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Objectives:  We aimed to analyze the effect of cold ischemia time (CIT) on post-transplant graft function through mixed-effect model analysis to reduce the bias caused by paired mate kidneys.   Methods:  We reviewed all kidney transplantation records from 2015 to 2019 at our center. After applying the exclusion criteria, 561 cases were included for analysis. All donor characteristics, preservation and matching information, and recipient characteristics were collected. Transplant outcomes included delayed graft function (DGF) and estimated glomerular filtration rate (eGFR). Generalized linear mixed models were applied for analysis. We also explored potential effect modifiers, namely, donor death category, expanded criteria donors, and donor death causes.   Results:  Among the 561 cases, 79 DGF recipients developed DGF, and 15 recipients who died after surgery were excluded from the eGFR estimation. The median stable eGFR of the 546 recipients was 60.39 (47.63, 76.97) ml/min/1.73 m 2 . After adjusting for confounding covariates, CIT had a negative impact on DGF incidence [odds ratio = 1.149 (1.006, 1.313),  P  = 0.041]. In the evaluation of the impact on eGFR, the regression showed that CIT had no significant correlation with eGFR [β = −0.287 (−0.625, 0.051),  P  = 0.096]. When exploring potential effect modifiers, only the death category showed a significant interaction with CIT in the effect on eGFR ( P  interaction  = 0.027). In the donation after brain death (DBD) group, CIT had no significant effect on eGFR [β = 0.135 (−0.433, 0.702),  P  = 0.642]. In the donation after circulatory death/donation after brain death followed by circulatory death (DCD/DBCD) group, CIT had a significantly negative effect on eGFR [β= −0.700 (−1.196, −0.204),  P  = 0.006]. Compared to a CIT of 0–6 h, a CIT of 6–8 or 8–12 h did not decrease the post-transplant eGFR. CIT over 12 h (12–16 h or over 16 h) significantly decreased eGFR. With the increase in CIT, the regenerated eGFR worsened ( P  trend  = 0.011).   Conclusion:  Considering the effect of paired mate kidneys, the risk of DGF increased with prolonged CIT. The donor death category was an effect modifier between CIT and eGFR. Prolonged CIT did not reduce the eGFR level in recipients from DBDs but significantly decreased the eGFR in recipients from DCDs/DBCDs. This result indicates the potential biological interaction between CIT and donor death category.

frontiers in medicine

Donor Death Category Is an Effect Modifier Between Cold Ischemia Time and Post-transplant Graft Function in Deceased-Donor Kidney Transplant Recipients