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中华肾病研究电子杂志 ›› 2025, Vol. 14 ›› Issue (02) : 91 -96. doi: 10.3877/cma.j.issn.2095-3216.2025.02.005

综述

肾小管间质纤维化生物标志物研究进展
张睿敏1, 董哲毅1,(), 王倩1, 陈香美1   
  1. 1. 100853 北京,解放军总医院第一医学中心肾脏病医学部、肾脏疾病全国重点实验室、国家慢性肾病临床医学研究中心、重症肾脏疾病器械与中西医药物研发北京市重点实验室、数智中医泛血管疾病防治北京市重点实验室、国家中医药管理局高水平中医药重点学科
  • 收稿日期:2024-03-12 出版日期:2025-04-28
  • 通信作者: 董哲毅
  • 基金资助:
    北京市自然科学基金(7252018,L222133,L232122)国家自然科学基金(62450131);北京市科技计划课题(Z221100007422121)首都卫生发展科研专项项目(CFH 2024-1-5021)

Research progress on biomarkers of renal tubulointerstitial fibrosis

Ruimin Zhang1, Zheyi Dong1,(), Qian Wang1, Xiangmei Chen1   

  1. 1. Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases,Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases, Beijing Key Laboratory of Digital Intelligent TCM for Prevention and Treatment of Pan-vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine (zyyzdxk-2023310), Beijing 100853, China
  • Received:2024-03-12 Published:2025-04-28
  • Corresponding author: Zheyi Dong
引用本文:

张睿敏, 董哲毅, 王倩, 陈香美. 肾小管间质纤维化生物标志物研究进展[J/OL]. 中华肾病研究电子杂志, 2025, 14(02): 91-96.

Ruimin Zhang, Zheyi Dong, Qian Wang, Xiangmei Chen. Research progress on biomarkers of renal tubulointerstitial fibrosis[J/OL]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2025, 14(02): 91-96.

肾小管间质纤维化是各类慢性肾脏病进展到终末期肾病的共同通路,其严重程度也是反映肾功能和预后的重要病理预测因子。随着肾小管间质纤维化的发生发展机制研究取得重大进展,越来越多的生物标志物被发现,并成为判断肾小管间质纤维化程度、具有早期诊断优势的新型辅助手段。本文旨在从肾脏病理特点和病理生理机制的角度,结合动物实验及临床研究结果,综述肾小管间质纤维化相关的血、尿生物标志物,为深入研究肾小管间质纤维化的早期无创诊断和肾脏疾病预后提供参考。

Renal tubulointerstitial fibrosis represents a universal pathway in the progression of various types of chronic kidney disease to end-stage renal disease, and its severity serves as a critical pathological predictor for renal function and prognosis. With significant progress in the study of the mechanism of occurrence and development of renal tubulointerstitial fibrosis, more and more biomarkers have been discovered and become a new auxiliary tool for judging the degree of renal tubulointerstitial fibrosis,showing early diagnostic advantages. This article aimed to review the blood and urine biomarkers related to renal tubulointerstitial fibrosis from the perspective of renal pathological characteristics and pathophysiological mechanisms combining with animal experiments and clinical research results, in order to provide reference for in-depth research on early and non-invasive diagnosis of renal tubulointerstitial fibrosis and the prognosis of kidney diseases.

表1 肾小管间质纤维化相关生物标志物
[1]
Saritas T, Kramann R. Kidney allograft fibrosis: diagnostic and therapeutic strategies [J]. Transplantation, 2021, 105(10):e114-e130.
[2]
Rende U, Guller A, Goldys EM, et al. Diagnostic and prognostic biomarkers for tubulointerstitial fibrosis [J]. J Physiol, 2023, 601(14): 2801-2826.
[3]
Ix JH, Shlipak MG. The promise of tubule biomarkers in kidney disease: a review [J]. Am J Kidney Dis, 2021, 78(5): 719-727.
[4]
张轶男, 朱国贞. 急性肾损伤向慢性肾脏病转变研究进展[J/OL]. 中华肾病研究电子杂志, 2024, 13(2): 106-112.
[5]
Fukata F, Eriguchi M, Tamaki H, et al. Differential impact of glomerular and tubule-interstitial histological changes on kidney outcome between non-proteinuric and proteinuric diabetic nephropathy [J]. Clin Exp Nephrol, 2024, 28(4): 282-292.
[6]
Huang R, Fu P, Ma L. Kidney fibrosis: from mechanisms to therapeutic medicines [J]. Signal Transduct Target Ther, 2023,8(1): 129.
[7]
Sun H, Zhao A, Li M, et al. Interaction of calcium binding protein S100A16 with myosin-9 promotes cytoskeleton reorganization in renal tubulointerstitial fibrosis [J]. Cell Death Dis, 2020, 11(2): 146.
[8]
Langewisch E, Mannon RB. Chronic allograft injury [J]. Clin J Am Soc Nephrol, 2021, 16(11): 1723-1729.
[9]
Genovese F, Boor P, Papasotiriou M, et al. Turnover of type III collagen reflects disease severity and is associated with progression and microinflammation in patients with IgA nephropathy [J].Nephrol Dial Transplant, 2016, 31(3): 472-479.
[10]
Papasotiriou M, Genovese F, Klinkhammer BM, et al. Serum and urine markers of collagen degradation reflect renal fibrosis in experimental kidney diseases [J]. Nephrol Dial Transplant,2015, 30(7): 1112-1121.
[11]
Bülow RD, Boor P. Extracellular matrix in kidney fibrosis: more than just a scaffold [J]. J Histochem Cytochem, 2019, 67(9):643-661.
[12]
Schmidt IM, Hall IE, Kale S, et al. Chitinase-like protein Brp-39/YKL-40 modulates the renal response to ischemic injury and predicts delayed allograft function [J]. J Am Soc Nephrol,2013, 24(2): 309-319.
[13]
Hijmans RS, Rasmussen DG, Yazdani S, et al. Urinary collagen degradation products as early markers of progressive renal fibrosis[J]. J Transl Med, 2017, 15(1): 63.
[14]
Nielsen PM, Mariager C, Rasmussen DGK, et al. Noninvasive assessment of fibrosis following ischemia/reperfusion injury in rodents utilizing Na magnetic resonance imaging [J].Pharmaceutics, 2020, 12(8): 775.
[15]
Mansour SG, Puthumana J, Coca SG, et al. Biomarkers for the detection of renal fibrosis and prediction of renal outcomes: a systematic review [J]. BMC Nephrol, 2017, 18(1): 72.
[16]
张磊, 金华, 王亿平, 等. 清肾颗粒对慢性肾衰竭患者肾功能及血清α-平滑肌动蛋白和E-钙粘蛋白的影响[J]. 南京中医药大学学报, 2019, 35(6): 651-654, 737.
[17]
Chun-Yan L, Zi-Yi Z, Tian-Lin Y, et al. Liquid biopsy biomarkers of renal interstitial fibrosis based on urinary exosome[J]. Exp Mol Pathol, 2018, 105(2): 223-228.
[18]
Hirohama D, Abedini A, Moon S, et al. Unbiased human kidney tissue proteomics identifies matrix metalloproteinase 7 as a kidney disease biomarker [J]. J Am Soc Nephrol, 2023, 34(7): 1279-1291.
[19]
Grandaliano G, Gesualdo L, Bartoli F, et al. MCP-1 and EGF renal expression and urine excretion in human congenital obstructive nephropathy [J]. Kidney Int, 2000, 58(1): 182-192.
[20]
Srivastava A, Schmidt IM, Palsson R, et al. The associations of plasma biomarkers of inflammation with histopathologic lesions,kidney disease progression, and mortality-the Boston kidney biopsy cohort study [J]. Kidney Int Rep, 2021, 6(3): 685-694.
[21]
Chen S, Zhang M, Li J, et al. β-catenin-controlled tubular cellderived exosomes play a key role in fibroblast activation via the OPN-CD44 axis [J]. J Extracell Vesicles, 2022, 11(3):e12203.
[22]
Lee YH, Seo JW, Kim M, et al. Urinary mRNA signatures as predictors of renal function decline in patients with biopsy-proven diabetic kidney disease [J]. Front Endocrinol (Lausanne),2021, 12: 774436.
[23]
Lee YH, Kim KP, Park SH, et al. Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease [J].Nephrol Dial Transplant, 2021, 36(2): 295-305.
[24]
Ou SM, Tsai MT, Chen HY, et al. Identification of galectin-3 as potential biomarkers for renal fibrosis by RNA-sequencing and clinicopathologic findings of kidney biopsy [J]. Front Med(Lausanne), 2021, 8: 748225.
[25]
Ou SM, Tsai MT, Chen HY, et al. Urinary galectin-3 as a novel biomarker for the prediction of renal fibrosis and kidney disease progression [J]. Biomedicines, 2022, 10(3): 585.
[26]
Basturk T, Ojalvo D, Mazi EE, et al. Pentraxin-2 is associated with renal fibrosis in patients undergoing renal biopsy [J].Clinics (Sao Paulo), 2020, 75: e1809.
[27]
Saejong S, Townamchai N, Somparn P, et al. MicroRNA-21 in plasma exosome, but not from whole plasma, as a biomarker for the severe interstitial fibrosis and tubular atrophy (IF/TA) in post-renal transplantation [J]. Asian Pac J Allergy Immunol,2022, 40(1): 94-102.
[28]
An Y, Zhang C, Xu F, et al. Increased urinary miR-196a level predicts the progression of renal injury in patients with diabetic nephropathy [J]. Nephrol Dial Transplant, 2020, 35(6):1009-1016.
[29]
Nariman-Saleh-Fam Z, Bastami M, Ardalan M, et al. Cell-free microRNA-148a is associated with renal allograft dysfunction:implication for biomarker discovery [J]. J Cell Biochem, 2019,120(4): 5737-5746.
[30]
Vanhove T, Kinashi H, Nguyen TQ, et al. Tubulointerstitial expression and urinary excretion of connective tissue growth factor 3 months after renal transplantation predict interstitial fibrosis and tubular atrophy at 5 years in a retrospective cohort analysis [J].Transpl Int, 2017, 30(7): 695-705.
[31]
Ju W, Nair V, Smith S, et al. Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker [J]. Sci Transl Med, 2015, 7(316):316ra193.
[32]
Zhao X, He X, Wei W, et al. USP22 aggravated diabetic renal tubulointerstitial fibrosis progression through deubiquitinating and stabilizing Snail1 [J]. Eur J Pharmacol, 2023, 947: 175671.
[33]
李变锋, 肖贝贝, 程苗. 血液透析滤过治疗对糖尿病肾病患者肾纤维化的影响[J]. 深圳中西医结合杂志, 2022, 32(12): 83-86.
[34]
Wen Y, Parikh CR. Current concepts and advances in biomarkers of acute kidney injury [J]. Crit Rev Clin Lab Sci,2021, 58(5): 354-368.
[35]
Gutiérrez OM, Shlipak MG, Katz R, et al. Associations of plasma biomarkers of inflammation, fibrosis, and kidney tubular injury with progression of diabetic kidney disease: a cohort study[J]. Am J Kidney Dis, 2022, 79(6): 849-857.
[36]
Malhotra R, Katz R, Jotwani V, et al. Urine markers of kidney tubule cell injury and kidney function decline in SPRINT trial participants with CKD [J]. Clin J Am Soc Nephrol, 2020, 15(3): 349-358.
[37]
Garcia-Fernandez N, Jacobs-Cachá C, Mora-Gutiérrez JM, et al. Matrix metalloproteinases in diabetic kidney disease [J]. J Clin Med, 2020, 9(2): 472.
[38]
Tam FWK, Ong ACM. Renal monocyte chemoattractant protein-1: an emerging universal biomarker and therapeutic target for kidney diseases? [J]. Nephrol Dial Transplant, 2020, 35(2):198-203.
[39]
Grandaliano G, Gesualdo L, Ranieri E, et al. Monocyte chemotactic peptide-1 expression in acute and chronic human nephritides: a pathogenetic role in interstitial monocytes recruitment [J]. J Am Soc Nephrol, 1996, 7(6): 906-913.
[40]
Sarnak MJ, Katz R, Ix JH, et al. Plasma biomarkers as risk factors for incident CKD [J]. Kidney Int Rep, 2022, 7(7):1493-1501.
[41]
Schrauben SJ, Shou H, Zhang X, et al. Association of multiple plasma biomarker concentrations with progression of prevalent diabetic kidney disease: findings from the chronic renal insufficiency cohort (CRIC) study [J]. J Am Soc Nephrol,2021, 32(1): 115-126.
[42]
Bouffette S, Botez I, De Ceuninck F. Targeting galectin-3 in inflammatory and fibrotic diseases [J]. Trends Pharmacol Sci,2023, 44(8): 519-531.
[43]
Wang F, Zhou L, Eliaz A, et al. The potential roles of galectin-3 in AKI and CKD [J]. Front Physiol, 2023, 14: 1090724.
[44]
Sciascia S, Cozzi M, Barinotti A, et al. Renal fibrosis in lupus nephritis [J]. Int J Mol Sci, 2022, 23(22): 14317.
[45]
Cuadrado-Payán E, Ramírez-Bajo MJ, Bañón-Maneus E, et al.Physiopathological role of extracellular vesicles in alloimmunity and kidney transplantation and their use as biomarkers [J].Front Immunol, 2023, 14: 1154650.
[46]
Rayego-Mateos S, Campillo S, Rodrigues-Diez RR, et al.Interplay between extracellular matrix components and cellular and molecular mechanisms in kidney fibrosis [J]. Clin Sci(Lond), 2021, 135(16): 1999-2029.
[47]
刘思梦, 陈思, 周梦, 等. 2021年肾脏病学基础研究进展[J/OL]. 中华肾病研究电子杂志, 2022, 11(2): 79-83.
[48]
吴震宇, 胡亚芬, 董晓芬, 等. 血清CTGF、TGF-β1、MMP2水平对糖尿病肾病肾间质纤维化的预测分析[J/OL]. 中华肾病研究电子杂志, 2022, 11(6): 332-337.
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