title: Expression of hypoxia-inducible factor-1α and hepatocyte growth factor in development of fibrosis in the transplanted kidney.
abstract: Late renal graft loss is associated with interstitial fibrosis. Hypoxia-inducible factor-1α (HIF-1α) is thought to facilitate fibrosis through interaction with TGF-β1, while hepatocyte growth factor (HGF) may act antifibrotic in the kidney allograft. The aim of this study was to investigate the expression of HIF-1α and HGF in protocol biopsies as possible prognostic biomarkers for renal fibrosis. Thirty-nine renal transplant recipients were included in the study. Protocol biopsies performed 1 and 2 years after transplantation were used for immunohistochemistry analysis. The correlation between HIF-1α/HGF and the Banff score was analysed. In addition, progression in renal fibrosis and graft survival among recipients with high or low expression of HIF-1α/HGF after transplantation was compared. There was no significant correlation between fibrosis and the HIF-1α expression 1 and 2 years after transplantation, but an inverse significant correlation between the HGF expression and the fibrosis score 1 year after transplantation was shown. Even when adjusting for human leucocyte antigen mismatches, there was a significant relationship between fibrosis and HGF expression. Graft survival was not significantly correlated to HIF-1α or HGF at 1 year, although the trend was towards better graft survival with high HGF. HGF may have antifibrotic effects in human renal transplants. (Central.Denmark.Region.Committee number: 1-10-72-318-13).
authors.affiliation: Research Laboratory for Biochemical Pathology, Department of Clinical Medicine, Aarhus University, Aarhus C, Denmark.
authors.forename: Terese
authors.initials: T
authors.lastname: Kellenberger
authors.forename: Niels
authors.initials: N
authors.lastname: Marcussen
authors.forename: Jens R
authors.initials: JR
authors.lastname: Nyengaard
authors.forename: Lise
authors.initials: L
authors.lastname: Wogensen
authors.forename: Bente
authors.initials: B
authors.lastname: Jespersen
mesh_terms: D000328:Adult; D005260:Female; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D006085:Graft Survival; D017228:Hepatocyte Growth Factor / Q000032:analysis / Q000502:physiology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis / Q000502:physiology*; D007668:Kidney / Q000473:pathology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017228:Hepatocyte Growth Factor
keywords: fibrosis; graft survival; hepatocyte growth factor; hypoxia-inducible factor-1α; renal transplantation