IP-10, apoptotic genes, and calcineurin subtype messenger RNA kinetics occurring in rat renal isografts from brain-dead donors.
BACKGROUND
Brain death (BD) and following ischemia/reperfusion(I/R) injury has cardinal implications in kidney transplantation (Tx). We hypothesize that inflammation, apoptosis, and drug nephrotoxicity are central mechanisms leading to initial organ damage in transplantation from BD donors. In this study, the gene kinetics of a chemokine (IP-10), an apotosis-related gene, and of calcineurin (Cn) subtype were compared using kidney isografts from BD versus living donors.


METHODS
Donors were intubated and mechanically ventilated for 6 hours. Grafts were harvested 6 hours after BD, and at 1, 6, and 24 hours and 5 days after engraftment. Messenger RNA (mRNA) expression was assessed using real-time reverse transcriptase-polymerase chain reaction.


RESULTS
Gene expression of IP-10 was up-regulated only among BD donor kidneys, particularly following I/R injury. These changes recovered to baseline levels thereafter. Bcl-2 was suppressed within 6 hours of BD and 1 hour after engraftment. In contrast, Bax in kidneys from BD donors was significantly up-regulated at 6 hours after engraftment. These changes were minimal in the controls. Cn Aalpha and Abeta were decreased in kidneys from BD donors before and within 1 hour after engraftment. However, these differences became insignificant thereafter.


CONCLUSIONS
Marked up-regulation of IP-10 may predict the initial graft injury and the onset of delayed graft function. Apoptotic gene changes may lead kidney grafts to a preapoptotic condition and up-regulate renal toxicity caused by Cn inhibitors. This initial antigen-independent donor circumstance may be one risk factor for chronic rejection.
Kusaka
M
M
Department of Urology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. mkusaka@fujita-hu.ac.jp
Fukami
N
N
Sasaki
H
H
Higuchi
T
T
Ishikawa
K
K
Shiroki
R
R
Hoshinaga
K
K
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001926:Brain Death; D019703:Calcineurin / Q000145:classification / Q000235:genetics*; D054357:Chemokine CXCL10; D019743:Chemokines, CXC; D016207:Cytokines / Q000235:genetics*; D005786:Gene Expression Regulation; D016030:Kidney Transplantation / Q000502:physiology*; D007700:Kinetics; D019520:Living Donors; D023421:Models, Animal; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011917:Rats, Inbred Lew; D014185:Transplantation, Isogeneic
D054357:Chemokine CXCL10; D019743:Chemokines, CXC; C091326:Cxcl10 protein, rat; D016207:Cytokines; D012333:RNA, Messenger; D019703:Calcineurin