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Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation.

ABSTRACT: 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.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<0.001). Donor age (42.0±14.6 vs. 34.1±14.2 years, P?=?0.009) and the percentage of ECD kidneys (PPP?=?35% vs. CSP?=?12.8%, P?=?0.012) were significantly different between groups. A two-sample t-test was performed, and probe sets having a P<0.001 were considered significant. Probe set level linear models were fit using cold ischemia time and CSP/PPP as independent variables to determine significant probe sets (P<0.001) between groups after adjusting for cold ischemia time. Thus, 43 significant genes were identified (P<0.001). Over-expression of genes associated with inflammation (CD86, CD209, CLEC4, EGFR2, TFF3, among others) was observed in the CSP group. Cell-to-cell signaling and interaction, and antigen presentation were the most important pathways with genes significantly over-expressed in CSP kidneys. When the analysis was restricted to ECD kidneys, genes involved in inflammation were also differentially up-regulated in ECD kidneys undergoing CSP. However, graft survival at the end of the study was similar between groups (P?=?0.2). Moreover, the incidence of delayed graft function was not significant between groups.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.

SUBMITTER: Mas VR

PROVIDER: S-EPMC3335841 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation.

Mas Valeria R VR Archer Kellie J KJ Dumur Catherine I CI Scian Mariano J MJ Suh Jihee L JL King Anne L AL Wardius Megan E ME Straub Julie A JA Posner Marc P MP Brayman Kenneth K Maluf Daniel G DG

PloS one 20120424 4

<h4>Background</h4>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.<h4>Methodology/principal findings</h4>99 pre-implantation DDK biopsies were studied using gene expression with GeneChips. Kidneys transplant recipients were ...[more]

PMID: 22545113

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Project description:Background and objectivesBiopsies taken at deceased donor kidney procurement continue to be cited as a leading reason for discard; however, the reproducibility and prognostic capability of these biopsies are controversial.Design, setting, participants, & measurementsWe compiled a retrospective, single-institution, continuous cohort of deceased donor kidney transplants performed from 2006 to 2009. Procurement biopsy information-percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease-was obtained from the national transplant database. Using univariable, multivariable, and time-to-event analyses for death-censored graft survival, we compared procurement frozen section biopsy reports with reperfusion paraffin-embedded biopsies read by trained kidney pathologists (n=270). We also examined agreement for sequential procurement biopsies performed on the same kidney (n=116 kidneys).ResultsFor kidneys on which more than one procurement biopsy was performed (n=116), category agreement was found in only 64% of cases (κ=0.14). For all kidneys (n=270), correlation between procurement and reperfusion biopsies was poor: overall, biopsies were classified into the same category (optimal versus suboptimal) in only 64% of cases (κ=0.25). This discrepancy was most pronounced when categorizing percentage of glomerulosclerosis, which had 63% agreement (κ=0.15). Interstitial fibrosis/tubular atrophy and vascular disease had agreement rates of 82% (κ=0.13) and 80% (κ=0.15), respectively. Ninety-eight (36%) recipients died, and 56 (21%) allografts failed by the end of follow-up. Reperfusion biopsies were more prognostic than procurement biopsies (hazard ratio for graft failure, 2.02; 95% confidence interval, 1.09 to 3.74 versus hazard ratio for graft failure, 1.30; 95% confidence interval, 0.61 to 2.76), with procurement biopsies not significantly associated with graft failure.ConclusionsWe found that procurement biopsies are poorly reproducible, do not correlate well with paraffin-embedded reperfusion biopsies, and are not significantly associated with transplant outcomes.

Dataset Information

Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation.

Publications

Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation.

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