Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs

J. Yoshida, K. S. Ozaki, M. A. Nalesnik, S. Ueki, M. Castillo-Rama, G. Faleo, M. Ezzelarab, Atsunori Nakao, B. Ekser, G. J. Echeverri, M. A. Ross, D. B. Stolz, N. Murase

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

I/R injury is a major deleterious factor of successful kidney transplantation (KTx). Carbon monoxide (CO) is an endogenous gaseous regulatory molecule, and exogenously delivered CO in low concentrations provides potent cytoprotection. This study evaluated efficacies of CO exposure to excised kidney grafts to inhibit I/R injury in the pig KTx model. Porcine kidneys were stored for 48 h in control UW or UW supplemented with CO (CO-UW) and autotransplanted in a 14-day follow-up study. In the control UW group, animal survival was 80% (4/5) with peak serum creatinine levels of 12.0 ± 5.1 mg/dL. CO-UW showed potent protection, and peak creatinine levels were reduced to 6.9 ± 1.4 mg/dL with 100% (5/5) survival without any noticeable adverse event or abnormal COHb value. Control grafts at 14 days showed significant tubular damages, focal fibrotic changes and numerous infiltrates. The CO-UW group showed significantly less severe histopathological changes with less TGF-β and p-Smad3 expression. Grafts in CO-UW also showed significantly lower early mRNA levels for proinflammatory cytokines and less lipid peroxidation. CO in UW provides significant protection against renal I/R injury in the porcine KTx model. Ex vivo exposure of kidney grafts to CO during cold storage may therefore be a safe strategy to reduce I/R injury

Original languageEnglish
Pages (from-to)763-772
Number of pages10
JournalAmerican Journal of Transplantation
Volume10
Issue number4
DOIs
Publication statusPublished - Apr 2010
Externally publishedYes

Fingerprint

Carbon Monoxide
Reperfusion Injury
Swine
Transplants
Kidney
Wounds and Injuries
Creatinine
University of Wisconsin-lactobionate solution
Cytoprotection
Kidney Transplantation
Lipid Peroxidation
Cytokines
Control Groups
Messenger RNA

Keywords

  • Carbon monoxide
  • Interstitial fibrosis
  • Ischemia/reperfusion injury
  • Kidney transplantation
  • Large animal model

ASJC Scopus subject areas

  • Transplantation
  • Immunology and Allergy
  • Pharmacology (medical)

Cite this

Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs. / Yoshida, J.; Ozaki, K. S.; Nalesnik, M. A.; Ueki, S.; Castillo-Rama, M.; Faleo, G.; Ezzelarab, M.; Nakao, Atsunori; Ekser, B.; Echeverri, G. J.; Ross, M. A.; Stolz, D. B.; Murase, N.

In: American Journal of Transplantation, Vol. 10, No. 4, 04.2010, p. 763-772.

Research output: Contribution to journalArticle

Yoshida, J, Ozaki, KS, Nalesnik, MA, Ueki, S, Castillo-Rama, M, Faleo, G, Ezzelarab, M, Nakao, A, Ekser, B, Echeverri, GJ, Ross, MA, Stolz, DB & Murase, N 2010, 'Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs', American Journal of Transplantation, vol. 10, no. 4, pp. 763-772. https://doi.org/10.1111/j.1600-6143.2010.03040.x
Yoshida, J. ; Ozaki, K. S. ; Nalesnik, M. A. ; Ueki, S. ; Castillo-Rama, M. ; Faleo, G. ; Ezzelarab, M. ; Nakao, Atsunori ; Ekser, B. ; Echeverri, G. J. ; Ross, M. A. ; Stolz, D. B. ; Murase, N. / Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs. In: American Journal of Transplantation. 2010 ; Vol. 10, No. 4. pp. 763-772.
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