diagnosis of Renal Allograft Rejection: The Issue of Normalization. Am J Transplant. 2016 Oct;16(10):3033-3040. doi: 10.1111/ajt.13891. Epub 2016 Jul 8.

Reference Type: RESULT

PMID: 27232948 (View on PubMed)

Other Identifiers

NI 09045

Identifier Type: -

Identifier Source: org_study_id