24 Cold Ischemia Time Alone Does Not Affect Graft Outcomes: A Big Data Analysis of UK Kidney Transplant Registry - CITGO Study

Abstract Background This study investigated the combined impact of cold ischemia time (CIT), donor risk index (DRI), HLA-mismatch, and donor type on kidney graft survival using data UK Transplant Registry Data. Methods A retrospective cohort study of 35,627 adult deceased-donor-kidney-transplant recipients (2000-2020) was conducted. Graft survival was analyzed using Kaplan-Meier curves and multivariable Cox proportional hazards models. A composite-risk-score was developed to stratify recipients. Results Median follow-up was 6.8 years (IQR: 3.2-11.5). Longer-CIT (HR 1.03 per hour, 95% CI 1.02-1.04, P<0.001), higher DRI (HR 1.45 per unit, 95% CI 1.38-1.52, P<0.001), greater HLA mismatch (HR 1.45 for ≥3 mismatches vs. 0, 95% CI 1.34-1.57, P<0.001), and donation after circulatory death (DCD) donor type (HR 1.28, 95% CI 1.20-1.36, P<0.001) were independently associated with increased risk of graft failure. Significant interactions were observed between CIT and DRI (P<0.001), CIT and HLA-mismatch (P=0.003), and DRI and HLA mismatch (P=0.016). The high-risk group had a 2.68-fold increased risk of graft failure (95% CI 2.44-2.95, P<0.001) compared to the low-risk group. Prolonged CIT (≥18 hours) had a greater impact on graft survival in DCD than in DBD-transplants (HR 1.51, 95% CI 1.39-1.64 vs. HR 1.19, 95% CI 1.12-1.27, both P<0.001). Conclusion This study demonstrates significant interactive effects of CIT, DRI, HLA-mismatch, and donor type on kidney graft survival, with more pronounced impacts in DCD-transplants. The composite risk score may aid in risk stratification and decision-making in kidney transplantation, highlighting the importance of considering multiple factors and their interactions in optimizing graft allocation and post-transplant care.