The Effects of 6-Chromanol SUL-138 during Hypothermic Machine Perfusion on Porcine Deceased Donor Kidneys

L Annick Van Furth,Guido Krenning,Koen D W Hendriks,Pieter C Vogelaar,Leonie H Venema,Henri G D Leuvenink

doi:10.3390/transplantology2030031

L Annick Van Furth, Guido Krenning + Show 4 more

Open Access

https://doi.org/10.3390/transplantology2030031

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Abstract

Diminishing ischemia-reperfusion injury (IRI) by improving kidney preservation techniques offers great beneficial value for kidney transplant recipients. Mitochondria play an important role in the pathogenesis of IRI and are therefore interesting targets for pharmacological interventions. Hypothermic machine perfusion (HMP), as a preservation strategy, offers the possibility to provide mitochondrial–targeted therapies. This study focuses on the addition of a mitochondrial protective agent SUL—138 during HMP and assesses its effect on kidney function and injury during normothermic reperfusion. In this case, 30 min of warm ischemia was applied to porcine slaughterhouse kidneys before 24 h of non–oxygenated HMP with or without the addition of SUL—138. Functional assessment was performed by 4 h normothermic autologous blood reperfusion. No differences in renal function or perfusion parameters were found between both groups. ATP levels were lower after 30 min of warm ischemia in the SUL–138 group (n.s, p = 0.067) but restored significantly during 24 h of HMP in combination with SUL—138. Aspartate aminotransferase (ASAT) levels were significantly lower for the SUL—138 group. SUL—138 does not influence renal function in this model. Restoration of ATP levels during 24 h of HMP with the addition of SUL in combination with lower ASAT levels could be an indication of improved mitochondrial function.

Highlights

10% of the global need for donor organs is met [1]. This shortage has led to the use of sub–optimal quality organs donated from expanded criteria donors (ECD) and donation after circulatory death (DCD) donors [2]
Kidneys donated from DCD donors are more susceptible to ischemia-reperfusion injury (IRI) [3] than those donated from brain death (DBD) donors, and this is reflected by higher incidences of delayed graft function (DGF) [4,5,6]
To resemble potential clinical application, we explored the effect of SUL—138 during 24 h Hypothermic machine perfusion (HMP) of porcine DCD kidneys followed by assessment of kidney function in a normothermic reperfusion model

Summary

Introduction

10% of the global need for donor organs is met [1]. This shortage has led to the use of sub–optimal quality organs donated from expanded criteria donors (ECD) and donation after circulatory death (DCD) donors [2]. Kidneys donated from DCD donors are more susceptible to ischemia-reperfusion injury (IRI) [3] than those donated from brain death (DBD) donors, and this is reflected by higher incidences of delayed graft function (DGF) [4,5,6]. DGF has far—reaching consequences for the recipients of these kidneys since it requires a compulsory return of the patients to undergo haemodialysis until recovery of kidney function. The chance of acute cellular rejection and poorer long—term outcomes increases [7,8]

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