title: Hypoxia-Inducible Factor-1α Expression in Kidney Transplant Biopsy Specimens After Reperfusion Is Associated With Early Recovery of Graft Function After Cadaveric Kidney Transplantation.
abstract: BACKGROUND
  Ischemia/reperfusion injury during kidney transplantation (KTx) delays allograft recovery. Hypoxia-inducible factor-1α (HIF-1α) is the key regulator of the protective response to ischemia/reperfusion injury. We evaluated the impact of the HIF-1α signaling pathway on allograft recovery during cadaveric KTx.
  
  
  METHODS
  Between 1996 and 2015, 46 patients underwent cadaveric KTx. The expression levels of HIF-1α-related proteins, including phosphoinositide 3-kinase, phosphorylated (p)-Akt, p-mammalian target of rapamycin, p-Eukaryotic translation initiation factor 4E, p-S6 ribosomal protein, and HIF-1α, were immunohistochemically evaluated and semi-quantitatively scored in graft biopsy specimens after 1 hour of revascularization. Ten kidney biopsy specimens collected during donor nephrectomy for living KTx were used as controls. Delayed graft function (DGF) was defined as the need for dialysis within 1 week of KTx. We compared the staining scores of each protein and several clinical parameters between patients with and those without DGF.
  
  
  RESULTS
  Expression levels of all six proteins in specimens after revasculization were elevated compared with those in controls. Thirty-five patients had DGF. Expression levels of PI3K, p-AKT, p-mTOR, p-eIF4E, and HIF-1α were significantly higher in patients without DGF than in those with DGF. Univariate analysis identified expression levels of p-Akt, p-S6, and HIF-1α, in addition to donor type (heart beating/non-heart beating), cold ischemic time, and donor age as significant predictors of DGF. Of these, only expression levels of HIF-1α and donor type were independently associated with DGF in multivariate analysis.
  
  
  CONCLUSIONS
  Up-regulation of HIF-1α in allografts after reperfusion may be a predictor of early recovery after cadaveric KTx.
authors.affiliation: Division of Urology, Department of Surgery Related, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. Electronic address: odachin0419@yahoo.co.jp.
authors.forename: T
authors.initials: T
authors.lastname: Oda
authors.affiliation: Division of Urology, Department of Surgery Related, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ishimura
authors.affiliation: Division of Urology, Department of Surgery Related, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Yokoyama
authors.affiliation: Division of Urology, Department of Surgery Related, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Division of Urology, Department of Surgery Related, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Miyake
authors.affiliation: Division of Urology, Department of Surgery Related, Faculty of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Fujisaw
mesh_terms: D000818:Animals; D001706:Biopsy; D051799:Delayed Graft Function / Q000378:metabolism*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis*; D016030:Kidney Transplantation; D008297:Male; D015427:Reperfusion Injury / Q000378:metabolism; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit