Prediction of renal function upon reperfusion by ex situ controlled oxygenated rewarming

Abstract

BackgroundPost‐transplant function of suboptimal kidney grafts can be improved but not accurately predicted by hypothermic machine perfusion. Therefore, a new concept of ex situ pre‐implantation machine perfusion with controlled rewarming up to subnormothermic temperatures was developed and evaluated.Materials and methodsPorcine kidneys (n = 6/group) were retrieved before or 30 min after cardiac arrest of the donor and subjected to 18 h of static cold storage. In some cases, 90 min of machine‐controlled oxygenated rewarming (COR) was added thereafter. Functional integrity was evaluated in all kidneys by subsequent normothermic reperfusion in vitro. After supplementation of the preservation solution (Custodiol‐N solution + 5 g/L dextran 40) with 10 mg/dL creatinine, ex situ renal function was assessed by monitoring urine output, urinary creatinine and creatinine clearance at 20 °C. Functional integrity was evaluated in all kidneys by normothermic reperfusion.Results COR resulted in a more than twofold improvement of postreperfusion creatinine clearance, oxygen consumption and enzyme release upon reperfusion, when compared with static cold storage. Predictive discrimination between kidneys with good or impaired function upon reperfusion based on parameters during perfusion at 4 °C was only moderate. This improved significantly at 20 °C. Correlation with renal clearance upon reperfusion was weak for vascular resistance at 8° (r 2 = 0·2) and 20 °C (r 2 = 0·41). Best correlation was found for clearance measurements at 20° (r 2 = 0·81).ConclusionsReconditioning by controlled oxygenated rewarming up to 20 °C improves renal function after reperfusion and can be utilized to assess graft integrity of predamaged donor kidneys.

Defining the optimal duration for normothermic regional perfusion in the kidney donor: A porcine preclinical study

“…Our model could also be interesting to establish a proper comparison between the current investigations for preservation improvement such as normothermic preservation, either at the end of the preservation or for the whole duration, or slow rewarming. 63,64 Such preclinical evaluation could establish their true benefits and uncover their potential additivity.…”

Role of temperature in reconditioning and evaluation of cold preserved kidney and liver grafts

“…In the kidney, functional data during perfusion at 20 °C significantly outweighed the weaker predictive power of markers obtained during hypothermic perfusion [ 63 ▪ ] and showed very well correlations with ulterior renal function upon warm reperfusion.…”

Opportunities for Therapeutic Intervention During Machine Perfusion

“…Similarly, an experimental study of NMP on DCD rat hearts demonstrated beneficial effects on recovery of electrical activity and contractility of the myocardial tissue [29]. Controlled oxygenated rewarming (COR) technique combines 30 minutes HMP, 30 minutes slow warming to 20° C, and then 30 minutes of SNMP, and has been applied after similar periods of SCS to both porcine livers and kidneys procured after cardiac death [5, 30]. In simulated reperfusion models, COR kidneys showed better creatinine clearance, decreased expression of inflammatory molecules, decrease endothelial cell activation, and improved tubular cell integrity compared to untreated kidneys.…”