ERKNet

The European Rare Kidney Disease Reference Network

  

Research Project

Project Title:

IDENTIFICATION OF BIOMARKERS FOR EARLY DIAGNOSIS OF KIDNEY TRANSPLANT REJECTION

Project Type:

Translational research

Disease group(s):

Pediatric kidney transplantation

Project Summary:

Kidney transplantation is the treatment of choice for pediatric end-stage kidney disease. Although immunosuppressive therapy has improved survival graft rate, kidney transplant patients require a life-long surveillance to avoid rejection. Biopsy is the gold standard in renal allograft failure diagnosis, that is the main cause of late kidney rejection. However, biopsy is an invasive method that is not risk-free. Emerging data support the presence of biomarkers predictive of rejection in easily accessible biological fluids. Among these, extracellular vesicles (EVs) could represent a sensitive tool for monitoring renal graft status in kidney transplantation.
Objectives: An interdisciplinary approach will be used to correlate clinical, histological, immunological, biochemical and molecular data using a defined timeline monitoring model, in order to identify early predictive allograft rejection biomarkers. This study will lead to the development of novel methods to precociously diagnose, treat, and eventually prevent renal rejection, thus reducing the need of renal biopsy.
Research plan: We will consider 50 children transplanted in our UOSD Pediatric Nephrology Dialysis Transplantation Center of Padua from 2016 to the end of 2019. To date we have recruited 40 patients. Urine, blood and tissue samples deriving from protocols biopsy are collected at T0 (before transplanting) and at 6-12-24 months after transplant. Multidisciplinary skills and application of innovative technologies (Fluorescent bead immunoassay, ddPCR, LC-MS/MS, Reverse Phase Protein Assay) will be applied to characterize the EVs origins and composition.
Anticipated results: Identification of biomarkers will allow to: 1) predict the development of acute rejection and chronic allograft nephropathy 2) minimize the need for invasive allograft biopsy 3) enhance therapies capable of preserving graft function 4) allow to create a tailored immunosuppressive therapy for pediatric graft recipients.

Lead principal investigator(s):

luisa murer, padova
paola cogo, udine

Co-investigator(s):

Susanna Negrisolo, Padova
Andrea Carraro, Padova
Elisa Benetti, Padova
manuela simonato, udine

Project Period:

01/2019   -   12/2020

Sponsors:

Local resources

Project web page:

https://www.irpcds.org/partiti-nuovi-progetti-di-ricerca-innovativi-per-2-milioni-di-euro-irp-e-un-modello-conferma-il-sab/

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