Research Group

  • Dr. Jan Anthoine Bruijn, Principal Investigator
  • Dr. Johan de Fijter, Co-Investigator
  • M.Sc. Marian Roos-van Groningen, Graduate Student
  • Dr. Ineke ten Berge, Collaborator
  • Dr. Sandrine Florquin, Collaborator

Location

  • Leiden University Medical Center, Leiden, The Netherlands

Title

  • Prognostic Markers in Protocolized Renal Allograft Biopsies

Chronic allograft nephropathy (CAN) is the major cause of renal graft loss. Interstitial fibrosis is generally seen in renal biopsies of patients with CAN. Myofibroblasts are the main effector cells responsible for the fibrosis and largely originate from tubular epithelial cells by epithelial-to-mesenchymal transition. Once CAN is histologically detectable in the biopsy, therapy is not effective. Due to the shortage of organs available for transplantation, it is essential to find and validate early molecular prognostic markers before the onset of overt fibrosis. Timely identification of high-risk patients enables more intense immunosuppressive medicative dosing and clinical follow-up. In addition, it will open the way to early, and thereby more efficient molecular intervention strategies.

We hypothesize that early gene expression levels in renal transplant biopsies are additive surrogate markers to histological and clinical parameters for outcome and may render novel targetable genes. This will be tested using protocolized transplant biopsies at 6 and 12 months from a prospective multicenter study. Outcome parameters are the extent of fibrosis in the 6-month biopsy, the change in the extent of fibrosis between 6 and 12 months, and the change in renal function between 6 months and 3 years. In the project we will focus 1.) on genes that have previously been shown in experimental studies to be involved either in promotion or inhibition of fibrogenesis and epithelial-to-mesenchymal transition, and 2.) on novel genes, identified by microarray analyses on kidney transplant tissue, which may exert anti- or pro-fibrogenic activities. Our goal is to determine the predictive value of mRNA levels and corresponding protein levels for graft outcome in comparison to that of histological and clinical variables.

mRNA and protein expression for multiple genes early after kidney transplantation are expected to be used as novel surrogate markers. Such markers may represent novel drug targets in the prevention or limitation of progressive allograft damage.

Final Report