Prolonged ex-vivo normothermic kidney perfusion: The impact of perfusate composition

Abstract

Normothermic machine perfusion (NMP) of donor kidneys provides the opportunity for improved graft preservation and objective pre-transplant ex-vivo organ assessment. Currently, a multitude of perfusion solutions exist for renal NMP. This study aimed to evaluate four different perfusion solutions side-by-side and determine the influence of different perfusate compositions on measured renal perfusion parameters. Porcine kidneys and blood were obtained from a slaughterhouse. Kidneys underwent NMP at 37°C for 7 hours, with 4 different perfusion solutions (n = 5 per group). Group 1 consisted of red blood cells (RBCs) and a perfusion solution based on Williams’ Medium E. Group 2 consisted of RBCs, albumin and a balanced electrolyte composition. Group 3 contained RBCs and a medium based on a British clinical NMP solution. Group 4 contained RBCs and a medium used in 24-hour perfusion experiments. NMP flow patterns for solutions 1 and 2 were similar, solutions 3 and 4 showed lower but more stable flow rates. Thiobarbituric acid reactive substances were significantly higher in solution 1 and 4 compared to the other groups. Levels of injury marker N-acetyl-β-D glucosaminidase were significantly lower in solution 2 in comparison with solution 3 and 4. This study illustrates that the perfusate composition during NMP significantly impacts the measured perfusion and injury parameters and thus affects the interpretation of potential viability markers. Further research is required to investigate the individual influences of principal perfusate components to determine the most optimal conditions during NMP and eventually develop universal organ assessment criteria.

Perfusate Composition and Duration of Ex-Vivo Normothermic Perfusion in Kidney Transplantation: A Systematic Review

“…Few studies to date have conducted head-to-head comparisons of perfusates for EVNP. A recent publication from Pool et al, however, compared four different perfusates during 7-hour EVNP of porcine kidney in a DCD model ( 36 ). While all four perfusates demonstrated feasibility, there were apparent differences between electrolyte levels, renal function parameters, and injury markers in the four groups.…”

Prolonged Controlled Oxygenated Rewarming Improves Immediate Tubular Function and Energetic Recovery of Porcine Kidneys During Normothermic Machine Perfusion

“…The machine perfusion setup was similar to previously described setups by our group. 18 , 19 The perfusion circuit consisted of a pump unit and centrifugal pump (cirQlife, XVIVO, Göteborg, Sweden), oxygenator (Hilite 800 LT, Medos Medizintechnik AG), LifePort organ chamber (Organ Recovery Systems), and thermal unit (Kidney Assist, XVIVO, Göteborg, Sweden). Pressure was measured at the distal end of the straight cannula (TruWave disposable pressure transducer, Edwards Lifesciences, Irvine, CA), flow was monitored using an ultrasonic clamp-on flow probe (Transonic Systems Europe B.V., Elsloo, the Netherlands), and temperature was monitored using a temperature sensor (Heraeus Nexensos PT100 Surface Sensor [W-SZK], Heraeus Nexensos GmbH, Kleinostheim, Germany), which was positioned underneath the kidney close to the venous outflow.…”

Ex-vivo Kidney Machine Perfusion: Therapeutic Potential

“…Moreover, proteomics analysis showed decreased damage-associated molecular patterns, angiotensinogen levels, and enhanced levels of enzymes involved in kidney metabolism, perfused with urine recirculation (81). Pool et al recently demonstrated that perfusate composition also significantly impact kidney injury and perfusion parameters during prolonged NMP (83). Basile et al observed stable perfusion parameters and no evidence of damage during 72 h of NMP, revealing that even several days of perfusion could be feasible (79).…”