Transplantation/immunology
Lipid peroxidation products in machine perfusion of older donor kidneys

https://doi.org/10.1016/j.jss.2012.04.071Get rights and content

Abstract

Background

Owing to the shortage of donors, organs with an increased risk potential such as grafts recovered from expanded criteria donors are increasingly being used in transplants. Machine perfusion (MP) technology offers the possibility of determining the biomarkers in the perfusion solution so that conclusions might be drawn regarding the effectiveness of organ preservation and organ viability.

Methods

All kidneys from the MP arm of our multicenter, randomized, controlled trial of MP whose donors were aged 55 years or older were included in the present study. The biomarkers, total glutathione-S-transferase (GST), α-GST, and π-GST and markers for lipid peroxidation and cell decay were determined in the MP perfusate and correlated with the outcomes after kidney transplantation.

Results

A total of 111 machine perfused kidneys were included in the present study. The mean donor age was 64.1 ± 6.6 y. The average cold ischemic time was 13.8 ± 5.3 h. Total GST, α-GST, and lipid peroxidation markers were significantly elevated at the end of MP. However, according to the multivariate analysis, only the lipid peroxidation markers were independent predictors of delayed graft function after transplantation.

Conclusions

Our data suggest that routine determination of lipid peroxidation markers in the perfusate of expanded criteria donor kidneys can provide the opportunity to identify the kidneys that have sustained severe oxidative damage and should be excluded from transplantation. Additional analysis of a larger cohort with more primary nonfunction cases is needed to confirm these findings.

Introduction

Recently, as a part of a randomized, controlled study, our research group demonstrated the advantages of pulsatile machine perfusion (MP) compared with traditional cold storage of deceased donor kidneys [1]. MP led to a significant reduction in complications such as delayed graft function (DGF), primary nonfunction (PNF), and graft failure within 1 year. Because of the shortage of donors, organs with an increased risk potential such as allografts recovered from expanded criteria donors (ECDs) are being increasingly used for transplantation. Although MP is, to a considerable extent, successful with regard to organs of this type, the post-transplant complication rates after MP have remained greater than with non-ECD kidneys after static cold storage [2], [3], [4]. Taking into account the high physical and psychological strain placed on patients as a result of a failed transplant and the high costs associated with such a serious complication, criteria are being sought that will allow a pretransplant evaluation of kidney quality, so that organs at risk of a very poor outcome can be identified and excluded from transplantation. MP technology offers the possibility of determining biomarkers in the perfusion solution from which conclusions might be drawn regarding the effectiveness of organ preservation and organ viability. Prospective evidence was derived from our controlled trial that total glutathione-S-transferase (tGST), N-acetyl-β-d-glucosaminidase, and heart type fatty acid-binding protein measured during kidney MP could have a predictive value for post-transplant outcome [5]. tGST, N-acetyl-β-d-glucosaminidase, and heart type fatty acid-binding protein were independent predictors of delayed graft function but not of primary nonfunction and graft survival. Hence, we have concluded that none of these predictors should be recommended for excluding kidneys from transplantation [5].

To bring us closer to the aforementioned objective, a subgroup with an increased risk of post-transplant complications was studied from our prospective data set for the present analysis. In the present study, the MP perfusates of kidneys recovered from donors who were aged 55 years or older were examined. The isoenzymes α-GST, an indicator of damage to the proximal kidney tubules, and π-GST (pGST), an indicator of damage to the distal kidney regions, were both identified along with tGST. Lactate dehydrogenase, lactate, and lipid peroxidation products (LPOP) served as markers for cell and tissue decay.

Section snippets

Methods

All kidneys from the MP arm of our multicenter, randomized, controlled study of MP (Current Controlled Trials no. ISRCTN 83876362) whose donors were aged 55 years or older were included in the present study, provided that at least one of the two required perfusate samples had been collected. This age limit was selected as a modification of the ECD definition, in accordance with an existing trial proposal for the German Research Foundation (Deutsche Forschungsgemeinschaft). Detailed information

Results

A total of 111 machine perfused kidneys were included in the present study. The mean donor age was 64.1 ± 6.6 y. The age distribution is shown in Fig. 1. The average cold ischemic time (CIT) was 13.8 ± 5.3 h. A significant negative correlation was found between donor age and CIT (coefficient correlation −0.394, P < 0.001). After transplantation, 28 cases of DGF (25.2%) developed, including 2 cases of PNF (1.8%) and 8 cases of graft loss during the course of 1 y (7.2%). The concentrations of all

Discussion

In our analysis, of the six measured MP perfusate biomarkers, only LPOP was found to be a significant independent predictor for the occurrence of important complications after transplantation. The association we found between α-GST and tGST at the end of perfusion and the occurrence of DGF can at least be used as a general pretransplant risk assessment. It was, however, not decisive enough for an accurate prediction of the prospects of success of an individual kidney transplant. From these

Acknowledgments

This study was funded by Deutsche Forschungsgemeinschaft (grant DFG TR 811/1-1) and the Köln (Cologne) Fortune Program (University of Cologne Faculty of Medicine, Cologne, Germany). The authors are indebted to Andrea Elbers and Judith Stegemann for their excellent technical assistance.

References (22)

  • I. Jochmans et al.

    Machine perfusion versus cold storage for the preservation of kidneys donated after cardiac death

    Ann Surg

    (2010)
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