Changes in double-strand DNA breaks predict delayed graft function (DGF) in Japanese renal allograft recipients

Background Although delayed graft function (DGF) is a serious complication following kidney transplantation, a reliable and early diagnostic test is lacking to identify the grade of DGF. Methods We investigated changes in double-strand DNA breaks (DSBs), and factors related to DGF, such as ischemic times at transplantation and serum creatinine (sCr) levels. DSBs were detected by phospho-histone H2A.X (γ-H2AX) expression and cellular regeneration by Ki-67 before (0 h) and 1 h after allograft reperfusion (1 h) in each subject. Results The expression of γ-H2AX or Ki-67 at 0 h showed no difference between the living and deceased donors. γ-H2AX at 1 h decreased in the living donors, but increased in the deceased donors compared with that of 0 h( p = 0.017). Changes (Δ) in γ-H2AX between 0 and 1 h were different among subgroups, i.e., immediate function, slow graft function with dialysis 12% of Δγ-H2AX at 100% sensitivity and 88.2% specificity (ROC analysis, AUC: 0.922, p = 0.023). In a multivariate regression analysis, donor sCr and Δγ-H2AX were two main predictors of the grade of DGF ( p = 0.002). The expression of Ki-67 was very low at both 0 h and 1 h. Conclusion The combination of donor sCr and Δγ-H2AX from 0 to 1 h after reperfusion may predict severe DGF and PNF in the early phase.