Influence of donor brain death on chronic rejection of renal transplants in rats.
The clinical observation that the results of kidney grafts from living donors (LD), regardless of relationship with the host, are consistently superior to those of cadavers suggests an effect of brain death (BD) on organ quality and function. This condition triggers a series of nonspecific inflammatory events that increase the intensity of the acute immunologic host responses after transplantation (Tx). Herein are examined the influences of this central injury on late changes in renal transplants in rats. A standardized model of BD was used. Groups included both allografts and isografts from normotensive brain dead donors and anesthetized LD. Renal function was determined every 4 wk after Tx, at which time representative grafts were examined by morphology and by reverse transcriptase-PCR. Long-term survival of brain-dead donor transplants was significantly less than LD grafts. Proteinuria was significantly elevated in recipients of grafts from BD donors versus LD controls as early as 6 wk postoperatively and increased progressively through the 52-wk follow up. These kidneys also showed consistently more intense and progressive deterioration in renal morphology. Changes in isografts from brain-dead donors were less marked and developed at a slower tempo than in allografts but were always greater than those in controls. The transcription of cytokines was significantly increased in all brain-dead donor grafts. Donor BD accelerates the progression of long-term changes associated with kidney Tx and is an important risk factor for chronic rejection. These results explain in part the clinically noted difference in long-term function between organs from cadaver and living sources.
Pratschke
Johann
J
Surgical Research Laboratory, Harvard Medical School, Boston, Massachusetts.|Department of Pathology, Harvard Medical School, Boston, Massachusetts.
Wilhelm
Markus J
MJ
Surgical Research Laboratory, Harvard Medical School, Boston, Massachusetts.
Laskowski
Igor
I
Surgical Research Laboratory, Harvard Medical School, Boston, Massachusetts.
Kusaka
Mamoru
M
Surgical Research Laboratory, Harvard Medical School, Boston, Massachusetts.
Beato
Francisca
F
Surgical Research Laboratory, Harvard Medical School, Boston, Massachusetts.
Tullius
Stefan G
SG
Department of Surgery, Humboldt University, Charité-Virchow Clinic, Berlin, Germany.
Neuhaus
Peter
P
Department of Surgery, Humboldt University, Charité-Virchow Clinic, Berlin, Germany.
Hancock
Wayne W
WW
Department of Pathology, Harvard Medical School, Boston, Massachusetts.|Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts.
Tilney
Nicholas L
NL
Surgical Research Laboratory, Harvard Medical School, Boston, Massachusetts.|Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts.
D000818:Animals; D001926:Brain Death / Q000503:physiopathology*; D002908:Chronic Disease; D006084:Graft Rejection / Q000209:etiology*; D006085:Graft Survival; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014019:Tissue Donors
D012333:RNA, Messenger