Canine kidney preservation models have historically used autotransplants to avoid the complications of rejection, although clinically all transplants are allografts. This study investigated the effects of preservation time and method on early kidney function in a canine allograft vs. autograft model. Kidneys were harvested from beagles, preserved by cold storage (CS) in
UW solution for 0, 24 or 72 h, or by machine perfusion (MP) with Belzer MPS for 72 h. In some experiments 45 min of
warm ischemia (WI) was performed in situ before harvest. Allograft recipients received
steroid immunosuppression. Kidney function was assessed by serum
creatinine and survival for 7 days. Allografts preserved for 0 and 24 h performed as well as autografts. Allografts preserved for 72 h by either CS or MP had a higher incidence of primary nonfunction (PNF) compared with autografts, as determined by survival (50% vs. 100%, p < 0.003). Primary nonfunction kidneys had
thrombotic microangiopathy, vascular and peritubular capillary binding of
IgM and
complement C4d, and evidence of circulating donor-specific
antibodies; all consistent with humoral rejection. These responses were dependent on
hypothermia time and were not attributable to
ischemia, immunosuppression, preservation
solution, or cellular rejection. In conclusion, prolonged
hypothermia can cause PNF in allografts owing to acute humoral rejection.