%0 Journal Article
%T Effects of prolonged cold ischemia on the DCD kidney function and Inflammasome expression in rat kidney transplants.
%A Wang XW
%A Guo RD
%A Ma JG
%A Wang YW
%A Zou XF
%J Transpl Immunol
%V 74
%N 0
%D 10 2022
%M 35483644
%F 2.032
%R 10.1016/j.trim.2021.101511
%X Acute kidney injury (AKI) is the main reason for the bad outcome of the donation of circulatory death (DCD) kidney after transplantation. Prolonged cold storage (CS) is a risk factor for the occurrence of the delayed graft function in DCD kidney. The protein NLR-domain containing receptor 3 (NLRP3) plays a crucial role in renal ischemia reperfusion injury by triggering inflammasome formation. Herein, we investigated whether the NLRP3 signal participate in the CS-induced damage of DCD kidney in rat kidney transplantation models.<BR>DCD kidney and living donor (LD) kidney of SD rats were preserved in UW solution at 4 °C for 2 h or 18 h, and then transplanted into syngeneic recipient. Thus, the animals were randomly divided into 4 groups: 2-h LD group, 2-h DCD group, 18-h LD group and 18-h DCD group. The renal function and pathological changes were determined. The expressions of NLRP3 and inflammatory factor IL-1β were assessed. The concentration of ferrous iron (Fe2+) was analyzed both in kidneys and in the preservation solution. The renal morphological changes were examined by hematoxylin eosin staining.<BR>Our results showed that the levels of Cr and BUN were higher in 18-h LD group as compared to the 2-h LD group, which were remarkably increased in 18-h DCD group. The expression levels of NLRP3 and IL-1β were increased by 18-h CS compared to 2-h CS in both LD kidney and DCD kidney. In addition, the Fe2+ concentration has significantly increased in 18-h LD group than that in 2-h LD group, and the elevation of Fe2+ was more remarkable in DCD kidneys.<BR>In conclusion, our study demonstrated that prolonged hypothermic storage of DCD kidney deteriorated the graft function via the increased Fe2+ concentration, which was associated with the upregulation of NLRP3 expression.