Normothermic Ex-vivo Kidney Perfusion Improves Function of Marginal Renal Grafts that were Subjected to Prolonged Ischemia Prior to Preservation

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BackgroundNormothermic ex-vivo kidney perfusion (NEVKP) is an emerging technique for renal graft preservation. We investigated whether NEVKP could promote improved marginal graft function compared to cold storage in a model of donation after cardiac death.MethodsKidneys from 30kg Yorkshire pigs were removed following 30, 60, 90, or 120 minutes of warm ischemia (WI). These grafts were then preserved in either cold histidine-tryptophan-ketoglutarate solution (CS) or subjected to pressure-controlled NEVKP for 8 hours prior to heterotopic autotransplantation.ResultsProlonging WI time prior to kidney retrieval and subsequent storage in CS resulted in grafts that demonstrated incremental posttransplant increases in serum creatinine with grafts subjected to 120min of WI having persistent elevation (POD7: 13.45±3.50mg/dl vs baseline: 1.1±0.33mg/dl p<0.01, n=4). During NEVKP perfusion, 120min WI grafts cleared lactate from perfusion solution (0hr: 10.48±0.93mmol/L vs 7hr: 1.48±0.85mmol/L, p<0.01, n=5), had decreasing intra-renal resistance (0hr: 2.26±0.9mmHg/mL/min vs 7hr: 0.37±0.6mmHg/mL/min, p<0.01), and continuous urine production. Posttransplantation, 120min WI grafts with NEVKP, compared to CS, demonstrated significantly decreased serum creatinine peak values (POD4: 12.62±2.34mg/dl vs POD5: 18.95±1.11mg/dL, p=0.001) and higher creatinine clearance (POD4: 6.61±4.03mL/min vs 0.35±0.30mL/min, p=0.02 and POD7: 26.31±11.54mL/min vs 9.78±4.6mL/min, p=0.03). On POD7, serum creatinine returned to baseline values in the NEVKP group (POD7: 4.88±5.57mg/dL vs baseline: 1.02±0.16mg/dL, p=0.16) but not the CS group (POD7: 13.45±3.50mg/dl vs baseline: 1.1±0.33mg/dl p<0.01, n=4). Histology from 120min WI NEVKP grafts at POD7 demonstrated decreased tubular injury scores compared to cold CS grafts (1.8+/-0.8 vs. 3.0+/-0.0, p=0.03) as assessed by a blinded pathologist.ConclusionKidney grafts subjected to 120min of WI before retrieval showed significant improvement in function following 8hrs of continuous pressure-controlled NEVKP compared to CS. This suggests NEVKP could be utilized to expand the donor pool through the consideration of extreme marginal grafts for transplantation.

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