Hypothermic Machine Perfusion Modifies the Impact of Cold Ischemia Time on Kidney Transplant Outcomes: A...

Preservation strategies are critical for mitigating ischemia-reperfusion injury in kidney transplantation, particularly as the utilization of marginal grafts and prolonged cold ischemia times (CIT) increases. Although hypothermic machine perfusion (HMP) is increasingly used in kidney graft preservation, the comparative effectiveness of continuous HMP (cHMP), hybrid HMP-static cold storage (HMP-SCS), and static cold storage (SCS) alone remains incompletely defined. We evaluated the impact of preservation strategy, CIT, and HMP exposure on posttransplant outcomes.

We performed a retrospective analysis of 681 deceased-donor kidney transplants. Grafts were categorized as cHMP, hybrid HMP-SCS, or SCS alone. Outcomes analyzed overall outcomes as well as stratified the data by CIT (≤20 vs ≥20 hours). Primary outcomes included delayed graft function (DGF), primary nonfunction (PNF), graft and patient survival, serum creatinine, and length of stay (LOS). The effect of HMP exposure, defined as the proportion of total CIT spent on pump, was also evaluated.

Preservation groups differed substantially at baseline, with SCS grafts originating from younger donors with lower kidney donor profile index, lower terminal creatinine, and shorter CIT. In grafts with CIT ≤20 hours (n = 235), SCS was associated with superior graft and patient survival, likely reflecting preferential allocation of lower risk organs. DGF, PNF, renal function, and LOS were similar across preservation strategies. In grafts with CIT ≥20 hours (n = 446), hybrid HMP-SCS was associated with a lower incidence of DGF compared with cHMP (43.4% vs 55.8%, P = .021), while graft and patient survival, renal function, and LOS remained comparable across groups. Higher HMP exposure (≥60% of CIT) was associated with lower 12-month serum creatinine compared with lower exposure (1.36 vs 1.57 mg/dL, P ≤ .05), without differences in DGF, PNF, graft survival, patient survival, or LOS.

The impact of preservation strategy appears closely linked to ischemic burden. While SCS provides excellent outcomes in lower risk grafts with short CIT, the incorporation of HMP becomes increasingly relevant with prolonged ischemia. Hybrid HMP-SCS achieved outcomes comparable to cHMP and was associated with lower DGF in grafts with prolonged CIT, suggesting that uninterrupted machine perfusion may not be necessary to realize clinical benefit. However, greater HMP exposure was associated with improved 12-month renal function, indicating that perfusion duration may still influence graft recovery. Prospective studies are needed to define the optimal timing and duration of machine perfusion and to determine the minimum effective HMP dose in partially perfused kidney grafts.