[1]孙晨思,李海琦,刘　波.生物标志物在糖尿病肾病早期诊断中的应用研究进展[J].新乡医学院学报,2022,39(2):197-200.[doi:10.7683/xxyxyxb.2022.02.020]
　SUN Chensi,LI Haiqi,LIU Bo.Research progress of biomarkers in early diagnosis of diabetic nephropathy[J].Journal of Xinxiang Medical University,2022,39(2):197-200.[doi:10.7683/xxyxyxb.2022.02.020]
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生物标志物在糖尿病肾病早期诊断中的应用研究进展
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
39
期数:
2022年2
页码:
197-200
栏目:
综述
出版日期:
2022-02-05

文章信息/Info

Title:
Research progress of biomarkers in early diagnosis of diabetic nephropathy
作者:
孙晨思1; 李海琦2; 刘　波1
（1.吉林大学中日联谊医院内分泌代谢科，吉林　长春　130031；2.吉林大学中日联谊医院神经内科，吉林　长春　130031）
Author(s):
SUN Chensi1; LI Haiqi2; LIU Bo1
（1.Department of Endocrinology,China-Japhan Union Hospital of Jilin University,Changchun 130031，Jilin Province,China;2.Department of Neurology,China-Japhan Union Hospital of Jilin University,Changchun 130031,Jilin Province,China)
关键词:
糖尿病肾病; 生物标志物; 晚期糖基化终末产物; 非对称性二甲基精氨酸; 可溶性尿激酶型纤溶酶原激活物受体
Keywords:
diabetic nephropathy; biomarker; advanced glycation end-products; asymmetric dimethylarginine; soluble urokinase-type plasminogen activator receptor
分类号:
R587.2
DOI:
10.7683/xxyxyxb.2022.02.020
文献标志码:
A
摘要:
糖尿病肾病是糖尿病最常见的微血管并发症之一，也是糖尿病患者的重要死亡原因。糖尿病肾病早期临床症状不明显，尿微量白蛋白被广泛认为是糖尿病肾病的早期临床诊断标志物，但有许多患者在肾小球滤过率下降时并未出现蛋白尿，因此，将尿微量白蛋白作为糖尿病肾病早期诊断的敏感生物标志物存在局限性。本文对晚期糖基化终末产物、非对称性二甲基精氨酸、可溶性尿激酶型纤溶酶原激活物受体等新型生物标志物在糖尿病肾病早期诊断中的应用研究进展进行综述，以期为糖尿病肾病的早期诊断和治疗提供新的靶点。
Abstract:
Diabetic nephropathy is one of the most common microvascular complications of diabetes mellitus，it is also an important cause of death in diabetic patients.In the early stage of diabetic nephropathy，the clinical symptoms are not obvious.Urinary microalbumin has been widely regarded as an early clinical diagnostic marker of diabetic nephropathy,however,many patients didn′t have proteinuria when the glomerular filtration rate decreased.Therefore urinary microalbumin as a sensitive biomarker for early detection for diabetic nephropathy is limited.This article reviews the research progress of appicication of some new biomarkers in early diagnosis of diabetic nephropathy，including advanced glycation end-products，asymmetric dimethylarginine，soluble urokinase-type plasminogen activator receptor,in order to provide new targets for early diagnosis and treatment of diabetic nephropathy.

参考文献/References:

［1］　ZIMMET P Z.Diabetes and its drivers:the largest epidemic in human history［J］.Clin Diabetes Endocrinol,2017,3:1.
［2］　SAEEDI P,PETERSOHN I,SALPEA P,et al.Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045:results from the International Diabetes Federation Diabetes Atlas,9th edition［J］.Diabetes Res Clin Pract,2019,157:107843.
［3］　QUAN K Y,YAP C G,JAHAN N K,et al.Review of early circulating biomolecules associated with diabetes nephropathy-ideal candidates for early biomarker array test for DN［J］.Diabetes Res Clin Pract,2021,182:109122.
［4］　BARUTTA F,BERNARDI S,GARGIULO G,et al.SGLT2 inhibition to address the unmet needs in diabetic nephropathy［J］.Diabetes Metab Res Rev,2019,35(7):e3171.
［5］　KICONCO R,RUGERA S P,KIWANUKA G N.Microalbuminuria and traditional serum biomarkers of nephropathy among diabetic patients at mbarararegional referral hospital in south Western Uganda［J］.J Diabetes Res,2019,2019:3534260.
［6］　THIPSAWAT S.Early detection of diabetic nephropathy in patient with type 2 diabetes mellitus:a review of the literature［J］.Diab Vasc Dis Res,2021,18(6):14791641211058856.
［7］　TRAMONTI G,KANWAR Y S.Tubular biomarkers to assess progression of diabetic nephropathy［J］.Kidney Int,2011,79(10):1042-1044.
［8］　WASUNG M E,CHAWLA L S,MADERO M.Biomarkers of renal function,which and when［J］.Clin Chim Acta,2015,438:350-357.
［9］　MOK C C.Biomarkers for lupus nephritis:a critical appraisal［J］.J Biomed Biotechnol,2010,2010:638413.
［10］　ZABAD I E M,AMIN M N,EL-SHISHTAWY M M.Protective effect of vanillin on diabetic nephropathy by decreasing advanced glycation end products in rats［J］.Life Sci,2019,239:117088.
［11］　丁珊珊,刘星玥,马浩.晚期糖基化终末产物介导糖尿病慢性并发症的分子机制研究进展［J］.江苏医药,2020,46(2):202-206.
DING S S,LIU X Y,MA H.Advances in molecular mechanisms of advanced glycation end products mediating diabetic chronic complications［J］.Jiangsu Med J,2020,46(2):202-206.
［12］　VELICHKOVA S,FOUBERT K,PIETERS L.Naturalproducts as a source of inspiration for novel inhibitors of advanced glycation endproducts (AGEs) formation［J］.Planta Med,2021,87(10-11):780-801.
［13］　TANG D,HE W J,ZHANG Z T,et al.Protective effects of Huang-Lian-Jie-Du decoction on diabetic nephropathy through regulating AGEs/RAGE/Akt/Nrf2 pathway and metabolic profiling in db/db mice［J］.Phytomedicine,2022,95:153777.
［14］　WU X Q,ZHANG D D,WANG Y N,et al.AGE/RAGE in diabetic kidney disease and ageing kidney［J］.Free Radic Biol Med,2021,171:260-271.
［15］　LIAN Y,ZHU M,CHEN J,et al.Characterization of a novel polysaccharide from Moutan Cortex and its ameliorative effect on AGEs-induced diabetic nephropathy［J］.Int J Biol Macromol,2021,176:589-600.
［16］　RUNGRATANAWANICH W,QU Y,WANG X,et al.Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury［J］.Exp Mol Med,2021,53(2):168-188.
［17］　YANG P Y,LI P C,FENG B.Protective effects of gliclazide on high glucose and AGEs-induced damage of glomerular mesangial cells and renal tubular epithelial cells via inhibiting RAGE-p22phox-NF-kB pathway［J］.Eur Rev Med Pharmacol Sci,2019,23(20):9099-9107.
［18］　JEONG S R,LEE K W.Methylglyoxal-derived advanced glycation end product (AGE4)-induced apoptosis leads to mitochondrial dysfunction and endoplasmic reticulum stress through the RAGE/JNK pathway in kidney cells［J］.Int J Mol Sci,2021,22(12):6530.
［19］　BEISSWENGER P J,HOWELL S K,RUSSELL G B,et al.Early progression of diabetic nephropathy correlates with methylglyoxal-derived advanced glycation end products［J］.Diabetes Care,2013,36(10):3234-3239.
［20］　TSIKASD.Urinarydimethylamine (DMA) and its precursor asymmetric dimethylarginine (ADMA) in clinical medicine,in the context of nitric oxide (NO) and beyond［J］.J Clin Med,2020,9(6):1843.
［21］　HSU C N,TAIN Y L.Asymmetricdimethylarginine (ADMA) in pediatric renal diseases:frompathophysiological phenomenon to clinical biomarker and beyond［J］.Children(Basel),2021,8(10):837.
［22］　OLIVA-DAMASO E,OLIVA-DAMASO N,RODRIGUEZ-ESPARRAGON F,et al.Asymmetric(ADMA) and symmetric (SDMA) dimethylarginines in chronic kidney disease:aclinical approach［J］.Int J Mol Sci,2019,20(15):3668.
［23］　DOWSETT L,HIGGINS E,ALANAZI S,et al.ADMA:akey player in the relationship between vascular dysfunction and inflammation in atherosclerosis［J］.J Clin Med,2020,9(9):3026.
［24］　CHEN C H,ZHAO J F,HSU C P,et al.The detrimental effect of asymmetric dimethylarginine on cholesterol efflux of macrophage foam cells:role of the NOX/ROS signaling［J］.Free Radic Biol Med,2019,143:354-365.
［25］　WANG D,LI H,WEIR E K,et al.Dimethylarginine dimethylaminohydrolase 1 deficiency aggravates monocrotaline-induced pulmonary oxidative stress,pulmonary arterial hypertension and right heart failure in rats［J］.Int J Cardiol,2019,295:14-20.
［26］　马雪丰,张景耀,毛庆,等.蛋白质精氨酸甲基转移酶1-非对称性二甲基精氨酸-二甲基精氨酸二甲胺水解酶1路径在肝纤维化、肾小管间质纤维化大鼠组织中的作用及意义［J］.中国全科医学,2017,20(12):1474-1479.
MA X F,ZHANG J Y,MAO Q,et al.Role and significance of PRMT1-ADMA-DDAH1 pathway in rats with hepatic and renal tubulointerstitial fibrosis［J］.Chin Gen Pract,2017,20(12):1474-1479.
［27］　HOTTA Y,KATAOKA T,KIMURA K.Testosterone deficiency and endothelial dysfunction:nitric oxide,asymmetric dimethylarginine,and endothelial progenitor cells［J］.Sex Med Rev,2019,7(4):661-668.
［28］　ZHAO W C,LI G,HUANG C Y,et al.Asymmetric dimethylarginine:an crucial regulator in tissue fibrosis［J］.Eur J Pharmacol,2019,854:54-61.
［29］　JAYACHANDRAN I,SUNDARARAJAN S,PARAMASIVAM P,et al.Association of circulatory asymmetric dimethylarginine (ADMA) with diabetic nephropathy in Asian Indians and its causative role in renal cell injury［J］.Clin Biochem,2017,50(15):835-842.
［30］　SHI L L,ZHAO C Y,WANG H Y,et al.Dimethylarginine dimethylaminohydrolase 1 deficiency induces the epithelial to mesenchymal transition in renal proximal tubular epithelial cells and exacerbates kidney damage in aged and diabetic mice［J］.Antioxid Redox Sign,2017,27(16):1347-1360.
［31］　GROENEVELD O N,VAN DEN BERG E,JOHANSEN O E,et al.Oxidative stress and endothelial dysfunction are associated with reduced cognition in type 2 diabetes［J］.Diab Vasc Dis Res,2019,16(6):577-581.
［32］　QUOC HOANG T A,TAM V,THANG H V.Plasma asymmetric dimethylarginine and its association with some of cardiovascular disease risk factors in chronic kidney disease［J］.Med J Malaysia,2019,74(3):209-214.
［33］　MANGONI A A,TOMMASI S,SOTGIA S,et al.Asymmetricdimethylarginine:a key player in the pathophysiology of endothelial dysfunction,vascular inflammation and atherosclerosis in rheumatoid arthritis［J］.Curr Pharm Des,2021,27(18):2131-2140.
［34］　WANG L,ZHANG D,ZHENG J,et al.Actin cytoskeleton-dependent pathways for ADMA-induced NF-kappaB activation and TGF-beta high expression in human renal glomerular endothelial cells［J］.Acta BiochimBiophys Sin (Shanghai),2012,44(11):918-923.
［35］　SHARMA M,ZHOU Z,MIURA H,et al.ADMA injures the glomerular filtration barrier:role of nitric oxide and superoxide［J］.Am J Physiol Renal Physiol,2009,296(6):F1386-1395.
［36］　KRZYZANOWSKA K,MITTERMAYER F,SHNAWA N,et al.Asymmetrical dimethylarginine is related to renal function,chronic inflammation and macroangiopathy in patients with type 2 diabetes and albuminuria［J］.Diabetic Med,2007,24(1):81-86.
［37］　HANAI K,BABAZONO T,NYUMURA I,et al.Asymmetric dimethylarginine is closely associated with the development and progression of nephropathy in patients with type 2 diabetes［J］.Nephrol Dial Transpl,2009,24(6):1884-1888.
［38］　WEI C,SPEAR R,HAHM E,et al.suPAR,acirculating kidney disease factor［J］.Front Med (Lausanne),2021,8:745838.
［39］　LUPU ORU G,AILINC AˇI I,SOROHAN B M,et al.Serum soluble urokinase plasminogen activator receptor as a potential biomarker of renal impairment severity in diabetic nephropathy［J］.Diabetes Res Clin Pract,2021,182:109116.
［40］　HUANG Q,XIONG H,YAN P,et al.The diagnostic and prognostic value of suPAR in patients with sepsis:a systematic review and meta-analysis［J］.Shock,2020,53(4):416-425.
［41］　ZDIRIK B,STUEVEN A,KNORR J,et al.Soluble urokinase plasminogen activator receptor (suPAR) concentrations are elevated in patients with neuroendocrine malignancies［J］.J Clin Med,2020,9(6):1647.
［42］　ENOCSSON H,LUKIC T,ZIEGELASCH M,et al.Serum levels of the soluble urokinase plasminogen activator receptor (suPAR) correlates with disease activity in early rheumatoid arthritis and reflects joint damage over time［J］.Transl Res,2021,232:142-149.
［43］　ISOLA G,POLIZZI A,ALIBRANDI A,et al.Independent impact of periodontitis and cardiovascular disease on elevated soluble urokinase-type plasminogen activator receptor (suPAR) levels［J］.J Periodontol,2021,92(6):896-906.
［44］　GUTHOFF M,WAGNER R,RANDRIANARISOA E,et al.Soluble urokinase receptor (suPAR) predicts microalbuminuria in patients at risk for type 2 diabetes mellitus［J］.Sci Rep,2017,7:40627.
［45］　WU C Z,CHANG L C,LIN Y F,et al.Urokinase plasminogen activator receptor and its soluble form in common biopsy-proven kidney diseases and in staging of diabetic nephropathy［J］.Clin Biochem,2015,48(18):1324-1329.
［46］　KIM E Y,DRYER S E.RAGE and αVB3-integrin are essential for suPAR signaling in podocytes［J］.Biochim Biophys Acta Mol Basis Dis,2021,1867(10):166186.

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更新日期/Last Update: 2022-02-05