title: Early and late injury to renal transplants from non-heart-beating donors.
abstract: BACKGROUND
  The lack of adequate numbers of kidneys for transplantation has stimulated interest in the use of organs from non-heart-beating donors (NHBDs). The short- and long-term effects of this risk factor on kidney isografts and allografts were examined with a rat model.
  
  
  METHODS
  NHBDs were killed by ether overdose. Kidney isografts (male Lewis rats [LEW]-->LEW) were transplanted orthotopically into bilaterally nephrectomized recipients 15, 30, 45, and 90 min after asystole to determine short-term survival patterns, which were compared to those of rats bearing kidneys from living donors (LDs, 0 min). Isografts and allografts (Fisher 344 rats-->LEW) from 45-min and 105-min NHBDs and from LD controls were placed in additional recipients in which contralateral native nephrectomy was performed on day 10 to allow the injured graft to recover from its ischemic insult. Serum creatinine, proteinuria, and graft morphology were assessed serially over a 24-week follow-up period.
  
  
  RESULTS
  Early survival and renal dysfunction of isografted rats correlated with the interval of donor cardiac arrest before transplantation. Long-term survival of recipients of kidneys from LDs and between 45-min and 105-min NHBDs was also significantly different (100% vs. 87% vs. 37% at 24 weeks, respectively, P<0.03). Proteinuria increased progressively over time, proportionate to the period of donor asystole, and was associated with increasing cellular infiltration, tubular atrophy, and glomerulosclerosis in the grafts. The development of important functional and structural changes was intensified in NHBD allografts. LD allografts showed early changes of chronic rejection.
  
  
  CONCLUSIONS
  The results emphasize the continuum between an initial nonspecific, donor-associated renal injury and late functional and morphologic changes associated with the interval of donor cardiac arrest. These events are accelerated in NHBD allografts that experience the added insult of host alloreactivity.
authors.affiliation: Surgical Research Laboratory, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Laskowski
authors.forename: Johann
authors.initials: J
authors.lastname: Pratschke
authors.forename: Marcus M
authors.initials: MM
authors.lastname: Wilhelm
authors.forename: Martin
authors.initials: M
authors.lastname: Gasser
authors.forename: Dustin
authors.initials: D
authors.lastname: Paz
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Hancock
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Tilney
mesh_terms: D000818:Animals; D001284:Atrophy; D002908:Chronic Disease; D005923:Glomerulosclerosis, Focal Segmental / Q000473:pathology; D006084:Graft Rejection / Q000473:pathology / Q000503:physiopathology; D006323:Heart Arrest; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology*; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000473:pathology; D019520:Living Donors; D008297:Male; D011507:Proteinuria / Q000652:urine; D051381:Rats; D011917:Rats, Inbred Lew; D016019:Survival Analysis; D014019:Tissue Donors; D014185:Transplantation, Isogeneic