Prolonged Cold Ischemia Time Offsets the Benefit of Human Leukocyte Antigen Matching in Deceased Donor Kidney Transplant

Background: The consequences of prolonging cold ischemia time (CIT) to facilitate HLA matching in kidney transplantation are not known. Methods: Patients with a history of kidney transplant in the United States (2000-2016) with 0 HLA mismatch (MM) were categorized based on CIT (< 10; 10 to < 15; 15 to < 20; 20 to < 25; 25 to < 30; and ≥ 30 hours). Time to graft loss was compared for each CIT category to a reference group of individuals with > 0 HLA MM and short CIT (< 10 hours) using a multivariable Cox proportional hazards model. Results: The adjusted risk of graft failure was significantly lower for 0 HLA MM with the shortest CIT compared to the reference group (hazard ratio, 0.82; 95% confidence interval, 0.72-0.94), and this survival advantage persisted to a threshold of < 20 hours of CIT. No survival advantage was observed for the 0 HLA MM group once CIT was > 20 hours. This trend persisted after excluding highly sensitized recipients (panel reactive antibody > 98%) where shipping of organs occurs to achieve more equitable access to organs rather than optimize HLA match. Conclusions: CIT > 20 hours offsets the benefit of 0 HLA MM in kidney transplantation. This may have implications in organ shipping to facilitate immunologic match.