The effect on early renal function of various dynamic preservation strategies in a preclinical pig ischemia–reperfusion autotransplant model

Abstract

The aims of this study were to determine the most optimal timing to start machine perfusion during kidney preservation to improve early graft function and to evaluate the impact of temperature and oxygen supply during machine perfusion in a porcine ischemia-reperfusion autotransplant model. The left kidney of an approximately 40-kg female Belgian Landrace pig was exposed to 30 minutes of warm ischemia via vascular clamping and randomized to 1 of 6 study groups: (1) 22-hour static cold storage (SCS) (n = 6), (2) 22-hour hypothermic machine perfusion (HMP) (n = 6), (3) 22-hour oxygenated HMP (n = 7), (4) 20-hour HMP plus 2-hour normothermic perfusion (NP) (n = 6), (5) 20-hour SCS plus 2-hour oxygenated HMP (n = 7), and (6) 20-hour SCS plus 2-hour NP (n = 6). Graft recovery measured by serum creatinine level was significantly faster for continuous HMP preservation strategies compared with SCS alone and for all end-ischemic strategies. The active oxygenated 22-hour HMP group demonstrated a significantly faster recovery from early graft function compared with the 22-hour nonactive oxygenated HMP group. Active oxygenation was also found to be an important modulator of a faster increase in renal flow during HMP preservation. Continuous oxygenated HMP applied from the time of kidney procurement until transplant might be the best preservation strategy to improve early graft function.

Hypothermic Oxygenated New Machine Perfusion System in Liver and Kidney Transplantation of Extended Criteria Donors:First Italian Clinical Trial

“…Moreover, recipients in HOPE-K with DGF had undergone perfusion treatment for less than two hours, as compared to non-DGF patients which actually underwent perfusion treatment for more than 2 hours. Therefore, based on our experience, we suggest that kidney perfusion should last at least two hours; this treatment time could be possibly longer, as suggested by a pre-clinical study 27 .…”

Brief O2 uploading during continuous hypothermic machine perfusion is simple yet effective oxygenation method to improve initial kidney function in a porcine autotransplant model

“…Anesthetic and surgical protocols were followed as described previously. 6,7 The left kidney was removed after 30 minutes of warm ischemia induced by vascular clamping of the renal vessels and subsequently flushed with 200 mL of Kidney Perfusion Solution (KPS-1, Organ Recovery Systems, Diegem, Belgium). The kidney was randomized to one of the following preservation strategies: (1) 2-hour oxygenated HMP (90% oxygen) (HMPO 2 ) + 20-hour HMP with no additional oxygen (n = 6) or (2) 20-hour HMP followed by 2-hour HMPO 2 (n = 5).…”

“…We recognize that there are a number of limitations inherent to this porcine autotransplant. 6 The use of historical control groups might have introduced a relevant bias due to slightly shorter anastomosis time in the experimental study groups compared with one of the historical groups but was recommended by the ethics committee to reduce animal numbers and suffering. However, because total preservation time was comparable between all study groups we do not expect to have an important influence on the outcome measures.…”

“…animal models: porcine, autotransplantation, ischemia-reperfusion injury (IRI), kidney (allograft) function/dysfunction, kidney transplantation/nephrology, organ perfusion and preservation, organ procurement and allocation, translational research/science heat exchanger as described previously. 6,7 The KPS-1 solution was pumped through the kidney at a pressure of 30 mm Hg. Carbogen (95% O 2 /5% CO 2 ) and not 100% oxygen was used for oxygen supplementation at 90% in the experimental groups to have identical conditions as compared with the historical oxygenated group.…”

Kidney Perfusion as an Organ Quality Assessment Tool—Are We Counting Our Chickens Before They Have Hatched?

“…The same group showed that kidney assessment during warm perfusion might lead to transplantation of initially discarded DCD kidneys [49]. Extending normothermic perfusion to longer periods (2 to 8 hours) has been explored in pig studies [50][51][52][53][54]. Kidneys not suitable for transplantation have been normothermically perfused for 24 hours, making use of urine recirculation, though not transplanted [55].…”