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

BACKGROUND: 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. MATERIALS AND METHODS: 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-1ß 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. RESULTS: 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-1ß 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. CONCLUSION: 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.

Histological evaluation of ischemic alterations in donors after cardiac death: A useful tool to predict post-transplant renal function.

Kidneys retrieved from donors after cardiac death (DCD) pose significant challenges from a clinical and technical point of view, undergoing a variable degree of ischemia-reperfusion injury. At present, the utilization of kidneys is assessed according to the Karpinski score, which does not take into account the ischemic insult and does not predict the functional recovery of the organ once transplanted. Therefore, the correlation between biopsy results and post-transplant graft function is still debated. In this study we examined kidney biopsies from DCD donors; we calculated the Karpinski score and subsequently identified and quantified the ischemic lesions in the glomerular, interstitial, and tubular compartments. These same lesions were quantified in kidney biopsies from donors after brain death (DBD) in a case-control analysis. The collected data were correlated with the clinical data of the donors and the post-transplant follow-up. Proximal tubule alterations are crucial in ischemia-reperfusion damage, showing precise histological alterations, which are more frequent in DCD than in DBD donors and are statistically correlated with functional recovery of the organ. Quantification of ischemic tubular lesions in biopsies of kidneys from DCD donors is a useful tool for predicting post-transplant renal function and a valid parameter for assessing the quality of the graft.

Ureteric complications in recipients of kidneys from donation after circulatory death donors.

A large increase in the use of kidneys from donation after circulatory death (DCD) donors prompted us to examine the impact of donor type on the incidence of ureteric complications (UCs; ureteric stenosis, urinary leak) after kidney transplantation. We studied 1072 consecutive kidney transplants (DCD n=494, live donor [LD] n=273, donation after brain death [DBD] n=305) performed during 2008-2014. Overall, there was a low incidence of UCs after kidney transplantation (3.5%). Despite a trend toward higher incidence of UCs in DCD (n=22, 4.5%) compared to LD (n=10, 3.7%) and DBD (n=5, 1.6%) kidney transplants, donor type was not a significant risk factor for UCs in multivariate analysis (DCD vs DBD HR: 2.33, 95% CI: 0.77-7.03, P=.13). There was no association between the incidence of UCs and donor, recipient, or transplant-related characteristics. Management involved surgical reconstruction in the majority of cases, with restenosis in 2.7% requiring re-operation. No grafts were lost secondary to UCs. Despite a significant increase in the number of kidney transplants from DCD donors, the incidence of UCs remains low. When ureteric complications do occur, they can be treated successfully with surgical reconstruction with no adverse effect on graft or patient survival.