title: A comparison of inflammatory, cytoprotective and injury gene expression profiles in kidneys from brain death and cardiac death donors.
abstract: BACKGROUND
  The superior long-term survival of kidneys from living donors (LDs) compared with kidneys from donation-after-brain-death (DBD) and donation-after-cardiac-death (DCD) donors is now well established. However, comparative studies on transcriptional changes that occur at organ retrieval and during and after cold ischemia (CI) are sparse.
  
  
  METHODS
  Using a rat model, we used qRT-PCR to examine expression levels of inflammatory, cytoprotective, and injury genes at different time points after organ retrieval. Cleaved caspase-3 was used to evaluate early apoptosis in DCD and DBD kidneys.
  
  
  RESULTS
  Immediately after retrieval, we found massive up-regulation of proinflammatory genes interleukin-1β, interleukin-6, tumor necrosis factor-α, monocyte chemotactic protein-1, P-selectin, and E-selectin in DBD compared with LD and DCD kidneys. A significant increase in the expression of injury markers Kim-1, p21, and the cytoprotective gene heme oxygenase-1 accompanied this. Bax was increased in DCD kidneys, and Bcl-2 was decreased in DBD kidneys. After 2 hr of CI in the LD group and 18 hr in the DBD and DCD groups, gene expression levels were similar to those found after retrieval. During 18 hr of cold storage, expression levels of these genes did not change. In DCD and DBD kidneys, early apoptosis increased after CI.
  
  
  CONCLUSIONS
  The gene expression profile in DBD kidneys represents an inflammatory and injury response to brain death. In contrast, DCD kidneys show only mild up-regulation of inflammatory and injury genes. These results may imply why delayed graft function in DCD kidneys does not have the deleterious effect it has on DBD kidneys.
authors.affiliation: Department of Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands.
authors.forename: Tanja C
authors.initials: TC
authors.lastname: Saat
authors.forename: Denis
authors.initials: D
authors.lastname: Susa
authors.forename: Henk P
authors.initials: HP
authors.lastname: Roest
authors.forename: Niels F M
authors.initials: NF
authors.lastname: Kok
authors.forename: Sandra
authors.initials: S
authors.lastname: van den Engel
authors.forename: Jan N M
authors.initials: JN
authors.lastname: Ijzermans
authors.forename: Ron W F
authors.initials: RW
authors.lastname: de Bruin
mesh_terms: D058186:Acute Kidney Injury / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001926:Brain Death / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050377:Cold Ischemia; D019610:Cytoprotection; D051799:Delayed Graft Function / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers; D007249:Inflammation / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D023421:Models, Animal; D009926:Organ Preservation; D051381:Rats; D011914:Rats, Inbred BN; D012307:Risk Factors; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D005819:Genetic Markers; D018836:Inflammation Mediators