Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Normothermic ex-vivo kidney perfusion (NEVKP) was shown to prevent delayed graft function of kidneys subjected to prolonged warm ischemia (WI) compared to static cold storage (SCS). To identify mechanisms for this finding, we analyzed the genomic profile of these grafts following storage to that of unmanipulated-naïve kidneys.
*Methods: Kidneys from 30kg-Yorkshire pigs were removed following 120min of WI and subjected to 8hrs of SCS or NEVKP. Kidney biopsies were collected on POD3 and gene expression was compared with naïve porcine kidneys utilizing the Affymetrix GeneChip® Porcine Gene 1.0 ST Array.
*Results: During NEVKP perfusion, 120min WI-grafts demonstrated favourable perfusion characteristics including lactate clearance (0hr:10.48±0.93mmol/L vs 7hr:1.48±0.85mmol/L,p<0.01,n=5), decreasing intra-renal resistance (0hr:2.26±0.9mmHg/mL/min vs 7hr:0.37±0.6mmHg/mL/min,p<0.01,n=5), and urine production. Post-transplantation, 120min WI-grafts with NEVKP, compared to SCS, demonstrated significantly decreased serum creatinine peak values (POD4:12.62±2.34mg/dl vs POD5:18.95±1.11mg/dL,p=0.001) and higher creatinine clearance (POD4:6.61±4.03mL/min vs 0.35±0.30mL/min,p=0.02). Comparison of POD3 transcript expression levels of 120min WI-grafts subjected to NEVKP or SCS to naïve kidneys showed significant alterations in 5703 and 4699 genes, respectively (>±2-fold changes in expression over naïve,n=3,p<0.05, FDR<0.05). Genes related to regeneration and inflammation were among the most highly over expressed in SCS grafts with metabolism-associated genes highly downregulated (table 1). In contrast, genes related to regeneration were less elevated following NEVKP (table 2).
*Conclusions: Grafts damaged by prolonged WI highly over-express genes associated with regeneration. Lower levels of these genes in NEVKP with preserved metabolism-related genes likely correlates to earlier graft repair and/or less damage during storage.
To cite this abstract in AMA style:Urbanellis P, Mazilescu L, McEvoy C, Ganesh S, John R, Mucsi I, Ghanekar A, Bagli D, Konvalinka A, Robinson L, Selzner M. Genome-Wide Transcriptome Analysis of Extreme Marginal Renal Grafts Indicates Earlier Repair and Less Damage Following Normothermic Ex-Vivo Kidney Perfusion Preservation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/genome-wide-transcriptome-analysis-of-extreme-marginal-renal-grafts-indicates-earlier-repair-and-less-damage-following-normothermic-ex-vivo-kidney-perfusion-preservation/. Accessed March 6, 2021.
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