Reduced Expression of Inflammatory Genes in Deceased Donor Kidneys Undergoing Pulsatile Pump Preservation

Background The use of expanded criteria donor kidneys (ECD) had been associated with worse outcomes. Whole gene expression of pre-implantation allograft biopsies from deceased donor kidneys (DDKs) was evaluated to compare the effect of pulsatile pump preservation (PPP) vs. cold storage preservation (CSP) on standard and ECD kidneys. Methodology/Principal Findings 99 pre-implantation DDK biopsies were studied using gene expression with GeneChips. Kidneys transplant recipients were followed post transplantation for 35.8 months (range = 24–62). The PPP group included 60 biopsies (cold ischemia time (CIT) = 1,367+/−509 minutes) and the CSP group included 39 biopsies (CIT = 1,022+/−485 minutes) (P Conclusions/Significance Inflammation was the most important up-regulated pattern associated with pre-implantation biopsies undergoing CSP even when the PPP group has a larger number of ECD kidneys. No significant difference was observed in delayed graft function incidence and graft function post-transplantation. These findings support the use of PPP in ECD donor kidneys

Top scoring network of differentially expressed genes between CSP and PPP kidneys.

<p>The top-scoring network of interactions among the probe sets identified as significantly differentially expressed when comparing CSP <i>vs.</i> PPP kidneys. The probe sets were subsequently analyzed using the Ingenuity Pathway Analysis software (<a href="https://analysis.ingenuity.com" target="_blank">https://analysis.ingenuity.com</a>). This software is designed to identify dynamically generated biological networks, global canonical pathways and global functions. Interconnection of significant functional networks, where molecule nodes in different shades of red and green or white depending on being up-regulated and down-regulated or no-change, respectively, in CSP samples.</p

Inflammatory response in ECD-CSP kidneys.

<p>One-hundred and two differentially expressed probe sets were identified from the analysis of ECD kidneys preserved using PPP <i>vs.</i> CSP. From the gene list, the scoring network functions included inflammatory response and cell death (score 25) when using Pathway Analysis software.</p

Characteristics of ECD^* donor kidneys preserved using PPP and CSP.

*<p>ECD defined as previously described <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035526#pone.0035526-UNOS1" target="_blank">[7]</a>.</p><p>AA: African-Americans, M: Male, DGF: Delayed Graft Function.</p

Differentially expressed genes between CSP and PPP kidneys with prolonged CIT.

<p>Eighteen probe sets were differentially expressed when CIT was higher than 1,200 minutes and not significant between groups (CSP <i>vs.</i> PPP). Pathway Analysis showed that almost all these genes belong to the same network (score 23) and associate with the inflammatory response and immune cell trafficking.</p