Effect of donor JNK signal transduction inhibition on transplant outcome in brain dead rat model.

Renal grafts from brain-dead donors compared to living donors have a significantly shortened survival time due to heightened renal immunogenicity. The influence of pretreatment with a JNK signal transduction inhibitor on ischemia-reperfusion injury was examined in a renal transplant model using donors from a standardized rat model of brain death. Donors were treated immediately after induction of brain death with a JNK signal transduction inhibitor or saline. Kidney grafts from experimental group and control groups (saline-treated brain dead or living donor grafts) were examined serially up to 7 days post transplantation by morphology, immunohistology, and real-time PCR. JNK inhibition reduced the intensity of ischemia-reperfusion injury and acute rejection compared to saline treated donors. Likewise, cellular infiltration, mRNA transcription of some representative proinflammatory mediators and MHC-II molecules in the grafts were diminished in the JNK-inhibited donors compared to saline controls. Lewis rats transplanted with kidneys from JNK inhibited, brain-dead BN donors survived significantly longer than rats transplanted with saline treated brain-dead donors. The JNK inhibitor pretreatment of brain dead rats improved donor kidney quality, and improved graft survival.