Comparative Analysis of Outcomes and Perfusate Proteomics from a High-Volume U.S. Center

Purpose: Hypothermic oxygenated perfusion (HOPE) is an emerging preservation method in the United States with growing evidence of improved kidney transplant (KT) outcomes, though the underlying mechanisms remain unclear.
Methods: Adult deceased donor KT performed betwen 12/1/2023-7/31/2025 at a single center were categorized in three groups by preservation methods—HOPE, static cold storage (SCS), or hypothermic non-oxygenated perfusion (HMP). The primary outcome was 6-month estimated glomerular filtration rate (eGFR), with subgroup analysis of donation after circulatory death (DCD). Perfusate (HOPE, HMP) or effluent (SCS) from expanded-criteria KT (n=30) was analyzed using proteomics. Differentially expressed proteins (DEP; p<0.05, FDR<0.05) underwent KEGG and GO enrichment analysis. Continuous variables were compared using Wilcoxon rank-sum and categorical variables by chi-square tests.
Results: Among 364 KT, 67 (18.4%) used HOPE, 173 (47.5%) SCS, and 124 (34.1%) HMP. Differences in donor characteristics included median donor age, KDPI, and proportion of DCD donors (all p<0.001). HOPE kidneys had a median total cold preservation time of 29.7hrs [24.9-36.7] compared to SCS (18.3hrs [15.6-21.5]) and HMP (20.2hrs [17.3-23.3], p<0.001). At 6-month, median eGFR was comparable across groups. In DCD-KT alone, HOPE kidneys had significantly higher 6-month eGFR than HMP (p=0.02). Proteomic analysis of perfusate identified 1086 total proteins, with 74 DEP and 46 uniquely downregulated proteins in HOPE, including proteins associated with ischemia-reperfusion injury (IRI) response such as FAS, heat-shock protein B6, and S100 proteins. Enrichment analyses revealed multiple pathways associated with IRI and metabolism, with downregulated DEP in HOPE, including regulation of ferroptosis, reactive oxygen species response, and metabolic processes such as glycolysis, carbohydrate catabolism, and unsaturated fatty acid metabolism (all p<0.05, Fig 1).
Conclusions: In this first large U.S. cohort, HOPE kidneys had improved 6-month eGFR relative to HMP and were comparable to SCS, with greatest benefit seen in DCD-KT. HOPE perfusate demonstrated downregulation of IRI-related proteins, suggesting reduced cellular stress that may contribute to improved graft function.