Normothermic Ex-vivo Kidney Perfusion Improves Function of Marginal Renal Grafts that were Subjected to Prolonged Ischemia Prior to Preservation.
Peter Urbanellis1, Matyas Hamar1, Ivan Linares1, Dagmar Kollmann1, Sujani Ganesh1, Rohan John2, Paul Yip1, Istvan Mucsi1, Anand Ghanekar1, Darius Bagli3, Ana Konvalinka1, David Grant1, Lisa Robinson4, Markus Selzner1.
1Multi-Organ Transplantation Program, University Health Network, Toronto, ON, Canada; 2Laboratory Medicine and Pathobiology, University Health Network, Toronto, ON, Canada; 3Department of Surgery (Urology) and Physiology, The Hospital for Sick Children, Toronto, ON, Canada; 4Division of Nephrology, The Hospital for Sick Children, Toronto, ON, Canada
Background: Normothermic 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.
Methods: Kidneys 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.
Results: Prolonging 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.
Conclusion: Kidney 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.
