title: Unilateral Partial Nephrectomy with Warm Ischemia Results in Acute Hypoxia Inducible Factor 1-Alpha (HIF-1α) and Toll-Like Receptor 4 (TLR4) Overexpression in a Porcine Model.
abstract: Ischemia/reperfusion (I/R) during partial nephrectomy (PN) contributes to acute kidney injury (AKI), which is inaccurately assessed using existent clinical markers of renal function. We evaluated I/R-related changes in expression in hypoxia inducible factor 1α (HIF-1α) and toll-like receptor 4 (TLR4), within kidney tissue and peripheral blood leukocytes (PBL) in a porcine model of PN.
  
  
  
  Three adult pigs each underwent unilateral renal hilar cross clamping for 180 min followed by a 15 min reperfusion. The contralateral kidney served as control. Biopsies of clamped kidneys were obtained at baseline (time 0), every 60 min during the hypoxic phase, and post-reperfusion. Control kidneys were biopsied once at 180 min. Peripheral blood was sampled at time 0, every 30 min during the hypoxic phase, and post-reperfusion. HIF-1α and TLR4 expression in kidney tissue and PBL were analyzed by Western blotting. I/R-related histological changes were assessed.
  
  
  
  Expression of HIF-1α in clamped kidneys and PBL was below detection level at baseline, rising to detectable levels after 60 min of hypoxia, and continuing to rise throughout the hypoxic and reperfusion phases. Expression of TLR-4 in clamped kidneys followed a similar trend with initial detection after 30-60 min of hypoxia. Control kidneys exhibited no change in HIF-1α or TLR-4 expression. I/R-related histologic changes were minimal, primarily mild tubular dilatation.
  
  
  
  In a porcine model of PN, HIF-1α and TLR4 exhibited robust, I/R-related increases in expression in kidney tissue and PBL. Further studies investigating these molecules as potential markers of AKI are warranted.
authors.affiliation: Division of Urology and General Surgery, Department of Surgery, Rutgers, Robert Wood Johnson Medical School, New Brunswick, NJ, United States of America.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Division of Urology and General Surgery, Department of Surgery, Rutgers, Robert Wood Johnson Medical School, New Brunswick, NJ, United States of America.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Haimovich
authors.affiliation: Division of Urology and General Surgery, Department of Surgery, Rutgers, Robert Wood Johnson Medical School, New Brunswick, NJ, United States of America.|Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, United States of America.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Kwon
authors.affiliation: Rutgers University, New Brunswick, NJ, United States of America.
authors.forename: Tyler
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Pathology and Laboratory Medicine, Rutgers, Robert Wood Johnson Medical School, New Brunswick, NJ, United States of America.
authors.forename: Billie
authors.initials: B
authors.lastname: Fyfe-Kirschner
authors.affiliation: Division of Urology and General Surgery, Department of Surgery, Rutgers, Robert Wood Johnson Medical School, New Brunswick, NJ, United States of America.
authors.forename: Ephrem Odoy
authors.initials: EO
authors.lastname: Olweny
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D009392:Nephrectomy; D013552:Swine; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051197:Toll-Like Receptor 4