The international surgical journal with global reach

This is the Scientific Surgery Archive, which contains all randomized clinical trials in surgery that have been identified by searching the top 50 English language medical journal issues since January 1998. Compiled by Jonothan J. Earnshaw, former Editor-in-Chief, BJS

Kidney graft outcome using an anti‐Xa therapeutic strategy in an experimental model of severe ischaemia–reperfusion injury. BJS 2015; 102: 132-142.

Published: 17th November 2014

Authors: S. Tillet, S. Giraud, P. O. Delpech, R. Thuillier, V. Ameteau, J. M. Goujon et al.

Background

Deceased after cardiac death donors represent an important source of organs to reduce organ shortage in transplantation. However, these organs are subjected to more ischaemia–reperfusion injury (IRI). Reducing IRI by targeting coagulation is studied here in an experimental model.

Method

The effect of an anti‐Xa compound (fondaparinux) was evaluated using an autotransplanted kidney model in pigs. Kidneys were clamped for 60 min (warm ischaemia) and then preserved for 24 h at 4°C in University of Wisconsin solution (UW). The anti‐Xa compound was injected intravenously before warm ischaemia and used during cold storage, and its effects were compared with those of intravenous injection of unfractionated heparin (UFH) before warm ischaemia and use during cold storage, or use of UW alone during cold storage.

Results

At 3 months after transplantation, anti‐Xa treatment improved recovery of renal function and chronic serum creatinine levels compared with UW and UFH (mean(s.e.m.) 89(4), 250(4) and 217(8) µmol/l respectively). The anti‐Xa treatment also reduced fibrosis, and decreased tissue expression of markers of the epithelial–mesenchymal transition compared with UW and UFH. Cleaved protease‐activated receptor 2 was overexpressed in the UW group compared with the anti‐Xa and UFH groups. Leucocyte infiltrates were decreased in the anti‐Xa group compared with the UW and UFH groups. Macrophage invasion was also decreased by anticoagulation treatment.

Conclusion

Peritransplant anticoagulation therapy was beneficial to graft outcome, in both the acute and chronic phases. Moreover, specific inhibition of coagulation Xa protease further protected kidney grafts, with better recovery and decreased expression of chronic lesion markers.

Surgical relevance

The increasing use of marginal donors highlights the importance of organ quality in transplantation. Renal ischaemia–reperfusion injury (IRI), which includes a deleterious activation of coagulation, plays a central role in determining graft quality and outcome.

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