Cold Preflush of Porcine Kidney Grafts Prior to Normothermic Machine Perfusion Aggravates Ischemia Reperfusion Injury

André Stollenwerk,Benedict M Doorschodt,Rolf Rossaint,René H Tolba,Christian Bleilevens,Peter Boor,Gregor Fabry,Aaron Elliott,Tim Grzanna

doi:10.1038/s41598-019-50101-7

André Stollenwerk, Benedict M Doorschodt + Show 7 more

Open Access

https://doi.org/10.1038/s41598-019-50101-7

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Journal: Scientific Reports	Publication Date: Sep 25, 2019
Citations: 11	License type: open-access

Affiliation: RWTH Aachen University

Abstract

Normothermic machine perfusion (NMP) of kidney grafts is a promising new preservation method to improve graft quality and clinical outcome. Routinely, kidneys are washed out of blood remnants and cooled using organ preservation solutions prior to NMP. Here we assessed the effect of cold preflush compared to direct NMP. After 30 min of warm ischemia, porcine kidneys were either preflushed with cold histidine-tryptophan-ketoglutarate solution (PFNMP group) prior to NMP or directly subjected to NMP (DNMP group) using a blood/buffer solution. NMP was performed at a perfusion pressure of 75 mmHg for 6 h. Functional parameters were assessed as well as histopathological and biochemical analyses. Renal function as expressed by creatinine clearance, fractional excretion of sodium and total output of urine was inferior in PFNMP. Urine protein and neutrophil gelatinase-associated lipocalin (NGAL) concentrations as markers for kidney damage were significantly higher in the PFNMP group. Additionally, increased osmotic nephropathy was found after PFNMP. This study demonstrated that cold preflush prior to NMP aggravates ischemia reperfusion injury in comparison to direct NMP of warm ischemia-damaged kidney grafts. With increasing use of NMP systems for kidneys and other organs, further research into graft flushing during retrieval is warranted.

Highlights

Renal blood flow was lower in the preflush before normothermic perfusion (PFNMP) group compared to the DNMP group at 1 and 2 h reperfusion (63 ± 4.7 vs. 141.6 ± 5.6 ml/min, p < 0.001 and 87 ± 7.4 vs. 169.4 ± 6.9 ml/min, p < 0.001 resp., Fig. 4A), while intrarenal resistance (IRR) showed a tendency to be higher in the PFNMP group during 6 h of reperfusion to the PFNMP group without reaching significance (Fig. 4B)
We investigated warm ischemia-damaged porcine kidneys, either preflushed with cold HTK solution (PFNMP group) or without preflush (DNMP group) prior to 6 h reperfusion using a normothermic machine perfusion (NMP) system
In comparison to the DNMP group, PFNMP kidneys gained more weight during reperfusion and histological samples showed a larger degree of osmotic nephropathy

Summary

Introduction

In order to further improve kidney graft quality, the effects of cold preflush should be further examined in the context of NMP. The only study describing direct machine perfusion without cold preflush reported greater ischemia reperfusion injury in kidneys flushed with cold preservation solution followed by CS than in the direct perfusion group[15]. The results indicated a trend towards lowered kidney function in the cold flush and storage group, the NMP time was limited to 145 min. We aimed to investigate the isolated effect of cold preflush without subsequent cold storage. We hypothesized that cold preflush before normothermic perfusion (PFNMP) aggravates kidney graft injury in comparison to normothermic perfusion directly after retrieval (DNMP). We aimed to compare the extent of ischemia reperfusion injury between both groups during 6 h of NMP

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