Abstract
BackgroundKidney transplantation (KTx) is the best therapeutic approach for chronic kidney diseases leading to irreversible kidney failure. Considering the origin of the graft, several studies have reported differences between living (LD) and deceased donors (DD) in graft and patient survival. These differences seem to be related to multiple factors including, donor age and time of cold ischemia among others. Many of transplanted organs come from old-aged DDs, in which pre-transplant biopsy is recommended. However, kidney biopsy has several limitations, and there is a need to develop alternatives to assess the status of a kidney before transplantation. As the analysis of urinary extracellular vesicles (uEVs) rendered promising results as non-invasive biomarkers of kidney-related pathologies, this pilot study aimed to investigate whether profiling uEVs of LDs and DDs may be of help to assess the quality of the kidney before nephrectomy.MethodsuEVs from 5 living donors and 7 deceased donors were isolated by size-exclusion chromatography, and their protein and miRNA content were analysed by liquid chromatography followed by mass spectrometry and next generation sequencing, respectively. Then, hierarchical clustering and venn diagrams were done with Perseus software and InteractiVenn tool. Specific EVs data bases were also used for Gene Ontology analysis.ResultsNext generation sequencing revealed that uEVs from DDs contained less miRNAs than LDs, but most of the DD-expressed miRNAs were shared with LDs (96%). Only miR-326 (targeting the apoptotic-related Bcl2) was found significantly over-represented in LD. Focusing on the protein content, we detected a low intra-group correlation in both types of donors. Despite these differences, hierarchical clustering of either miRNA or protein data could not identify a differential profile between LDs and DDs. Of note, 90% of transplanted patients had a functional graft after a year from KTx.ConclusionsIn this pilot study we found that, in normo-functional grafts, minor differences in uEVs profile could not discriminate between LDs and DDs.
Highlights
Kidney transplantation (KTx) is the best therapeutic approach for chronic kidney diseases leading to irreversible kidney failure
Using size-exclusion chromatography (SEC) as a minimally altering isolation technique to obtain urinary extracellular vesicles (uEVs) [27], we report the great similarity in the molecular profile of uEVs from Living donor (LD) and deceased donors (DD)
Mean time of cold ischemia in the LD group was of 2.4 h
Summary
Kidney transplantation (KTx) is the best therapeutic approach for chronic kidney diseases leading to irreversible kidney failure. Some of the most important parameters affecting patient’s survival after transplantation are related to age (of both donor and recipient), previous pathology of the recipient and the extent of the ischemia-reperfusion injury [4, 6,7,8]. It is widely accepted, and strongly supported, that transplantation from LDs offers better long-term outcomes than deceased organ transplants [9,10,11]; because of DDs are usually older, have more comorbidities and longer cold ischemia time than LD [10,11,12]. All these maintaining interventions may modify the quality of the organ
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