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

Valeria Mas, Kellie J. Archer, Catherine I. Dumur, Mariano J. Scian, Jihee L. Suh, Anne L. King, Megan E. Wardius, Julie A. Straub, Marc P. Posner, Kenneth Brayman, Daniel Maluf

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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<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. 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.

Original languageEnglish (US)
Article numbere35526
JournalPloS one
Volume7
Issue number4
DOIs
StatePublished - Apr 24 2012

Fingerprint

Cold storage
pumps
Genes
kidneys
Tissue Donors
Biopsy
Pumps
Kidney
Gene Expression
cold storage
Grafts
genes
Transplantation (surgical)
Cold Ischemia
biopsy
ischemia
Gene expression
probes (equipment)
Cell signaling
Delayed Graft Function

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation. / Mas, Valeria; Archer, Kellie J.; Dumur, Catherine I.; Scian, Mariano J.; Suh, Jihee L.; King, Anne L.; Wardius, Megan E.; Straub, Julie A.; Posner, Marc P.; Brayman, Kenneth; Maluf, Daniel.

In: PloS one, Vol. 7, No. 4, e35526, 24.04.2012.

Research output: Contribution to journalArticle

Mas, V, Archer, KJ, Dumur, CI, Scian, MJ, Suh, JL, King, AL, Wardius, ME, Straub, JA, Posner, MP, Brayman, K & Maluf, D 2012, 'Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation', PloS one, vol. 7, no. 4, e35526. https://doi.org/10.1371/journal.pone.0035526
Mas, Valeria ; Archer, Kellie J. ; Dumur, Catherine I. ; Scian, Mariano J. ; Suh, Jihee L. ; King, Anne L. ; Wardius, Megan E. ; Straub, Julie A. ; Posner, Marc P. ; Brayman, Kenneth ; Maluf, Daniel. / Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation. In: PloS one. 2012 ; Vol. 7, No. 4.
@article{5eeac2b7ec604292b40eb033b80c0c6d,
title = "Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation",
abstract = "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<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. 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.",
author = "Valeria Mas and Archer, {Kellie J.} and Dumur, {Catherine I.} and Scian, {Mariano J.} and Suh, {Jihee L.} and King, {Anne L.} and Wardius, {Megan E.} and Straub, {Julie A.} and Posner, {Marc P.} and Kenneth Brayman and Daniel Maluf",
year = "2012",
month = "4",
day = "24",
doi = "10.1371/journal.pone.0035526",
language = "English (US)",
volume = "7",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Reduced expression of inflammatory genes in deceased donor kidneys undergoing pulsatile pump preservation

AU - Mas, Valeria

AU - Archer, Kellie J.

AU - Dumur, Catherine I.

AU - Scian, Mariano J.

AU - Suh, Jihee L.

AU - King, Anne L.

AU - Wardius, Megan E.

AU - Straub, Julie A.

AU - Posner, Marc P.

AU - Brayman, Kenneth

AU - Maluf, Daniel

PY - 2012/4/24

Y1 - 2012/4/24

N2 - 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<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. 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.

AB - 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<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. 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.

UR - http://www.scopus.com/inward/record.url?scp=84860162540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860162540&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0035526

DO - 10.1371/journal.pone.0035526

M3 - Article

VL - 7

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e35526

ER -