title: Expression of hypoxia-inducible factor-1α (HIF-1α) in infiltrating inflammatory cells is associated with chronic allograft dysfunction and predicts long-term graft survival.
abstract: BACKGROUND
  In chronic kidney failure, a hypoxic state, infiltrating inflammatory cells play a crucial role in the progression to end-stage renal disease. No studies have evaluated the influence of hypoxia and infiltrating inflammatory cells on chronic allograft dysfunction.
  
  
  METHODS
  Renal transplant recipients who underwent renal allograft biopsy with interstitial fibrosis/tubular atrophy (IF/TA) were enrolled and renal allograft tissue sections were processed for immunohistochemical staining including hypoxia-inducible factor-1α (HIF-1α), nitrotyrosine, α-smooth muscle actin and e-cadherin. Patients with total renal tissue HIF score ≥1 were defined as positive for HIF-1α. To assess the phenotype of the infiltrating cells, dual staining of HIF-1α with CD45, CD68 and CD3 was performed. The correlation between HIF-1α score and Banff's score was analysed. Clinical parameters including renal survival among patients with or without an expression of HIF-1α were compared.
  
  
  RESULTS
  Out of 55 patients enrolled, 23 patients (41.8%) had an HIF-1α score ≥1 (Group B). Compared with Group A (total renal HIF score <1), Group B had a significantly higher Banff score of interstitial infiltrates (i) (P = 0.029), vascular fibrous intimal thickening (cv) (P = 0.007) and arteriolar hyaline thickening (ah) (P = 0.026). Clinically, patients with an HIF-1α score were associated with a poor graft survival. Significantly inferior allograft survival was noted in Group B. HIF scores had an adjusted hazard ratio of 3.25 (95% confidence inteval: 1.71-6.16, P = 0.0003) in allograft failure.
  
  
  CONCLUSIONS
  We first demonstrated the expression of HIF-1α protein among infiltrating inflammatory cells in areas with IF/TA in patients with chronic allograft dysfunction.
authors.affiliation: China Medical University, Taichung, Taiwan.
authors.forename: Tung-Min
authors.initials: TM
authors.lastname: Yu
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Wen
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Li
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Cheng
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Wu
authors.forename: Cheng-Hsu
authors.initials: CH
authors.lastname: Chen
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Shu
mesh_terms: D000328:Adult; D018450:Disease Progression; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000378:metabolism* / Q000401:mortality; D016030:Kidney Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit