Mechanism of ischemia-reperfusion injury in renal transplantation and its impact on transplanted kidneys

doi:10.3877/cma.j.issn.1674-3903.2025.01.008

Abstract

Abstract:

The process of kidney transplantation surgery inevitably involves a phase of kidney ischemia and reperfusion, resulting in damage to the kidney's ischemia-reperfusion injury (IRI),which is intimately linked to the initial functional recuperation and prolonged survival of the transplanted organ. Presently, definitive and efficacious methods for clinical prevention and treatment remain elusive. A thorough examination of how IRI functions in transplanted kidneys offers both theoretical and scientific foundations for creating novel protective approaches. This review discusses the mechanisms of IRI and its impact on renal allograft.

Key words: Ischemia-reperfusion injury, Kidney transplantation, Oxidative stress, Cell death, Inflammation reaction

Yixuan Li, Meihe Li, Jin Zheng. Mechanism of ischemia-reperfusion injury in renal transplantation and its impact on transplanted kidneys[J]. Chinese Journal of Transplantation(Electronic Edition), 2025, 19(01): 43-49.

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References 54

1	Zhao H, Alam A, Soo AP, et al. Ischemia-reperfusion injury reduces long term renal graft survival： mechanism and beyond[J].EBioMedicine, 2018, 28： 31-42.
2	Ornellas FM, Ornellas DS, Martini SV, et al. Bone marrow-derived mononuclear cell therapy accelerates renal ischemia-reperfusion injury recovery by modulating inflammatory, antioxidant and apoptotic related molecules[J]. Cell Physiol Biochem, 2017, 41(5)： 1736-1752.
3	Tejchman K, Kotfis K, Sieńko J. Biomarkers and mechanisms of oxidative stress-last 20 years of research with an emphasis on kidney damage and renal transplantation[J]. Int J Mol Sci, 2021, 22(15)：8010.
4	Su L, Zhang J, Gomez H, et al. Mitochondria ROS and mitophagy in acute kidney injury[J]. Autophagy, 2023, 19(2)： 401-414.
5	Raedschelders K, Ansley DM, Chen DD. The cellular and molecular origin of reactive oxygen species generation during myocardial ischemia and reperfusion[J]. Pharmacol Ther, 2012, 133(2)： 230-255.
6	Li J, Cao F, Yin HL, et al. Ferroptosis： past, present and future[J]. Cell Death Dis, 2020, 11(2)： 88.
7	Wu J, Wang Y, Jiang R, et al. Ferroptosis in liver disease： new insights into disease mechanisms[J]. Cell Death Discov, 2021, 7(1)： 276.
8	Dar WA, Sullivan E, Bynon JS, et al. Ischaemia reperfusion injury in liver transplantation： cellular and molecular mechanisms[J]. Liver Int, 2019, 39(5)： 788-801.
9	Dugbartey GJ. Cellular and molecular mechanisms of cell damage and cell death in ischemia-reperfusion injury in organ transplantation[J].Mol Biol Rep, 2024, 51(1)： 473.
10	Luo Y, Zhou S, Xu T, et al. SENP2-mediated SERCA2a deSUMOylation increases calcium overload in cardiomyocytes to aggravate myocardial ischemia/reperfusion injury[J]. Chin Med J(Engl), 2023, 136(20)： 2496-2507.
11	Bigham NP, Wilson JJ. Metal coordination complexes as therapeutic agents for ischemia-reperfusion injury[J]. J Am Chem Soc, 2023,145(17)： 9389-9409.
12	Newton K, Strasser A, Kayagaki N, et al. Cell death[J]. Cell,2024, 187(2)： 235-256.
13	Bertheloot D, Latz E, Franklin BS. Necroptosis, pyroptosis and apoptosis： an intricate game of cell death[J]. Cell Mol Immunol,2021, 18(5)： 1106-1121.
14	Thomas K, Zondler L, Ludwig N, et al. Glutamine prevents acute kidney injury by modulating oxidative stress and apoptosis in tubular epithelial cells[J]. JCI Insight, 2022, 7(21)：e163161.
15	Li F, Mao Q, Wang J, et al. Salidroside inhibited cerebral ischemia/reperfusion-induced oxidative stress and apoptosis via Nrf2/Trx1 signaling pathway[J]. Metab Brain Dis, 2022,37(8)：2965-2978.
16	D'Arcy MS. Cell death： a review of the major forms of apoptosis,necrosis and autophagy[J]. Cell Biol Int, 2019, 43(6)： 582-592.
17	Bock FJ, Tait SWG. Mitochondria as multifaceted regulators of cell death[J]. Nat Rev Mol Cell Biol, 2020,21(2)：85-100.
18	Qi Y, Hu M, Wang Z, et al. Mitochondrial iron regulation as an emerging target in ischemia/reperfusion injury during kidney transplantation[J]. Biochem Pharmacol, 2023, 215： 115725.
19	Kaltenmeier C, Wang R, Popp B, et al. Role of immunoinflammatory signals in liver ischemia-reperfusion injury[J]. Cells,2022, 11(14)：2222.
20	Saeed WK, Jun DW, Jang K, et al. Does necroptosis have a crucial role in hepatic ischemia-reperfusion injury?[J]. PLoS One, 2017,12(9)： e0184752.
21	Chen X, Zhu R, Zhong J, et al. Mosaic composition of RIP1-RIP3 signalling hub and its role in regulating cell death[J]. Nat Cell Biol,2022, 24(4)： 471-482.
22	Tong X, Tang R, Xiao M, et al. Targeting cell death pathways for cancer therapy： recent developments in necroptosis, pyroptosis,ferroptosis, and cuproptosis research[J]. J Hematol Oncol, 2022,15(1)： 174.
23	Decuypere JP, Ceulemans LJ, Agostinis P, et al. Autophagy and the kidney： implications for ischemia-reperfusion injury and therapy[J]. Am J Kidney Dis, 2015, 66(4)： 699-709.
24	Li CJ, Liao WT, Wu MY, et al. New insights into the role of autophagy in tumor immune microenvironment[J]. Int J Mol Sci,2017, 18(7)：1566.
25	Kesavardhana S, Malireddi RKS, Kanneganti TD. Caspases in cell death, inflammation, and pyroptosis[J]. Annu Rev Immunol, 2020,38： 567-595.
26	Zhao H, Yang Y, Si X, et al. The role of pyroptosis and autophagy in ischemia reperfusion injury[J]. Biomolecules, 2022, 12(7)：1010.
27	Smith SF, Hosgood SA, Nicholson ML. Ischemia-reperfusion injury in renal transplantation： 3 key signaling pathways in tubular epithelial cells[J]. Kidney Int, 2019, 95(1)： 50-56.
28	Lasorsa F, Rutigliano M, Milella M, et al. Ischemia-reperfusion injury in kidney transplantation：mechanisms and potential therapeutic targets[J]. Int J Mol Sci, 2024, 25(8)：4332.
29	Santarsiero D, Aiello S. The complement system in kidney transplantation[J]. Cells, 2023, 12(5)：791.
30	Tang SP, Mao XL, Chen YH, et al. Reactive oxygen species induce fatty liver and ischemia-reperfusion injury by promoting inflammation and cell death[J]. Front Immunol, 2022, 13： 870239.
31	Granata S, La Russa D, Stallone G, et al. Inflammasome pathway in kidney transplantation[J]. Front Med (Lausanne), 2023, 10：1303110.
32	Lv S, Liu H, Wang H. The interplay between autophagy and NLRP3 inflammasome in ischemia/reperfusion injury[J]. Int J Mol Sci,2021, 22(16)：8773.
33	Huang G, Bao J, Shao X, et al. Inhibiting pannexin-1 alleviates sepsis-induced acute kidney injury via decreasing NLRP3 inflammasome activation and cell apoptosis[J]. Life Sci, 2020, 254： 117791.
34	Jia Y, Cui R, Wang C, et al. Metformin protects against intestinal ischemia-reperfusion injury and cell pyroptosis via TXNIP-NLRP3-GSDMD pathway[J]. Redox Biol, 2020, 32： 101534.
35	Su X, Liu B, Wang S, et al. NLRP3 inflammasome： a potential therapeutic target to minimize renal ischemia/reperfusion injury during transplantation[J]. Transpl Immunol, 2022, 75： 101718.
36	Jadlowiec CC, Frasco P, Macdonough E, et al. Association of DGF and early readmissions on outcomes following kidney transplantation[J]. Transpl Int, 2022, 35： 10849.
37	Puttarajappa CM, Jorgensen D, Yabes JG, et al. Trends and impact on cold ischemia time and clinical outcomes using virtual crossmatch for deceased donor kidney transplantation in the United States[J].Kidney Int, 2021, 100(3)： 660-671.
38	Andras I, Piana A, Verri P, et al. Systematic review of techniques and devices used to avoid warm ischemia time injury during kidney transplantation[J]. World J Urol, 2023, 41(4)： 993-1003.
39	Barba J, Zudaire JJ, Robles JE, et al. Is there a safe cold ischemia time interval for the renal graft?[J]. Actas Urol Esp, 2011,35(8)：475-480.
40	Benichou G, Yamada Y, Yun SH, et al. Immune recognition and rejection of allogeneic skin grafts[J]. Immunotherapy, 2011, 3(6)：757-770.
41	Zhou H, Lu H, Sun L, et al. Diagnostic biomarkers and immune infiltration in patients with T cell-mediated rejection after kidney transplantation[J]. Front Immunol, 2021, 12： 774321.
42	Liu Y, Pu X, Qin X, et al. Neutrophil extracellular traps regulate HMGB1 translocation and kupffer cell M1 polarization during acute liver transplantation rejection[J]. Front Immunol, 2022, 13： 823511.
43	Brenner BM, Lawler EV, Mackenzie HS. The hyperfiltration theory：a paradigm shift in nephrology[J]. Kidney Int, 1996,49(6)：1774-1777.
44	Helal I, Fick-Brosnahan GM, Reed-Gitomer B, et al. Glomerular hyperfiltration： definitions, mechanisms and clinical implications[J].Nat Rev Nephrol, 2012, 8(5)： 293-300.
45	Chen J, Layton AT, Edwards A. A mathematical model of O₂ transport in the rat outer medulla. I. Model formulation and baseline results[J]. Am J Physiol Renal Physiol, 2009, 297(2)： F517-F536.
46	Molitoris BA, Sutton TA. Endothelial injury and dysfunction： role in the extension phase of acute renal failure[J]. Kidney Int, 2004, 66(2)： 496-499.
47	Legrand M, Mik EG, Johannes T, et al. Renal hypoxia and dysoxia after reperfusion of the ischemic kidney[J]. Mol Med, 2008, 14(7-8)： 502-516.
48	魏军军, 楼仲冠, 楼江涌, 等. 慢性移植肾间质纤维化的发病机制及其治疗的研究进展[J]. 中华器官移植杂志, 2017, 38(11)：699-703.
49	Nickerson PW. Rationale for the IMAGINE study for chronic active antibody-mediated rejection (caAMR) in kidney transplantation[J].Am J Transplant, 2022, 22 Suppl 4： 38-44.
50	Norman JT, Clark IM, Garcia PL. Hypoxia promotes fibrogenesis in human renal fibroblasts[J]. Kidney Int, 2000, 58(6)： 2351-2366.
51	Zhang M, Liu Q, Meng H, et al. Ischemia-reperfusion injury：molecular mechanisms and therapeutic targets[J]. Signal Transduct Target Ther, 2024, 9(1)： 12.
52	Dufour L, Ferhat M, Robin A, et al. Ischemia-reperfusion injury after kidney transplantation[J]. Nephrol Ther, 2020, 16(6)： 388-399.
53	Zheng J, Lan P, Li M, et al. Anti-Na⁺/K⁺-ATPase DR antibody attenuates UUO-induced renal fibrosis through inhibition of Na⁺/K⁺-ATPase α1-dependent HMGB1 release[J]. Int Immunopharmacol,2023, 116： 109826.
54	Yan X, Xun M, Dou X, et al. Activation of Na⁺-K⁺-ATPase with DRm217 attenuates oxidative stress-induced myocardial cell injury via closing Na⁺-K⁺-ATPase/Src/Ros amplifier[J]. Apoptosis, 2017,22(4)： 531-543.

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