Клинический протокол гипотермической оксигенированной перфузии (HOPE) и контролируемой оксигенированной реваскуляризации (COR) печени и почек

Клинический протокол описывает применение гипотермической оксигенированной перфузии (HOPE) и контролируемой оксигенированной реваскуляризации (COR) для улучшения качества донорских органов печени и почек. Протокол основан на международных и отечественных исследованиях, демонстрирующих снижение частоты билиарных осложнений и ранней дисфункции трансплантата при использовании машинной перфузии. HOPE рекомендуется для органов от доноров с асистолией и расширенными критериями, в то время как COR применяется для оценки маргинальных органов. Протокол включает детальное описание показаний, противопоказаний, технических аспектов перфузии, мониторинга и оценки жизнеспособности органов с использованием биомаркеров, таких как флавин мононуклеотид, сукцинат, маркеры апоптоза, некроптоза и ферроптоза. Представлены собственные результаты авторов, подтверждающие эффективность методов в снижении осложнений и улучшении исходов трансплантации.

1. Schlegel A, Muller X, Kalisvaart M, et al. Outcomes of DCD liver transplantation using organs treated by hypothermic oxygenated perfusion before implantation. Journal of Hepatology. 2019;70:50-57.

2. van Rijn R, Karimian N, Matton APM, et al. Dual hypothermic oxygenated machine perfusion in liver transplants donated after circulatory death. British Journal of Surgery. 2017;104:907-917.

3. Patrono D, Surra A, Catalano G, et al. Hypothermic oxygenated machine perfusion of liver grafts from brain-dead donors. Scientific Reports. 2019;9:9337.

4. Czigany Z, Lurje I, Tolba RH, et al. Machine perfusion for liver transplantation in the era of marginal organs – New kids on the block. Liver International. 2019;39:228-249.

5. Nasralla D, Coussios CC, Mergental H, et al. A randomized trial of normothermic preservation in liver transplantation. Nature. 2018;557:50-56.

6. Schlegel A, Mergental H, Fondevila C, et al. Machine perfusion of the liver and bioengineering. Journal of Hepatology. 2023;78:1181-1198.

7. Moers C, Smits JM, Maathuis MH, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. New England Journal of Medicine. 2009;360:7-19.

8. Jochmans I, Brat A, Davies L, et al. Oxygenated versus standard cold perfusion preservation in kidney transplantation (COMPARE): a randomised, double-blind, paired, phase 3 trial. Lancet. 2020;396:1653-1662.

9. Hosgood SA, Nicholson ML. First in man renal transplantation after ex vivo normothermic perfusion. Transplantation. 2011;92:735-738.

10. Kaths JM, Echeverri J, Linares I, et al. Normothermic ex vivo kidney perfusion for graft quality assessment prior to transplantation. American Journal of Transplantation. 2018;18:580-589.

11. van Leeuwen OB, de Vries Y, Fujiyoshi M, et al. Transplantation of high-risk donor livers after ex situ resuscitation and assessment using combined hypo- and normothermic machine perfusion: a prospective clinical trial. Annals of Surgery. 2019;270:906-914.

12. Mergental H, Laing RW, Kirkham AJ, et al. Transplantation of discarded livers following viability testing with normothermic machine perfusion. Nature Communications. 2020;11:2939.

13. Hoyer DP, Mathe Z, Gallinat A, et al. Controlled oxygenated rewarming of cold stored livers prior to transplantation: First clinical application of a new concept. Transplantation. 2016;100:147-152.

14. Schlegel A, Kron P, Graf R, et al. Warm vs. cold perfusion techniques to rescue rodent liver grafts. Journal of Hepatology. 2014;61:1267-1275.

15. Dutkowski P, Polak WG, Muiesan P, et al. First comparison of hypothermic oxygenated perfusion versus static cold storage of human donation after cardiac death liver transplants: an international-matched case analysis. Annals of Surgery. 2015;262:764-770.

16. Bruinsma BG, Yeh H, Özer S, et al. Subnormothermic machine perfusion for ex vivo preservation and recovery of the human liver for transplantation. American Journal of Transplantation. 2014;14:1400-1409.

17. Ravaioli M, De Pace V, Angeletti A, et al. Hypothermic oxygenated new machine perfusion system in liver and kidney transplantation of extended criteria donors: first Italian clinical trial. Scientific Reports. 2020;10:6063.

18. Detelich D, Markmann JF. The dawn of liver perfusion machines. Current Opinion in Organ Transplantation. 2018;23:151-161.

19. Karangwa SA, Dutkowski P, Fontes P, et al. Machine perfusion of donor livers for transplantation: a proposal for standardized nomenclature and reporting guidelines. American Journal of Transplantation. 2016;16:2932-2942.

20. van Leeuwen OB, de Vries Y, Fujiyoshi M, et al. Flavin mononucleotide during ex vivo machine perfusion is a reliable predictor of human donor liver viability and post-transplant graft recovery. Liver Transplantation. 2022;28:1699-1709.

21. de Vries Y, Matton APM, Nijsten MWN, et al. Pretransplant sequential hypo- and normothermic machine perfusion of suboptimal livers donated after circulatory death using a hemoglobin-based oxygen carrier perfusion solution. American Journal of Transplantation. 2019;19:1202-1211.

22. Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. Cell. 2017;171:273-285.

23. Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060-1072.

24. Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell. 2014;156:317-331.

25. Doll S, Freitas FP, Shah R, et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature. 2019;575:693-698.

26. Bersuker K, Hendricks JM, Li Z, et al. The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis. Nature. 2019;575:688-692.

27. Friedmann Angeli JP, Schneider M, Proneth B, et al. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nature Cell Biology. 2014;16:1180-1191.

28. Linkermann A, Skouta R, Himmerkus N, et al. Synchronized renal tubular cell death involves ferroptosis. Proceedings of the National Academy of Sciences. 2014;111:16836-16841.

29. Li Y, Feng D, Wang Z, et al. Ischemia-induced ACSL4 activation contributes to ferroptosis-mediated tissue injury in intestinal ischemia/reperfusion. Cell Death and Differentiation. 2019;26:2284-2299.

30. Yamada N, Karasawa T, Wakiya T, et al. Ferroptosis driven by radical oxidation of n-6 polyunsaturated fatty acids mediates hepatotoxicity and tumorigenesis. Cell Metabolism. 2020;32:144-159.

31. Kagan VE, Mao G, Qu F, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nature Chemical Biology. 2017;13:81-90.

32. Wenzel SE, Tyurina YY, Zhao J, et al. PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals. Cell. 2017;171:628-641.

33. Doll S, Proneth B, Tyurina YY, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nature Chemical Biology. 2017;13:91-98.

34. Mayr L, Grabherr F, Schwärzler J, et al. Dietary lipids fuel GPX4-restricted enteritis resembling Crohn's disease. Nature Communications. 2020;11:1775.

35. Degterev A, Huang Z, Boyce M, et al. Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nature Chemical Biology. 2005;1:112-119.

36. Linkermann A, Bräsen JH, Darding M, et al. Two independent pathways of regulated necrosis mediate ischemia-reperfusion injury. Proceedings of the National Academy of Sciences. 2013;110:12024-12029.

37. Muller T, Dewitz C, Schmitz J, et al. Necroptosis and ferroptosis are alternative cell death pathways that operate in acute kidney failure. Cellular and Molecular Life Sciences. 2017;74:3631-3645.

38. Zhang Y, Su SS, Zhao S, et al. RIP1 autophosphorylation is promoted by mitochondrial ROS and is essential for RIP3 recruitment into necrosome. Nature Communications. 2017;8:14329.

39. Sun L, Wang H, Wang Z, et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012;148:213-227.

40. Choi ME, Price DR, Ryter SW, Choi AMK. Necroptosis: a crucial pathogenic mediator of human disease. JCI Insight. 2019;4:e128834.