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Mediators of Inflammation
Volume 2013, Article ID 501430, 10 pages
Clinical Study

Reactive Metabolites and AGE-RAGE-Mediated Inflammation in Patients following Liver Transplantation

1Department of Anesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
2Department of Medicine I and Clinical Chemistry, University of Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany
3Department of General and Transplant Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany
4Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany
5Department of Anesthesiology and Intensive Care Medicine, University of Gießen, Rudolf-Buchheim-Straße 7, 35392 Gießen, Germany

Received 11 December 2012; Accepted 29 April 2013

Academic Editor: Philipp Lepper

Copyright © 2013 Thorsten Brenner et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Recent investigations have indicated that reactive metabolites and AGE-RAGE-mediated inflammation might play an important role in the pathogenesis of ischemia-reperfusion injury in liver transplantation. In this observational clinical study, 150 patients were enrolled following liver transplantation from deceased donors. The occurrence of short-term complications within 10 days of transplantation was documented. Blood samples were collected prior to transplantation, immediately after transplantation, and at consecutive time points, for a total of seven days after transplantation. Plasma levels of methylglyoxal were determined using HPLC, whereas plasma levels of L-arginine, asymmetric dimethylarginine, advanced glycation endproducts-carboxylmethyllysine, soluble receptor for advanced glycation endproducts, and total antioxidant capacity were measured by ELISA. Patients following liver transplantation were shown to suffer from increased RAGE-associated inflammation with an AGE load mainly dependent upon reactive carbonyl species-derived AGEs. In contrast, carboxylmethyllysine-derived AGEs were of a minor importance. As assessed by the ratio of L-arginine/asymmetric dimethylarginine, the bioavailability of nitric oxide was shown to be reduced in hepatic IRI, especially in those patients suffering from perfusion disorders following liver transplantation. For the early identification of patients at high risk of perfusion disorders, the implementation of asymmetric dimethylarginine measurements in routine diagnostics following liver transplantation from deceased donors should be taken into consideration.