Ex-Vivo Normothermic Perfusion (EVNP) Attenuation of Kidney Ischemia-Reperfusion Injury (IRI): A Proposed Mechanism.
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
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).
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 June 7, 2020.« Back to 2016 American Transplant Congress