First-in-man controlled rewarming and normothermic perfusion with cell-free solution of a kidney prior to transplantation

Thomas Minor, Charlotte von Horn, Anja Gallinat, Moritz Kaths, Andreas Kribben, Jürgen Treckmann, Andreas Paul, Thomas Minor, Charlotte von Horn, Anja Gallinat, Moritz Kaths, Andreas Kribben, Jürgen Treckmann, Andreas Paul

Abstract

Cold preservation sensitizes organ grafts to exacerbation of tissue injury upon reperfusion. This reperfusion injury is not fully explained by the mere re-introduction of oxygen but rather is pertinent to the immediate rise in metabolic turnover associated with the abrupt restoration of normothermia. Here we report the first clinical case of gradual resumption of graft temperature upon ex vivo machine perfusion from hypothermia up to normothermic conditions using cell-free buffer as a perfusate. A kidney graft from an extended criteria donor was put on the machine after 12.5 hours of cold storage. During ex vivo perfusion, perfusion pressure and temperature were gradually elevated from 30 mm Hg and 8°C to 75 mm Hg and 35°C, respectively. Perfusate consisted of diluted Steen solution, oxygenated with 100% oxygen. Final flow rates at 35°C were 850 mL/min. The kidney was transplanted without complications and showed good immediate function. Serum creatinine fell from preoperative 720 µmol/L to 506 µmol/L during the first 24 hours after transplantation. Clearance after 1 week was 43.1 mL/min. Controlled oxygenated rewarming prior to transplantation can be performed up to normothermia without blood components or artificial oxygen carriers and may represent a promising tool to mitigate cold-induced reperfusion injury or to evaluate graft performance.

Keywords: clinical research/practice; kidney transplantation/nephrology; organ perfusion and preservation; organ transplantation in general; tissue injury and repair.

© 2019 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.

References

REFERENCES

    1. Metzger RA, Delmonico FL, Feng S, Port FK, Wynn JJ, Merion RM. Expanded criteria donors for kidney transplantation. Am J Transplant. 2003;3(Suppl 4):114-125.
    1. Nicholson ML, Hosgood SA. Renal transplantation after ex vivo normothermic perfusion: the first clinical study. Am J Transplant. 2013;13(5):1246-1252.
    1. Kaths JM, Cen JY, Chun YM, et al. Continuous normothermic ex vivo kidney perfusion is superior to brief normothermic perfusion following static cold storage in donation after circulatory death pig kidney transplantation. Am J Transplant. 2017;17(4):957-969.
    1. Minor T, von Horn C. Rewarming injury after cold preservation. Int J Mol Sci. 2019;20(9):2059.
    1. von Horn C, Minor T. Improved approach for normothermic machine perfusion of cold stored kidney grafts. Am J Transl Res. 2018;10:1921-1929.
    1. Kameneva MV, Undar A, Antaki JF, Watach MJ, Calhoon JH, Borovetz HS. Decrease in red blood cell deformability caused by hypothermia, hemodilution, and mechanical stress: factors related to cardiopulmonary bypass. ASAIO J. 1999;45(4):307-310.
    1. Minor T, von Horn C, Paul A. Role of erythrocytes in short-term rewarming kidney perfusion after cold storage. Artif Organs. 2019;43(6):584-592.
    1. Rao PS, Schaubel DE, Guidinger MK, et al. A comprehensive risk quantification score for deceased donor kidneys: the kidney donor risk index. Transplantation. 2009;88(2):231-236.
    1. Kurnik BR, Weisberg LS, Kurnik PB. Renal and systemic oxygen consumption in patients with normal and abnormal renal function. J Am Soc Nephrol. 1992;2(11):1617-1626.
    1. Mazilescu LI, Selzner M. Kidney machine preservation: state of the art. Curr Transplant Rep. 2019;6:234-241.
    1. Gracia-Sancho J, Villarreal G Jr, Zhang Y, et al. Flow cessation triggers endothelial dysfunction during organ cold storage conditions: strategies for pharmacologic intervention. Transplantation. 2010;90(2):142-149.
    1. Gallinat A, Fox M, Luer B, Efferz P, Paul A, Minor T. Role of pulsatility in hypothermic reconditioning of porcine kidney grafts by machine perfusion after cold storage. Transplantation. 2013;96:538-542.
    1. Schlegel A, Kron P, Dutkowski P. Hypothermic oxygenated liver perfusion: basic mechanisms and clinical application. Curr Transplant Rep. 2015;2(1):52-62.
    1. Minor T, von Horn C, Paul A. Role of temperature in reconditioning and evaluation of cold preserved kidney and liver grafts. Curr Opin Organ Transplant. 2017;22(3):267-273.
    1. Leducq N, Delmas-Beauvieux MC, Bourdel-Marchasson I, et al. Mitochondrial permeability transition during hypothermic to normothermic reperfusion in rat liver demonstrated by the protective effect of cyclosporin A. Biochem J. 1998;336(Pt 2):501-506.
    1. Minor T, Efferz P, Fox M, Wohlschlaeger J, Luer B. Controlled oxygenated rewarming of cold stored liver grafts by thermally graduated machine perfusion prior to reperfusion. Am J Transplant. 2013;13(6):1450-1460.
    1. Mahboub P, Ottens P, Seelen M, et al. Gradual rewarming with gradual increase in pressure during machine perfusion after cold static preservation reduces kidney ischemia reperfusion injury. PLoS ONE. 2015;10(12);e0143859.
    1. Schopp I, Reissberg E, Luer B, Efferz P, Minor T. Controlled rewarming after hypothermia: adding a new principle to renal preservation. Clin Transl Sci. 2015;8(5):475-478.
    1. von Horn C, Baba HA, Hannaert P, et al. Controlled oxygenated rewarming up to normothermia for pretransplant reconditioning of liver grafts. Clin Transplant. 2017;31(11):e13101.
    1. Mamikonian LS, Mamo LB, Smith PB, Koo J, Lodge AJ, Turi JL. Cardiopulmonary bypass is associated with hemolysis and acute kidney injury in neonates, infants, and children*. Pediatr Crit Care Med. 2014;15(3):e111-e119.

Source: PubMed

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