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Kidney Week

Abstract: FR-PO841

Normothermic Ex-Vivo Kidney Perfusion Restores the Gene Expression Profile of Marginal Kidney Grafts Subjected to Warm Ischemia

Session Information

  • Transplantation: Basic
    October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 1801 Transplantation: Basic

Authors

  • Urbanellis, Peter, University of Toronto, Toronto, Ontario, Canada
  • McEvoy, Caitriona M., University Health Network, Toronto, Toronto, Ontario, Canada
  • Linares, Ivan, University Health Network, Toronto, Ontario, Canada
  • Kollmann, Dagmar, Toronto General Hospital, Toronto, Ontario, Canada
  • Ganesh, Sujani, University Health Network, Toronto, Ontario, Canada
  • Mucsi, Istvan, University Health Network, Toronto, Ontario, Canada
  • Bagli, Darius, Hospital for sick children / univ of Toronto, Toronto, Ontario, Canada
  • Konvalinka, Ana, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Robinson, Lisa, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Selzner, Markus, Toronto General Hospital, Toronto, Ontario, Canada
Background

Normothermic ex-vivo kidney perfusion (NEVKP) results in improved marginal renal graft function compared to static cold storage (SCS) post-transplantation. To determine the mechanisms responsible for the beneficial effects of NEVKP, we investigated gene expression profiles of donation-after-cardiac-death (DCD) grafts stored with NEVKP or SCS to that of unmanipulated naïve-kidneys.

Methods

Kidneys from Yorkshire pigs were removed following 30-min of warm ischemia modelling DCD. Grafts were stored in SCS or NEVKP for 8hr prior to heterotopic autotransplantation. On POD3, grafts were collected and microarray analysis was performed.

Results

During NEVKP storage, DCD-grafts demonstrated favorable perfusion characteristics including lactate clearance, decreasing intra-renal resistance, and urine production. NEVKP resulted in improved graft function compared to SCS post-transplant with decreased peak serum creatinine (POD1: 4.0+/-1.15mg/dL vs POD3: 12.0+/0.78mg/dL, n=5, p<0.01) and higher creatinine clearance (POD3: 39.6+/-11.8mL/min vs 2.6+/-0.9mL/min, n=5, p<0.01). Transcriptomic analysis demonstrated significant differences in the expression of 27 genes in NEVKP grafts compared to naïve-kidneys (Table 1, >±2-fold change, n=3, FDR q<0.20). In contrast, 668 genes were differentially expressed between grafts stored with SCS and naïve-kidneys (Table 2, >±2-fold change, n=3, FDR q<0.20).

Conclusion

NEVKP of DCD kidney grafts resulted in a gene expression profile more closely resembling naïve kidneys. Conversely, grafts stored with SCS demonstrated increased expression of genes related to inflammation, apoptosis, and repair.