Expression of Fibrosis-related Genes in Human Renal Allografts with Interstitial Fibrosis and Tubular Atrophy

Background: Gene expression analysis of fibrosis-related genes may became useful for the early identification of fibrosis processes. We quantitatively assessed messenger RNA transcripts of the CTGF, TGF-β and KIM-1 genes, in biopsy samples from renal transplant recipients with graft dysfunction, to test the hypothesis that in patients with chronic disease of the renal transplant, these molecules could be markers of the development and severity of graft fibrosis.

Methods: Ninety-six kidney transplant recipients who undertook 121 indication graft biopsies between January 2008 and December 2009 were included. Patients and biopsies were classified into 4 major diagnostic groups according to the Banff 2007 classification: acute tubular necrosis (ATN; n = 20), acute rejection (AR; n = 58), acute calcineurin inhibitor nephrotoxicity (CIN; n = 13) and interstitial fibrosis and tubular atrophy (IF/TA; n = 30).

Results: Messenger RNA transcripts of the CTGF and TGF-β genes were significantly higher in IF/TA compared with all other conditions. Messenger RNA transcripts of the KIM-1 gene in the IF/TA group were higher than in the CIN group. In addition, it was observed that gene expression of CTGF, TGF-β and KIM-1 increased with severity of fibrosis observed in the pathological examinations.

Conclusions: Gene expression evaluation of the kidney graft tissue may be used to improve pathological diagnosis and perhaps for the future development of noninvasive biomarkers.