2025年中国肾移植领域研究大盘点

Research highlights on kidney transplantation in 2025 from China

摘要

肾移植是治疗终末期肾病的首选方案，但供器官短缺、移植物损伤及排斥反应仍是制约其长期疗效的瓶颈。2025年，肾移植领域在基础与临床研究方面均取得了突破性进展。在供者来源拓展方面，多基因修饰猪异种移植在非人灵长类模型中实现长效存活，酶转化法构建“通用O型供肾”更是打破了ABO血型不相容移植的壁垒。在移植物损伤机制与保护方面，研究深入揭示了缺血-再灌注损伤中核磷酸蛋白1乳酸化驱动铁死亡及代谢重编程的分子机制，并开发了基于纳米载体与间充质干细胞外泌体的精准干预策略。在排斥反应诊疗方面，单细胞转录组测序精细绘制了包含Isg15⁺巨噬细胞在内的免疫应答图谱，功能性MRI与靶向成纤维细胞活化蛋白分子影像技术显著提升了排斥反应的无创监测效能。此外，基于药物基因组学的个体化免疫抑制方案及针对各类并发症的综合防治策略，进一步优化了受者的全生命周期管理。本文对2025年我国团队在肾移植领域相关的研究进展进行系统梳理和阐述，旨在为临床实践及未来科研方向提供参考。

Abstract

Kidney transplantation is the first-line treatment for end-stage renal disease. However, the shortage of donor organs, graft injury and rejection remain major bottlenecks restricting its long-term efficacy. In 2025, breakthrough advances have been achieved in both basic and clinical research in the field of kidney transplantation. In terms of expanding donor sources, multi-gene-modified porcine xenotransplantation have achieved long-term survival in non-human primate models, and the construction of "universal type O donor kidneys" via enzymatic conversion has broken through the barrier of ABO-incompatible transplantation. Regarding the mechanisms and protection of graft injury, studies have deeply elucidated the molecular mechanism by which lactylation of nucleophosmin 1 drives ferroptosis and metabolic reprogramming during ischemia-reperfusion injury, and precise intervention strategies based on nanocarriers and mesenchymal stem cell-derived exosomes have been developed. In the diagnosis and treatment of rejection, single-cell RNA sequencing has finely mapped the immune response landscape including Isg15 ⁺ macrophages, and functional MRI as well as molecular imaging targeting fibroblast activation protein have significantly improved the efficacy of non-invasive monitoring of rejection. In addition, individualized immunosuppressive regimens based on pharmacogenomics and comprehensive prevention and treatment strategies for various complications have further optimized the whole-life-cycle management of transplant recipients. This article systematically reviews and summarizes the research progress made by Chinese teams in renal transplantation in 2025, aiming to provide references for clinical practice and future research directions.

关键词

肾移植 / 异种移植 / 基因修饰猪 / 缺血-再灌注损伤 / ABO血型不相容 / 排斥反应 / 铁死亡 / 精准医学

Key words

Kidney transplantation / Xenotransplantation / Genetically modified pig / Ischemia-reperfusion injury / ABO incompatibility / Rejection / Ferroptosis / Precision medicine

参考文献

[1] ZENG J, MA M, TAO Z, et al. Enzyme-converted O kidneys allow ABO-incompatible transplantation without hyperacute rejection in a human decedent model[J]. Nat Biomed Eng, 2026, 10(6): 1154-1170. DOI: 10.1038/s41551-025-01513-6.

[2] JIANG H, JIANG H, HE S, et al. Antibodies to unknown antigens other than swine leukocyte antigens on GTKO/β4GalNT2KO pig cells are associated with AHXR after pig-to-rhesus monkey kidney transplantation[J]. Front Immunol, 2025, 16: 1663702. DOI: 10.3389/fimmu.2025.1663702.

[3] XU K, ZHAO H, JIA B, et al. Specific pathogen free ten gene-edited donor pigs for xenotransplantation[J]. Protein Cell, 2025, 16(12): 1002-1016. DOI: 10.1093/procel/pwaf075.

[4] MA S, QI R, HAN S, et al. Plasma exchange and intravenous immunoglobulin prolonged the survival of a porcine kidney xenograft in a sensitized, brain-dead human recipient[J]. Chin Med J, 2025, 138(18): 2293-2307. DOI: 10.1097/CM9.0000000000003338.

[5] YU H, YIN H, MEI Y, et al. Nucleophosmin 1 lactylation in graft kidney induces ferroptotic trigger waves that exacerbate delayed graft function[J]. Nat Commun, 2025, 17(1): 277. DOI: 10.1038/s41467-025-66991-3.

[6] WU Z, YU B, HE Q, et al. LCN2 drives ferroptosis-associated ischemia-reperfusion injury after renal transplantation: integrated machine learning and in vivo validation[J]. Apoptosis, 2025, 30(11/12): 3026-3043. DOI: 10.1007/s10495-025-02182-1.

[7] HU Q, LU Z, YASEN K, et al. Nano-self-assembled particles loaded with aldehyde dehydrogenase 2 agonist inhibit ischemia-reperfusion injury of transplanted kidneys[J]. ACS Nano, 2025, 19(40): 35853-35870. DOI: 10.1021/acsnano.5c12681.

[8] LIAO Z, CHEN G, LIU K, et al. One-stop early noninvasive evaluation of renal allograft rejection and fibrosis: microstructural mapping via time-dependent diffusion MRI[J]. EBioMedicine, 2025, 122: 106034. DOI: 10.1016/j.ebiom.2025.106034.

[9] WEI F, WANG Z, QI R, et al. Single-cell transcriptomics unravels the early immune landscape of renal allograft rejection and nominates Ccl3-Ccr5 as a therapeutic target[J]. Front Immunol, 2025, 16: 1663251. DOI: 10.3389/fimmu.2025.1663251.

[10] WANG Z, WEI F, HUANG D, et al. Visualizing early allograft rejection: an M1 macrophage-specific GLUT1 probe predicts TCMR onset in renal transplantation[J]. Front Immunol, 2025, 16: 1670370. DOI: 10.3389/fimmu.2025.1670370.

[11] LUO S, XU M, SHEN R, et al. Noninvasive diagnosis and classification of kidney transplantation rejection by (18)F-FAPI-04 PET/CT[J]. Eur J Nucl Med Mol Imaging, 2025, 52(12): 4685-4695. DOI: 10.1007/s00259-025-07307-x.

[12] YANG W, XIA R, ZHAO P, et al. Impact of high tacrolimus exposure on graft function and development of a prediction model in kidney transplant recipients: a single-center retrospective cohort study[J]. Drug Des Devel Ther, 2025, 19: 12035-12047. DOI: 10.2147/DDDT.S560652.

[13] CHEN H, LI C, OU S, et al. The impact of pharmacists' interventions within the closed loop immunosuppressant management process on kidney transplant recipients: a retrospective cohort study[J]. Front Immunol, 2025, 16: 1553786. DOI: 10.3389/fimmu.2025.1553786.

[14] YEN F S, HSU C C, YEH Y K, et al. The impact of sodium-glucose cotransporter-2 inhibitors on dialysis risk and mortality in kidney transplant patients with diabetes[J]. Am J Transplant, 2025, 25(9): 1954-1964. DOI: 10.1016/j.ajt.2025.03.019.

[15] ZENG J, MA M, JIANG X, et al. Enzymatic conversion of blood group B kidney prevents hyperacute antibody-mediated injuries in ABO-incompatible transplantation[J]. Nat Commun, 2025, 16(1): 1506. DOI: 10.1038/s41467-025-56563-w.

[16] MA M, HAN F, LENG Q, et al. Preoperative donor urinary UDP-Glc as an independent risk factor for delayed graft function[J]. Front Immunol, 2025, 16: 1545280. DOI: 10.3389/fimmu.2025.1545280.

[17] LENG Q, MA M, TANG Z, et al. Assessing donor kidney function: the role of CIRBP in predicting delayed graft function post-transplant[J]. Front Immunol, 2025, 15: 1518279. DOI: 10.3389/fimmu.2024.1518279.

[18] YIN S, TANG Y, ZHU M, et al. Ex vivo surgical removal versus conservative management of small asymptomatic kidney stones in living donors and long-term kidney transplant outcomes[J]. Transplantation, 2025, 109(3): e175-e183. DOI: 10.1097/TP.0000000000005146.

[19] YIN S, LI X, LIANG C, et al. Evaluation of early donor renal function recovery after living-donor nephrectomy as a predictor of allograft failure after kidney transplantation: a longitudinal cohort and machine learning study[J]. EClinicalMedicine, 2025, 84: 103278. DOI: 10.1016/j.eclinm.2025.103278.

[20] HE G, XI Y, JIANG X, et al. Comparison of survival outcomes between kidney transplant and dialysis in patients with previous cancer[J]. Chin Med J, 2026, 139(10): 1521-1531. DOI: 10.1097/CM9.0000000000003700.

[21] WANG T, LI N, ZHAO Z, et al. Microplastic contamination in kidney transplant donor tissues and its association with early post-transplant blood pressure changes in recipients: a multi-modal analytical study[J]. J Hazard Mater, 2025, 497: 139728. DOI: 10.1016/j.jhazmat.2025.139728.

[22] QIAN Z, ZHANG X, HUANG J, et al. Glucose deprivation-restoration induces labile iron overload and ferroptosis in renal tubules through V-ATPase-mTOR axis-mediated ferritinophagy and iron release by TPC2[J]. Free Radic Biol Med, 2025, 236: 204-219. DOI: 10.1016/j.freeradbiomed.2025.05.390.

[23] PENG X, XIE Y, PAN H, et al. Dietary methionine deprivation enhances renal resilience against ischemia-reperfusion injury in mice through modulation of glucose oxidation[J]. Commun Biol, 2026, 9: 169. DOI: 10.1038/s42003-025-09447-0.

[24] YI W, SONG L, CHEN Z. Methionine restriction attenuates renal injury by suppressing macrophage polarization via IRF1 downregulation[J]. Food Funct, 2025, 16(22): 8819-8826. DOI: 10.1039/d5fo04229a.

[25] QI Y, WANG Z, ZHANG Z, et al. Iron supplementation protects against renal ischemia-reperfusion injury by enhancing mitochondrial respiratory complex assembly[J]. Biochem Pharmacol, 2025, 241: 117197. DOI: 10.1016/j.bcp.2025.117197.

[26] HU Q, CHEN H, LAN J N, et al. KLF10 induced by hypothermic machine perfusion alleviates renal inflammation through BIRC2/noncanonical NF-κB pathway[J]. Transplantation, 2025, 109(6): e273-e286. DOI: 10.1097/TP.0000000000005314.

[27] LI S, DUAN F, QIU Z, et al. Polymer-conjugated SOD-Pt0 micelles enhance ROS cascade scavenging to alleviate ischemia-reperfusion injury during kidney transplantation[J]. Adv Healthc Mater, 2025, 14(16): e2500696. DOI: 10.1002/adhm.202500696.

[28] ZHAO X, LI X, HE L, et al. Engineered Needlepatch for the treatment of acute kidney injury[J]. Biomaterials, 2026, 329: 123936. DOI: 10.1016/j.biomaterials.2025.123936.

[29] MA M, ZENG J, ZHU M, et al. Human umbilical cord mesenchymal stem cells-derived extracellular vesicles ameliorate kidney ischemia-reperfusion injury by suppression of senescent tubular epithelial cells: experimental study[J]. Int J Surg, 2025, 111(1): 394-410. DOI: 10.1097/JS9.0000000000002074.

[30] WU X, WU X, WANG Z, et al. Delivery of exogenous miR-19b by Wharton’s Jelly mesenchymal stem cells attenuates transplanted kidney ischemia/reperfusion injury by regulating cellular metabolism[J]. Drug Deliv Transl Res, 2025, 15(3): 925-938. DOI: 10.1007/s13346-024-01645-3.

[31] PENG J, WANG S, PAN X, et al. Identification of ALDH2 as a novel target for the treatment of acute kidney injury in kidney transplantation based on WGCNA and machine learning algorithms and exploration of its potential mechanism of action using animal experiments[J]. Front Immunol, 2025, 16: 1536800. DOI: 10.3389/fimmu.2025.1536800.

[32] ZHAO L, XU M, PFEFFERKORN A M, et al. Lipocalin-2 restores soluble guanylyl cyclase-dependent dilation of the afferent arteriole after renal transplantation or ex vivo hypoxia/reoxygenation in mice[J]. Acta Physiol, 2025, 241(8): e70077. DOI: 10.1111/apha.70077.

[33] XIAO H, ZHANG J, PANG Q, et al. Identification and characterization of senescent macrophages in renal allograft rejection: a cross-species MultiOmics study[J]. Front Immunol, 2025, 16: 1623124. DOI: 10.3389/fimmu.2025.1623124.

[34] SHEN Q, ZHU T, YAN S, et al. Macrophages mediate acute kidney allograft rejection via a toll-like receptor 4-dependent mechanism[J]. Kidney Int, 2025, 108(6): 1105-1122. DOI: 10.1016/j.kint.2025.09.014.

[35] NI B, YANG C, ZHANG J, et al. Rictor ameliorates acute antibody-mediated rejection following kidney transplantation by suppressing macrophage M1 polarization through p65-NLRP3 axis[J]. Adv Sci, 2025, 12(34): e17119. DOI: 10.1002/advs.202417119.

[36] ZHU T, SHEN Q, SHEN L, et al. Senescence-induced p21(high) macrophages contributed to CD8⁺ T cells-related immune hyporesponsiveness in kidney transplantation via Zfp36/IL-27 axis [J]. Cell Discov, 2025, 11(1): 38. DOI: 10.1038/s41421-025-00784-2.

[37] LU T, SONG H, HE L, et al. Targeted expansion of Treg cells to induce immune tolerance after kidney transplantation[J]. Adv Sci, 2026, 13(1): e07943. DOI: 10.1002/advs.202507943.

[38] LIU Y, FU Q, YANG M, et al. Downregulation of N6-methyladenosine (m6A) methylation of Sema4D mRNA contributes to Treg dysfunction and allograft rejection[J]. Am J Transplant, 2025, 25(5): 930-942. DOI: 10.1016/j.ajt.2025.01.017.

[39] HUANG Z, FENG Y, LIU X, et al. HLA-DQA1*03:02-DQB1*03:03 is the dominant immunogenic heterodimer for posttransplant HLA-DQ de novo DSA development in a cohort of Chinese kidney transplant patients[J]. Transplantation, 2026, 110(1): e266-e275. DOI: 10.1097/TP.0000000000005445.

[40] YU Y, BI Z, JIANG Q, et al. Oxidized ATP suppresses B lymphocyte activity to attenuate antibody-mediated rejection of kidney allografts in mice[J]. Transplantation, 2025, 109(1): e11-e21. DOI: 10.1097/TP.0000000000005118.

[41] WU D, YOU J, LIU H, et al. ScRNA profiling of peripheral blood in kidney transplant recipients across rejection responses and treatments[J]. Sci Data, 2026, 13: 171. DOI: 10.1038/s41597-025-06489-1.

[42] LIN L, CHEN T, YU S, et al. Normothermic machine perfusion combined with modified small interfering RNA targeting beta-2-microglobulin and class II major histocompatibility complex transactivator mitigates acute rejection of renal allograft[J]. Transplantation, 2026, 110(1): e154-e165. DOI: 10.1097/TP.0000000000005529.

[43] GUO Z, SA R, ZHAO G, et al. Case report: adjuvant splenic irradiation therapy effectively eliminates donor-specific antibodies and reverses refractory early active antibody-mediated rejection after presensitized kidney transplantation[J]. Front Immunol, 2025, 16: 1670507. DOI: 10.3389/fimmu.2025.1670507.

[44] XIANG Q, YANG Y, LI G, et al. Population pharmacokinetic/pharmacodynamic modeling of tacrolimus in renal transplant recipients: impact of CYP3A5 genotype and Wuzhi capsule co-medication[J]. Drug Des Devel Ther, 2025, 19: 8375-8389. DOI: 10.2147/DDDT.S542786.

[45] PENG L, LAI W, YU S, et al. GLP-1 and glucagon receptor dual agonism ameliorates kidney allograft fibrosis by improving lipid metabolism[J]. Front Immunol, 2025, 16: 1551136. DOI: 10.3389/fimmu.2025.1551136.

[46] HAN Q, NI B, BAO W, et al. CAV1 promotes epithelial-to-mesenchymal transition (EMT) and chronic renal allograft interstitial fibrosis by activating the ferroptosis pathway[J]. Front Immunol, 2025, 16: 1523855. DOI: 10.3389/fimmu.2025.1523855.

[47] YAO Q, ZHENG X, ZHANG X, et al. METTL3 potentiates M2 macrophage-driven MMT to aggravate renal allograft fibrosis via the TGF-β1/Smad3 pathway[J]. Adv Sci, 2025, 12(11): 2412123. DOI: 10.1002/advs.202412123.

[48] LIU Y, XU J S, CAO L, et al. CRISPR-based assays for the detection of BK virus and JC virus infections post-kidney transplantation[J]. Mil Med Res, 2025, 12(1): 44. DOI: 10.1186/s40779-025-00632-0.

[49] WU T, GUO F, YANG S, et al. A novel perspective on tubular C4d positivity in BK polyomavirus nephropathy[J]. Kidney Int Rep, 2025, 10(7): 2369-2383. DOI: 10.1016/j.ekir.2025.05.006.

[50] ZHONG L, TANG S, PU Z, et al. Impact of prophylactic cytomegalovirus immunoglobulin on cytomegalovirus viremia and graft function in ABO-incompatible living donor kidney transplantation: a retrospective analysis[J]. Front Immunol, 2025, 16: 1562951. DOI: 10.3389/fimmu.2025.1562951.

[51] HUANG J S, WANG H K, RONG L P, et al. Case report: maribavir for refractory cytomegalovirus viremia after renal transplantation in a child with Schimke’s immune-osseous dysplasia[J]. Front Immunol, 2025, 16: 1521763. DOI: 10.3389/fimmu.2025.1521763.

[52] CUI X, SITU J, TANG T, et al. Prevalence of Rocahepevirus ratti (rat hepatitis E virus) in humans and rats in China[J]. JHEP Rep, 2025, 7(5): 101370. DOI: 10.1016/j.jhepr.2025.101370.

[53] LI L, DANG G, DU F, et al. Construction and validation of a risk prediction model for hyperamylasemia after kidney transplantation[J]. Front Immunol, 2025, 16: 1675844. DOI: 10.3389/fimmu.2025.1675844.

[54] ZHOU Z, ZHANG L, ZHANG D, et al. High-level ePVS was accompanied by an increase in kidney transplant failure risk: analysis based on the MIMIC-IV database[J]. Front Immunol, 2025, 16: 1574525. DOI: 10.3389/fimmu.2025.1574525.

[55] XIAO Y F, YANG S F, HUANG S A, et al. FK506 binding protein 12.6-mediated inhibition of sperm-specific calcineurin is essential for FK506-induced male infertility by disturbing the homeostasis of calcium and mitochondria[J]. Mol Biomed, 2025, 6(1): 149. DOI: 10.1186/s43556-025-00391-3.

[56] FANG J, LIN X, WEI C, et al. Factors associated with dietary behaviour in kidney transplant recipients: a cross-sectional study[J]. Front Nutr, 2025, 12: 1467667. DOI: 10.3389/fnut.2025.1467667.

[57] WANG Z, GAO X, JI H, et al. Characterization of gut microbiota and metabolites in renal transplant recipients during COVID-19 and prediction of one-year allograft function[J]. J Transl Med, 2025, 23(1): 420. DOI: 10.1186/s12967-025-06090-5.

基金资助

国家自然科学基金面上项目(82270783)

国家自然科学基金面上项目(82271805)

广州市科技计划项目(2025A03J4431)

广州市科技计划项目(2023B03J1250)

非传染慢性疾病-国家科技重大专项项目(2025ZD0547500)