Abstract

Ischemia-reperfusion injury (IRI) occurring after renal transplantation is a complex biochemical process that can be monitored by specific biomarkers. The roles of those are not yet fully elucidated. The aim of this study was to analyze the concentrations of endothelins (ET-1, ET-2, and ET-3), interleukin-18 (IL-18), and neutrophil gelatinase-associated lipocalin (NGAL) during the reperfusion of human kidneys grafted from brain dead donors and later transplanted. The study group (n = 44) was analyzed according to the method of kidney storage: Group 1 underwent hypothermic machine perfusion (HMP) in the LifePort perfusion pump (n = 22), and Group 2 underwent static cold storage (SCS) (n = 22). The analysis of kidney function was performed daily during the first seven days after transplantation. The kidneys in Group 1 were characterized by higher absolute concentrations of ET-1, IL-18, and NGAL, as well as a lower concentration of ET-2 (p = 0.017) and ET-3. The relative increase of ET-1 (p = 0.033), ET-2, and ET-3 during reperfusion was lower in this group, while the relative decrease of NGAL was higher. Group 1 was also characterized by significant decrease of IL-18 (p = 0.026) and a tendency for better kidney function based on the higher total diuresis, higher glomerular filtration rate (GFR), higher potassium level, lower serum creatinine, and lower urea concentration during the seven-day postoperative observation period. The long-term beneficial impact of hypothermic machine perfusion on the outcome of transplanted kidneys may rely on the early modified proceedings and intensity of ischemia-reperfusion injury reflected by the dynamics of the concentrations of examined biomarkers.

Highlights

  • The influence of donor condition on outcome is multifactorial [1], but organs with extended-criteria are known to be more susceptible to ischemia-reperfusion injury (IRI), which is a major determinant of delayed graft function (DGF) [2,3,4]

  • (∆) were statistically insignificant, but we noticed a tendency towards greater ∆ increases of ET-1, ET-2, and ET-3 in Group 2

  • The results of our study showed that kidneys in the hypothermic machine perfusion compared with static cold storage were characterized by higher absolute concentrations of ET-1, IL-18, and neutrophil gelatinase-associated lipocalin (NGAL), as well as lower concentrations of ET-2 and ET-3

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Summary

Introduction

Kidney transplantation (KTx) is the only curative treatment option for patients suffering from end-stage renal failure. The growing imbalance between the number of surgical procedures and patients on the transplant waiting lists remains a major concern in all countries. Despite the increasing use of donation after circulatory death (DCD) and extended criteria donor (ECD), overall patient and allograft survival rates are improving. The influence of donor condition on outcome is multifactorial [1], but organs with extended-criteria are known to be more susceptible to ischemia-reperfusion injury (IRI), which is a major determinant of delayed graft function (DGF) [2,3,4]. IRI consists of two phases: ischemia, when the blood flow is interrupted for a period of time separating organ procurement from

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