Effects of prolonged cold ischemia on the DCD kidney function and Inflammasome expression in rat kidney transplants

• Published in: Transplant immunology Vol. 74; p. 101511
• Main Authors: Wang, Xiao-Wen, Guo, Ren-De, Ma, Jian-Gong, Wang, Yi-Wei, Zou, Xun-feng
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2022
• Subjects: DCD kidney; Ferrous iron; L renal transplantation; NLRP3 Inflammasome; Prolonged cold storage; DCD kidney; NLRP3 Inflammasome; Ferrous iron; L renal transplantation; Prolonged cold storage
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2021.101511

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. 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. 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. 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. •Our data showed that prolonged cold storage of DCD kidney caused severe graft ischemia reperfusion injury in rat kidney transplant.•The NLRP3 -IL1β signal has been involved in cold-induced AKI in DCD kidneys.•Prolonged cold storage induced severe ischemia reperfusion injury in DCD kidney.