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Ex-Vivo Normothermic Perfusion (EVNP) Attenuation of Kidney Ischemia-Reperfusion Injury (IRI): A Proposed Mechanism.

I. Palma,1 S. Kabagambe,1 Y. Smolin,1 T. Boyer,1 I. Palma,1 O. Fiehn,2 Y.-J. Chen,1 J. Sageshima,1 C. Santhanakrishnan,1 C. Troppmann,1 R. Perez.1

1Department of Surgery, University of California, Davis Medical Center, Sacramento, CA
2Department of Molecular and Cellular Biology &
Genome Center, University of California-Davis, Davis, CA.

Meeting: 2016 American Transplant Congress

Abstract number: C99

Keywords: Ischemia, Kidney, Lipids, Machine preservation

Session Information

Date: Monday, June 13, 2016

Session Name: Poster Session C: Ischemia Reperfusion Injury and Organ Preservation

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Halls C&D

Related Abstracts
  • Creation of a Small Animal Model of Ex-Vivo Normothermic Perfusion (EVNP) for Treatment of Kidney Ischemia-Reperfusion (I/R) Injury.
  • Successful Ex-Vivo Normothermic Machine Perfusion and Viability Testing of Discarded Human Donor Livers

Introduction: EVNP has the potential to repair deceased donor renal IRI. We hypothesize that EVNP may attenuate renal IRI via alteration of lipid metabolism.

Methods: Eight paired human kidneys unsuitable for transplantation were placed on EVNP, at 37 ̊ C, for 3 hours. Kidneys were perfused with leukocyte depleted packed red blood cells (PRBC) as an optimal “repair” solution or whole blood (WB) to simulate early allograft IRI. Blood and urine samples were collected for pH, oxygen, electrolytes, creatinine, and lactate. Renal biopsies were collected and lipid metabolomic profiles generated using gas chromatography-mass spectrometry. Results were analyzed by paired t-test.

Results: Kidneys perfused with PRBC showed favorable hemodynamic and functional parameters. Fatty acid metabolites such as arachidonic and linoleic acid showed a greater magnitude of decrease after PRBC perfusion. Arachidonic acid post perfusion levels in PRBC compared to WB perfusion were lower. (10777 + 1740 to 16027 + 4233, respectively, p=0.0271). In addition, renal linoleic acid levels showed the same trend as arachidonic acid (1155 + 250.3 to 1861 + 321.4, respectively, p=0.0858). Four lysophospholipids (LPC) were found to have a greater magnitude of decrease in PRBC than WB

 

WB 

Pre-Perfusion

WB

Post-Perfusion

PRBC 

Pre-Perfusion

PRBC

Post-Perfusion

 

p-value

LPC (16:0) 224173 125167* 260414 105413* 0.5326+
LPC (18:0) 101847 75094 108419 55506* 0.1201+
LPC (18:1) 53351 21215 62907 15372* 0.3068+
LPC (18:2) 100265 8226 88629 9081* 0.6001
LPC (20:4) 42294 6635* 47693 7127 0.5128

* indicates statistical significance (p<0.05) between pre and post perfusion in each perfusion group. p-values not show

+lower level of metabolite in PRBC post perfusion compared to WB post perfusion

.

Conclusion: EVNP of deceased donor kidneys is associated with decreased production of fatty acids and lysophospholids, both inflammatory metabolites of Phospholipase A2. Further studies are necessary to determine whether EVNP induced alteration of lipid metabolism is an important protective mechanism in renal IRI.

CITATION INFORMATION: Palma I, Kabagambe S, Smolin Y, Boyer T, Palma I, Fiehn O, Chen Y.-J, Sageshima J, Santhanakrishnan C, Troppmann C, Perez R. Ex-Vivo Normothermic Perfusion (EVNP) Attenuation of Kidney Ischemia-Reperfusion Injury (IRI): A Proposed Mechanism. Am J Transplant. 2016;16 (suppl 3).

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To cite this abstract in AMA style:

Palma I, Kabagambe S, Smolin Y, Boyer T, Palma I, Fiehn O, Chen Y-J, Sageshima J, Santhanakrishnan C, Troppmann C, Perez R. Ex-Vivo Normothermic Perfusion (EVNP) Attenuation of Kidney Ischemia-Reperfusion Injury (IRI): A Proposed Mechanism. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/ex-vivo-normothermic-perfusion-evnp-attenuation-of-kidney-ischemia-reperfusion-injury-iri-a-proposed-mechanism/. Accessed February 28, 2021.

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