A Novel Method to Improve Perfusion of Ex Vivo Pumped Human Kidneys.
Journal
Annals of surgery
ISSN: 1528-1140
Titre abrégé: Ann Surg
Pays: United States
ID NLM: 0372354
Informations de publication
Date de publication:
01 12 2021
01 12 2021
Historique:
pubmed:
6
12
2019
medline:
15
12
2021
entrez:
6
12
2019
Statut:
ppublish
Résumé
To determine if addition of the S-nitrosylating agent ethyl nitrite (ENO) to the preservation solution can improve perfusion parameters in pumped human kidneys. A significant percentage of actively stored kidneys experience elevations in resistance and decreases in flow rate during the ex vivo storage period. Preclinical work indicates that renal status after brain death is negatively impacted by inflammation and reduced perfusion-processes regulated by protein S-nitrosylation. To translate these findings, we added ENO to the preservation solution in an attempt to reverse the perfusion deficits observed in nontransplanted pumped human kidneys. After obtaining positive proof-of-concept results with swine kidneys, we studied donated human kidneys undergoing hypothermic pulsatile perfusion deemed unsuitable for transplantation. Control kidneys continued to be pumped a 4°C (ie, standard of care). In the experimental group, the preservation solution was aerated with 50 ppm ENO in nitrogen. Flow rate and perfusion were recorded for 10 hours followed by biochemical analysis of the kidney tissue. In controls, perfusion was constant during the monitoring period (ie, flow rate remained low and resistance stayed high). In contrast, the addition of ENO produced significant and sustained reductions in resistance and increases in flow rate. ENO-treated kidneys had higher levels of cyclic guanosine monophosphate, potentially explaining the perfusion benefits, and increased levels of interleukin-10, suggestive of an anti-inflammatory effect. S-Nitrosylation therapy restored the microcirculation and thus improved overall organ perfusion. Inclusion of ENO in the renal preservation solution holds promise to increase the number and quality of kidneys available for transplant.
Sections du résumé
OBJECTIVE
To determine if addition of the S-nitrosylating agent ethyl nitrite (ENO) to the preservation solution can improve perfusion parameters in pumped human kidneys.
BACKGROUND
A significant percentage of actively stored kidneys experience elevations in resistance and decreases in flow rate during the ex vivo storage period. Preclinical work indicates that renal status after brain death is negatively impacted by inflammation and reduced perfusion-processes regulated by protein S-nitrosylation. To translate these findings, we added ENO to the preservation solution in an attempt to reverse the perfusion deficits observed in nontransplanted pumped human kidneys.
METHODS
After obtaining positive proof-of-concept results with swine kidneys, we studied donated human kidneys undergoing hypothermic pulsatile perfusion deemed unsuitable for transplantation. Control kidneys continued to be pumped a 4°C (ie, standard of care). In the experimental group, the preservation solution was aerated with 50 ppm ENO in nitrogen. Flow rate and perfusion were recorded for 10 hours followed by biochemical analysis of the kidney tissue.
RESULTS
In controls, perfusion was constant during the monitoring period (ie, flow rate remained low and resistance stayed high). In contrast, the addition of ENO produced significant and sustained reductions in resistance and increases in flow rate. ENO-treated kidneys had higher levels of cyclic guanosine monophosphate, potentially explaining the perfusion benefits, and increased levels of interleukin-10, suggestive of an anti-inflammatory effect.
CONCLUSIONS
S-Nitrosylation therapy restored the microcirculation and thus improved overall organ perfusion. Inclusion of ENO in the renal preservation solution holds promise to increase the number and quality of kidneys available for transplant.
Identifiants
pubmed: 31804390
pii: 00000658-202112000-00052
doi: 10.1097/SLA.0000000000003702
doi:
Substances chimiques
IL10 protein, human
0
Nitrites
0
Organ Preservation Solutions
0
Interleukin-10
130068-27-8
Nitric Oxide
31C4KY9ESH
ethyl nitrite
8C7CJ279RV
Cyclic GMP
H2D2X058MU
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e610-e615Informations de copyright
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of interest: Drs Reynolds and Stamler hold patents related to renitrosylation some of which have been licensed for commercial development. Their institution is aware of these conflicts and appropriate management plans are in place. None of the other authors have relevant conflicts to disclose.
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