移植肾纤维化的诊断和治疗优化方案

王浩钧; 孙泽家; 王玮

doi:10.3969/j.issn.1674-7445.2023156

移植肾纤维化的诊断和治疗优化方案

doi: 10.3969/j.issn.1674-7445.2023156

100020　北京，首都医科大学附属北京朝阳医院泌尿外科

基金项目: 北京市自然科学基金面上项目（7212040）

详细信息

作者简介:

通讯作者:
王玮（ORCID 0000-0003-2642-3338），Email：weiwang0920@163.com

中图分类号: R617, R692
计量
- 文章访问数: 258
- HTML全文浏览量: 201
- PDF下载量: 44
- 被引次数: 0
出版历程
- 收稿日期: 2023-08-15
- 录用日期: 2023-11-06
- 网络出版日期: 2023-11-30
- 刊出日期: 2024-01-11

Optimal diagnosis and treatment for renal allograft fibrosis

Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China

More Information

Corresponding author: Wang Wei, Email: weiwang0920@163.com

摘要

摘要: 移植肾纤维化是肾移植术后常见且严重的并发症之一，严重影响移植肾的功能和存活率，甚至可能导致器官衰竭和患者死亡。目前关于移植肾纤维化的研究非常复杂，包括免疫、缺血-再灌注损伤、感染、药物毒性等，移植肾纤维化的诊断和治疗依然极具挑战性。本文旨在总结当前研究的最新进展，深入探讨移植肾纤维化的成因以及最新的诊断和治疗方法。通过提高诊断的准确率和优化治疗方案，有望改善肾移植受者的预后，也将为临床医师更好地管理肾移植受者提供参考。
- 肾移植 /
- 并发症 /
- 肾纤维化 /
- 生物标志物 /
- 慢性排斥反应 /
- 免疫抑制 /
- 干细胞治疗 /
- 基因治疗
Abstract: Renal allograft fibrosis is one of the common and severe complications after kidney transplantation, which seriously affects the function and survival rate of renal allograft, and may even lead to organ failure and patient death. At present, the researches on renal allograft fibrosis are highly complicated, including immunity, ischemia-reperfusion injury, infection and drug toxicity, etc. The diagnosis and treatment of renal allograft fibrosis remain extremely challenging. In this article, the latest research progress was reviewed and the causes, novel diagnosis and treatment strategies for renal allograft fibrosis were investigated. By improving diagnostic accuracy and optimizing treatment regimen, it is expected to enhance clinical prognosis of kidney transplant recipients, aiming to provide reference for clinicians to deliver proper management for kidney transplant recipients.
- Kidney transplantation /
- Complication /
- Renal fibrosis /
- Biomarker /
- Chronic rejection /
- Immunosuppression /
- Stem cell therapy /
- Gene therapy

HTML全文

下载: 全尺寸图片幻灯片

参考文献(55)

[1]	MCDANIELS JM, SHETTY AC, KUSCU C, et al. Single nuclei transcriptomics delineates complex immune and kidney cell interactions contributing to kidney allograft fibrosis[J]. Kidney Int, 2023, 103(6): 1077-1092. DOI: 10.1016/j.kint.2023.02.018.
[2]	FENIG Y, SURESH S, ROCHON C. Long-term survival after kidney transplantation[J]. N Engl J Med, 2022, 386(5): 499. DOI: 10.1056/NEJMc2115207.
[3]	WOLFE RA, ROYS EC, MERION RM. Trends in organ donation and transplantation in the United States, 1999-2008[J]. Am J Transplant, 2010, 10(4 Pt 2): 961-972. DOI: 10.1111/j.1600-6143.2010.03021.x.
[4]	任滌非, 王於尘, 苗芸. 巨噬细胞在移植肾纤维化中的作用研究进展[J]. 器官移植, 2023, 14(5): 723-729. DOI: 10.3969/j.issn.1674-7445.2023084. REN DF, WANG YC, MIAO Y. Research progress on the role of macrophages in renal allograft fibrosis[J]. Organ Transplant, 2023, 14(5): 723-729. DOI: 10.3969/j.issn.1674-7445.2023084.
[5]	NANKIVELL BJ, BORROWS RJ, FUNG CL, et al. The natural history of chronic allograft nephropathy[J]. N Engl J Med, 2003, 349(24): 2326-2333. DOI: 10.1056/NEJMoa020009.
[6]	SARITAS T, KRAMANN R. Kidney allograft fibrosis: diagnostic and therapeutic strategies[J]. Transplantation, 2021, 105(10): e114-e130. DOI: 10.1097/TP.0000000000003678.
[7]	HEILMAN RL, SMITH ML, KURIAN SM, et al. Transplanting kidneys from deceased donors with severe acute kidney injury[J]. Am J Transplant, 2015, 15(8): 2143-2151. DOI: 10.1111/ajt.13260.
[8]	STEGALL MD, PARK WD, LARSON TS, et al. The histology of solitary renal allografts at 1 and 5 years after transplantation[J]. Am J Transplant, 2011, 11(4): 698-707. DOI: 10.1111/j.1600-6143.2010.03312.x.
[9]	SERÓN D, MORESO F, RAMÓN JM, et al. Protocol renal allograft biopsies and the design of clinical trials aimed to prevent or treat chronic allograft nephropathy[J]. Transplantation, 2000, 69(9): 1849-1855. DOI: 10.1097/00007890-200005150-00019.
[10]	MANNON RB, MATAS AJ, GRANDE J, et al. Inflammation in areas of tubular atrophy in kidney allograft biopsies: a potent predictor of allograft failure[J]. Am J Transplant, 2010, 10(9): 2066-2073. DOI: 10.1111/j.1600-6143.2010.03240.x.
[11]	SHIMIZU T, TOMA H, HAYAKAWA N, et al. Clinical and pathological analyses of interstitial fibrosis and tubular atrophy cases after kidney transplantation[J]. Nephrology (Carlton), 2016, 21(Suppl 1): 26-30. DOI: 10.1111/nep.12766.
[12]	MENON MC, CHUANG PY, LI Z, et al. Intronic locus determines SHROOM3 expression and potentiates renal allograft fibrosis[J]. J Clin Invest, 2015, 125(1): 208-221. DOI: 10.1172/JCI76902.
[13]	MOORE J, MCKNIGHT AJ, SIMMONDS MJ, et al. Association of caveolin-1 gene polymorphism with kidney transplant fibrosis and allograft failure[J]. JAMA, 2010, 303(13): 1282-1287. DOI: 10.1001/jama.2010.356.
[14]	LIU X, LIU K, GUI Z, et al. Single nucleotide polymorphisms of IL-33 gene correlated with renal allograft fibrosis in kidney transplant recipients[J]. J Immunol Res, 2021: 8029180. DOI: 10.1155/2021/8029180.
[15]	LIANG H, XU F, WEN XJ, et al. Interleukin-33 signaling contributes to renal fibrosis following ischemia reperfusion[J]. Eur J Pharmacol, 2017, 812: 18-27. DOI: 10.1016/j.ejphar.2017.06.031.
[16]	YUAN PP, LI M, ZHANG Q, et al. 2-phenylacetamide separated from the seed of lepidium apetalum willd. inhibited renal fibrosis via MAPK pathway mediated RAAS and oxidative stress in SHR rats[J]. BMC Complement Med Ther, 2023, 23(1): 207. DOI: 10.1186/s12906-023-04012-w.
[17]	EPSTEIN M, KOVESDY CP, CLASE CM, et al. Aldosterone, mineralocorticoid receptor activation, and CKD: a review of evolving treatment paradigms[J]. Am J Kidney Dis, 2022, 80(5): 658-666. DOI: 10.1053/j.ajkd.2022.04.016.
[18]	YUAN X, WANG X, LI Y, et al. Aldosterone promotes renal interstitial fibrosis via the AIF-1/Akt/mTOR signaling pathway[J]. Mol Med Rep, 2019, 20(5): 4033-4044. DOI: 10.3892/mmr.2019.10680.
[19]	QIANG P, HAO J, YANG F, et al. Esaxerenone inhibits the macrophage-to-myofibroblast transition through mineralocorticoid receptor/TGF-β₁ pathway in mice induced with aldosterone[J]. Front Immunol, 2022, 13: 948658. DOI: 10.3389/fimmu.2022.948658.
[20]	VALENTIJN FA, KNOPPERT SN, MARQUEZ-EXPOSITO L, et al. Cellular communication network 2 (connective tissue growth factor) aggravates acute DNA damage and subsequent DNA damage response-senescence-fibrosis following kidney ischemia reperfusion injury[J]. Kidney Int, 2022, 102(6): 1305-1319. DOI: 10.1016/j.kint.2022.06.030.
[21]	KNOPS N, RAMAZANI Y, DE LOOR H, et al. Tacrolimus induces a pro-fibrotic response in donor-derived human proximal tubule cells dependent on common variants of the CYP3A5 and ABCB1 genes[J]. Nephrol Dial Transplant, 2023, 38(3): 599-609. DOI: 10.1093/ndt/gfac237.
[22]	UME AC, WENEGIEME TY, SHELBY JN, et al. Tacrolimus induces fibroblast-to-myofibroblast transition via a TGF-β-dependent mechanism to contribute to renal fibrosis[J]. Am J Physiol Renal Physiol, 2023, 324(5): F433-F445. DOI: 10.1152/ajprenal.00226.2022.
[23]	LIU L, GUO J, PANG XL, et al. Exploration of the mechanism of NORAD activation of TGF-β₁/Smad3 through miR-136-5p and promotion of tacrolimus-induced renal fibrosis[J]. Ren Fail, 2023, 45(1): 2147083. DOI: 10.1080/0886022X.2022.2147083.
[24]	BEN-DOV IZ, MUTHUKUMAR T, MOROZOV P, et al. MicroRNA sequence profiles of human kidney allografts with or without tubulointerstitial fibrosis[J]. Transplantation, 2012, 94(11): 1086-1094. DOI: 10.1097/TP.0b013e3182751efd.
[25]	ISHII Y, SAWADA T, KUBOTA K, et al. Injury and progressive loss of peritubular capillaries in the development of chronic allograft nephropathy[J]. Kidney Int, 2005, 67(1): 321-332. DOI: 10.1111/j.1523-1755.2005.00085.x.
[26]	LOUZADA RA, CORRE R, AMEZIANE EL HASSANI R, et al. NADPH oxidase DUOX1 sustains TGF-β₁ signalling and promotes lung fibrosis[J]. Eur Respir J, 2021, 57(1): 1901949. DOI: 10.1183/13993003.01949-2019.
[27]	SHI Y, TAO M, CHEN H, et al. Ubiquitin-specific protease 11 promotes partial epithelial-to-mesenchymal transition by deubiquitinating the epidermal growth factor receptor during kidney fibrosis[J]. Kidney Int, 2023, 103(3): 544-564. DOI: 10.1016/j.kint.2022.11.027.
[28]	HEYLEN L, THIENPONT B, BUSSCHAERT P, et al. Age-related changes in DNA methylation affect renal histology and post-transplant fibrosis[J]. Kidney Int, 2019, 96(5): 1195-1204. DOI: 10.1016/j.kint.2019.06.018.
[29]	BROOK NR, WHITE SA, WALLER JR, et al. Fibrosis-associated gene expression in renal transplant glomeruli after acute renal allograft rejection[J]. Br J Surg, 2003, 90(8): 1009-1014. DOI: 10.1002/bjs.4133.
[30]	PONTICELLI C, CAMPISE MR. The inflammatory state is a risk factor for cardiovascular disease and graft fibrosis in kidney transplantation[J]. Kidney Int, 2021, 100(3): 536-545. DOI: 10.1016/j.kint.2021.04.016.
[31]	SAYIN B, CANVER B, GURLEK DEMIRCI B, et al. Renin-angiotensin system blockage and avoiding high doses of calcineurin inhibitors prevent interstitial fibrosis and tubular atrophy in kidney transplant recipients[J]. Exp Clin Transplant, 2017, 15(Suppl 1): 32-36. DOI: 10.6002/ect.mesot2016.O19.
[32]	AKBARI A, FERGUSSON D, KOKOLO MB, et al. Spot urine protein measurements in kidney transplantation: a systematic review of diagnostic accuracy[J]. Nephrol Dial Transplant, 2014, 29(4): 919-926. DOI: 10.1093/ndt/gft520.
[33]	OLSON JD, TOOZE JA, BOURLAND DJ, et al. Measurement of renal cortical fibrosis by CT scan[J]. Res Diagn Interv Imaging, 2023, 5: 100024. DOI: 10.1016/j.redii.2023.100024.
[34]	HUA C, QIU L, ZHOU L, et al. Value of multiparametric magnetic resonance imaging for evaluating chronic kidney disease and renal fibrosis[J]. Eur Radiol, 2023, 33(8): 5211-5221. DOI: 10.1007/s00330-023-09674-1.
[35]	MAO W, DING X, DING Y, et al. Evaluation of interstitial fibrosis in chronic kidney disease by multiparametric functional MRI and histopathologic analysis[J]. Eur Radiol, 2023, 33(6): 4138-4147. DOI: 10.1007/s00330-022-09329-7.
[36]	徐小龙, 刘丁, 刘永光, 等. 慢性移植肾纤维化诊断的研究进展[J]. 广东医学, 2014, 35(19): 3094-3096. XU XL, LIU D, LIU YG, et al. Research progress in the diagnosis of chronic transplanted kidney fibrosis[J]. Guangdong Med, 2014, 35(19): 3094-3096.
[37]	HUANG R, FU P, MA L. Kidney fibrosis: from mechanisms to therapeutic medicines[J]. Signal Transduct Target Ther, 2023, 8(1): 129. DOI: 10.1038/s41392-023-01379-7.
[38]	王子杰. 肾移植后肾间质纤维化的诊断及治疗[J]. 肾脏病与透析肾移植杂志, 2014, 23(3): 279-282. WANG ZJ. Diagnosis and treatment of renal interstitial fibrosis after kidney transplantation[J]. Chin J Nephrol Dial Transplant, 2014, 23(3): 279-282.
[39]	NANKIVELL BJ, BORROWS RJ, FUNG CL, et al. Delta analysis of posttransplantation tubulointerstitial damage[J]. Transplantation, 2004, 78(3): 434-441. DOI: 10.1097/01.tp.0000128613.74683.d9.
[40]	CHEN L, LI X, DENG Y, et al. The PI3K-Akt-mTOR pathway mediates renal pericyte-myofibroblast transition by enhancing glycolysis through HKII[J]. J Transl Med, 2023, 21(1): 323. DOI: 10.1186/s12967-023-04167-7.
[41]	NISHIOKA S, ISHIMURA T, ENDO T, et al. Suppression of allograft fibrosis by regulation of mammalian target of rapamycin-related protein expression in kidney-transplanted recipients treated with everolimus and reduced tacrolimus[J]. Ann Transplant, 2021, 26: e926476. DOI: 10.12659/AOT.926476.
[42]	UME AC, WENEGIEME TY, WILLIAMS CR. Calcineurin inhibitors: a double-edged sword[J]. Am J Physiol Renal Physiol, 2021, 320(3): F336-F341. DOI: 10.1152/ajprenal.00262.2020.
[43]	SHIGEMATSU T, TAJIMA S, FU R, et al. The mTOR inhibitor everolimus attenuates tacrolimus-induced renal interstitial fibrosis in rats[J]. Life Sci, 2022, 288: 120150. DOI: 10.1016/j.lfs.2021.120150.
[44]	BARRERA-CHIMAL J, ESTRELA GR, LECHNER SM, et al. The myeloid mineralocorticoid receptor controls inflammatory and fibrotic responses after renal injury via macrophage interleukin-4 receptor signaling[J]. Kidney Int, 2018, 93(6): 1344-1355. DOI: 10.1016/j.kint.2017.12.016.
[45]	ZHANG Y, NAKANO D, GUAN Y, et al. A sodium-glucose cotransporter 2 inhibitor attenuates renal capillary injury and fibrosis by a vascular endothelial growth factor-dependent pathway after renal injury in mice[J]. Kidney Int, 2018, 94(3): 524-535. DOI: 10.1016/j.kint.2018.05.002.
[46]	王珍, 曹博宁, 侯金易. 肾纤维化的治疗[J]. 家庭医学, 2022(6): 9-11. WANG Z, CAO BN, HOU JY. Treatment of renal fibrosis[J]. Fam Med, 2022(6): 9-11.
[47]	SUGIMOTO H, LEBLEU VS, BOSUKONDA D, et al. Activin-like kinase 3 is important for kidney regeneration and reversal of fibrosis[J]. Nat Med, 2012, 18(3): 396-404. DOI: 10.1038/nm.2629.
[48]	INOTANI S, TANIGUCHI Y, NAKAMURA K, et al. Knockout of Zeb2 ameliorates progression of renal tubulointerstitial fibrosis in a mouse model of renal ischemia-reperfusion injury[J]. Nephrol Dial Transplant, 2022, 37(3): 454-468. DOI: 10.1093/ndt/gfab311.
[49]	SHATI AA, ALKABLI J, ALFAIFI MY, et al. Comparison of the ameliorative roles of crab chitosan nanoparticles and mesenchymal stem cells against cisplatin-triggered nephrotoxicity[J]. Int J Biol Macromol, 2023, 242(Pt 4): 124985. DOI: 10.1016/j.ijbiomac.2023.124985.
[50]	CIANCI R, SIMEONI M, CIANCI E, et al. Stem cells in kidney ischemia: from inflammation and fibrosis to renal tissue regeneration[J]. Int J Mol Sci, 2023, 24(5): 4631. DOI: 10.3390/ijms24054631.
[51]	LI S, WANG Y, WANG Z, et al. Enhanced renoprotective effect of GDNF-modified adipose-derived mesenchymal stem cells on renal interstitial fibrosis[J]. Stem Cell Res Ther, 2021, 12(1): 27. DOI: 10.1186/s13287-020-02049-z.
[52]	MATHEW AP, UTHAMAN S, BAE EH, et al. Vimentin targeted nano-gene carrier for treatment of renal diseases[J]. J Korean Med Sci, 2021, 36(49): e333. DOI: 10.3346/jkms.2021.36.e333.
[53]	TANG TT, WANG B, LI ZL, et al. Kim-1 targeted extracellular vesicles: a new therapeutic platform for RNAi to treat AKI[J]. J Am Soc Nephrol, 2021, 32(10): 2467-2483. DOI: 10.1681/ASN.2020111561.
[54]	XIE ZY, DONG W, ZHANG L, et al. NFAT inhibitor 11R-VIVIT ameliorates mouse renal fibrosis after ischemia-reperfusion-induced acute kidney injury[J]. Acta Pharmacol Sin, 2022, 43(8): 2081-2093. DOI: 10.1038/s41401-021-00833-y.
[55]	ZHAO H, LUO X, ZHOU Z, et al. Early treatment with xenon protects against the cold ischemia associated with chronic allograft nephropathy in rats[J]. Kidney Int, 2014, 85(1): 112-123. DOI: 10.1038/ki.2013.334.