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Perfusion of Porcine Kidneys With Macromolecular Heparin Reduces Early Ischemia Reperfusion Injury

Sedigh, Amir, MD, PhD1; Nordling, Sofia, PhD2; Carlsson, Fredrik, PhD2; Larsson, Erik, MD, PhD3; Norlin, Bo4; Lübenow, Norbert, MD, PhD2; Lennmyr, Fredrik, MD, PhD4; Tufveson, Gunnar, MD, PhD1; Magnusson, Peetra U., PhD2; Lorant, Tomas, MD, PhD1

doi: 10.1097/TP.0000000000002469
Original Clinical Science—General

Background Previously, we have been able to demonstrate the possibility of coating the inner surface of the renal arteries in porcine kidneys with a heparin conjugate during hypothermic machine perfusion (HMP). The purpose of this study was to assess the efficacy of this treatment in reducing early ischemia-reperfusion injury.

Method Brain death was induced in male landrace pigs by stepwise volume expansion of an epidural balloon catheter until negative cerebral perfusion pressure (CPP) was obtained. Both kidneys (matched pairs; n = 6 + 6) were preserved for 20 hours by HMP during which 50 mg heparin conjugate was added to one of the HMP systems (treated group). A customized ex vivo normothermic oxygenated perfusion (NP) system with added exogenous creatinine was used to evaluate early kidney function. Blood, urine and histological samples were collected during the subsequent 3 hours of NP.

Results Kidney weight was lower at the end of NP (P = 0.017) in the treated group compared with control kidneys. The rate of decline in creatinine level was faster (P = 0.024), total urinary volume was higher (P = 0.031), and the level of urine neutrophil gelatinase-associated lipocalin (NGAL) was lower (P = 0.031) in the treated group. Histologically, less tubular changes were seen (P = 0.046). During NP intrarenal resistance remained lower (P < 0.0001) in the treated group.

Conclusions Perfusion of porcine kidneys with heparin conjugate during HMP reduces preservation injury and improves organ function shortly after reperfusion. No increased risk of bleeding was seen in this setup. This protective strategy may potentially improve the quality of transplanted kidneys in the clinical setting.

The authors demonstrate that perfusion of porcine kidneys with heparin conjugate during hypothermic machine perfusion reduces preservation injury and improves organ function shortly after reperfusion.

1 Section of Transplantation Surgery, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

2 Section of Clinical Immunology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

3 Section of Molecular and Morphological Pathology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.

4 Section of Anaesthesiology and Intensive Care, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Received 9 April 2018. Revision received 3 September 2018.

Accepted 12 September 2018.

This work was supported by grants from the Kidney Foundation, the Lars-Erik Gelin Memorial Foundation, the Eriksson Foundation, the Uppsala BIO's BIO-X program, the Swedish Governmental Agency for Innovation Systems (Vinnova) and the Uppsala University Hospital.

F.C. is employed as a researcher at Corline Biomedical AB. G.T. works as Chief Medical Officer for Corline Biomedical AB. The other authors declare no conflicts of interest.

A.S. participated in the research design, writing of the article, performance of the research, and data analysis. S.N. participated in the research design, writing of the article, performance of the research. F.C. participated in the research and data analysis. E.L. participated in the research and data analysis. B.N. participated in the research and performance of the research. N.L. participated in the research and data analysis. F.L. participated in the research and data analysis. G.T. participated in the research and data analysis. P.M. participated in the research design, writing of the article and data analysis. T.L. participated in the research design, writing of the article, performance of the research, and critical analysis and review of the data. All authors have approved the final version of the article.

Correspondence: Amir Sedigh, MD, Department of Surgical Sciences Section of Transplantation Surgery Uppsala University Hospital, SE-751 85 Uppsala, Sweden. (amir.sedigh@surgsci.uu.se).

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