No abstract

The number of patients placed on kidney transplant waiting lists is rapidly increasing, resulting in a growing gap between organ demand and the availability of kidneys for transplantation. This organ shortage has forced medical professionals to utilize marginal kidneys from expanded criteria donors (ECD) to broaden the donor pool and shorten wait times for patients with end-stage renal disease. However, recipients of ECD kidney grafts tend to have worse outcomes compared to those receiving organs from standard criteria donors (SCD), specifically increased risks of delayed graft function (DGF) and primary nonfunction incidence. Thus, representative methods for graft-quality assessment are strongly needed, especially for ECDs. Currently, graft-quality evaluation is limited to interpreting the donor’s recent laboratory tests, clinical risk scores, the visual evaluation of the organ, and, in some cases, a biopsy and perfusion parameters. The last few years have seen the emergence of many new technologies designed to examine organ function, including new imaging techniques, transcriptomics, genomics, proteomics, metabolomics, lipidomics, and new solutions in organ perfusion, which has enabled a deeper understanding of the complex mechanisms associated with ischemia-reperfusion injury (IRI), inflammatory process, and graft rejection. This review summarizes and assesses the strengths and weaknesses of current conventional diagnostic methods and a wide range of new potential strategies (from the last five years) with respect to donor graft-quality assessment, the identification of IRI, perfusion control, and the prediction of DGF.

The limiting factor in conventional quality assessments of transplanted organs, namely the invasiveness of tissue sample collection, has prompted much research on the field of transplantology to focus on the development of alternative evaluation methods of organ quality. In the present project, we undertake the challenge to address the need for a new analytical solution for graft quality assessments by using a novel metabolomic diagnostic protocol based on low-invasive solid-phase microextraction. Solid-phase microextraction probes of ca. 0.2 mm coated with 4 mm long mixed-mode extraction phase were inserted into rabbit kidneys immediately following euthanasia and after 2, 4, 6, and 21 h of preservation. Liquid chromatography-mass spectrometry analysis of the extracts was performed with the use of a reversed phase column and a Q-Exactive Focus mass spectrometer operated in positive ionization mode. Statistical analysis of significantly changing compounds revealed metabolic profile changes in kidneys induced by ischemia and oxidative stress as a function of the duration of cold storage.The most pronounced alterations were reflected in levels of essential amino acids and purine nucleosides. Our findings demonstrate that the proposed approach may be successfully used to monitor changes in the metabolic profile of organs over time of preservation.