触珠蛋白对早期糖尿病肾病患者肾功能损害的预测作用

doi:10.3969/j.issn.1006-7795.2019.01.010

首都医科大学学报 ›› 2019, Vol. 40 ›› Issue (1): 53-58.doi: 10.3969/j.issn.1006-7795.2019.01.010

• 糖尿病研究从基础到临床 • 上一篇下一篇

触珠蛋白对早期糖尿病肾病患者肾功能损害的预测作用

郑晓敏^1,2,3,4, 杨芳远^2,3,4, 刘翠平¹, 杨金奎^2,3,4

1. 清华大学附属垂杨柳医院内分泌科, 北京 100022;
2. 首都医科大学附属北京同仁医院内分泌科, 北京 100730;
3. 糖尿病防治研究北京市重点实验室, 北京 100730;
4. 北京市糖尿病研究所, 北京 100730

收稿日期:2018-11-08 出版日期:2019-01-21 发布日期:2019-01-23
通讯作者: 杨金奎 E-mail:jinkui.yang@gmail.com
基金资助:
国家重点研发项目（2017YFC0909600），国家自然科学基金（81561128015），北京市科委科技计划项目（D171100002817005）。

Predictive value of haptoglobin on renal dysfunction in patients with early diabetic kidney disease

Zheng Xiaomin^1,2,3,4, Yang Fangyuan^2,3,4, Liu Cuiping¹, Yang Jinkui^2,3,4

1. Department of Endocrinology, Chuiyangliu Hospital, Tsinghua University, Beijing 100022, China;
2. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China;
3. Beijing Key Laboratory of Diabetes Research and Care, Beijing 100730, China;
4. Beijing Diabetes Institute, Beijing 100730, China

Received:2018-11-08 Online:2019-01-21 Published:2019-01-23
Supported by:
This study was supported by National Key Research and Development Program of China (2017YFC0909600), National Natural Science Foundation of China(81561128015), Scientific Project of Beijing Municipal Science & Technology Commission (D171100002817005).

摘要/Abstract

摘要： 糖尿病肾脏疾病（diabetic kidney disease，DKD）是糖尿病的重要合并症，是造成终末期肾病的重要原因，寻找早期预测肾功能损害的生物标志物具有重要临床意义。目前临床使用的DKD诊断的指标主要是尿白蛋白、肌酐、尿素氮等，但由于其特异度和灵敏度尚不理想，还需要进一步寻找DKD的早期诊断指标。多个研究表明尿触珠蛋白（haptoglobin，Hp）在早期DKD中可预测肾功能的进展，本文就Hp对早期糖尿病肾病患者肾功能损害的预测作用及相关机制进行综述。

关键词: 触珠蛋白, 糖尿病肾脏疾病, 预测

Abstract: Diabetic kidney disease is an important complication that occurs in some diabetes patients, and it is a leading cause of end-stage renal disease.Biomarkers predicting the deterioration of renal function are important in clinical settings.Microalbuminuria, creatinine and urea nitrogen are widely used as markers to predict renal function decline, but the predictive value of these markers for kidney damage are limited.It is necessary to further search the indicators of diabetic kidney disease for early diagnosis. Several studies suggested that urine haptoglobin is a novel biomarker for predicting kidney damage in patients with diabetes.This article reviews the clinical significance and related mechanisms of the predictive value of haptoglobin on renal dysfunction in patients with early diabetic kidney disease.

Key words: haptoglobin, diabetic kidney disease, predict

中图分类号:

R692
R58

郑晓敏, 杨芳远, 刘翠平, 杨金奎. 触珠蛋白对早期糖尿病肾病患者肾功能损害的预测作用[J]. 首都医科大学学报, 2019, 40(1): 53-58.

Zheng Xiaomin, Yang Fangyuan, Liu Cuiping, Yang Jinkui. Predictive value of haptoglobin on renal dysfunction in patients with early diabetic kidney disease[J]. Journal of Capital Medical University, 2019, 40(1): 53-58.

参考文献

[1] Wang L, Gao P, Zhang M, et al. Prevalence and ethnic pattern of diabetes and prediabetes in China in 2013[J].JAMA, 2017, 317(24):2515-2523.
[2] American Diabetes Association. Microvascular complications and foot care:standards of medical care in diabetes-2018[J]. Diabetes Care, 2018,41(Suppl 1):S105-S118.
[3] Zhang L, Long J, Jiang W, et al.Trends in chronic kidney disease in China[J]. N Engl J Med, 2016, 375(9):905-906.
[4] KDOQI.KDOQI clinical practice guidelines and clinical practice recommendations for diabetes and chronic kidney disease[J].Am J Kidney Dis, 2007,49(2 Suppl 2):S12-154.
[5] American Diabetes Association. Standards of medical care in diabetes-2013[J]. Diabetes Care, 2013,36 Suppl 1:S11-66.
[6] Argyropoulos C P, Chen S S, Ng Y H, et al.Rediscovering beta-2 microglobulin as a biomarker across the spectrum of kidney diseases[J]. Front Med (Lausanne), 2017, 4:73.
[7] Monteiro M B, Thieme K, Santos-Bezerra D P, et al. Beta-2-microglobulin (B2M) expression in the urinary sediment correlates with clinical markers of kidney disease in patients with type 1 diabetes[J]. Metabolism, 2016,65(6):816-824.
[8] Zhou B, Zou H, Xu G. Clinical utility of serum cystatin C in predicting diabetic nephropathy among patients with diabetes mellitus:a meta-analysis[J]. Kidney Blood Press Res, 2016,41(6):919-928.
[9] Gluhovschi C, Gluhovschi G, Petrica L, et al. Urinary biomarkers in the assessment of early diabetic nephropathy[J]. J Diabetes Res, 2016,2016:4626125.
[10] Yang J K, Wang Y Y, Liu C, et,al. Urine proteome specific for eye damage can predict kidney damage in patients with type 2 diabetes:a case-control and a 5.3-year prospective cohort study[J].Diabetes Care, 2017,40(2):253-260.
[11] Bhensdadia N M, Hunt K J, Lopes-Virella M F, et al. Urine haptoglobin levels predict early renal functional decline in patients with type 2 diabetes[J]. Kidney Int, 2013,83(6):1136-1143.
[12] Liu J J, Liu S, Wong M D, et al.Urinary haptoglobin predicts rapid renal function decline in asians with type 2 diabetes and early kidney disease[J]. J Clin Endocrinol Metab, 2016,101(10):3794-3802.
[13] Raugei G, Bensi G, Colantuoni V, et al. Sequence of human haptoglobin cDNA:evidence that the alpha and beta subunits are coded by the same mRNA[J]. Nucleic Acids Res, 1983,11(17):5811-5819.
[14] Bowman B H, Kurosky A. Haptoglobin:the evolutionary product of duplication, unequal crossing over, and point mutation[J]. Adv Hum Genet, 1982,12:189-261, 453-454.
[15] Zhao K W, Brochmann Murray E J, Murray S S. HK2 proximal tubule epithelial cells synthesize and secrete plasma proteins predominantly through the apical surface[J]. J Cell Biochem, 2017,118(4):924-933.
[16] Maffei M, Barone I, Scabia G, et al.The multifaceted Haptoglobin in the context of adipose tissue and metabolism[J]. Endocr Rev, 2016,37(4):403-416.
[17] Schaer D J, Vinchi F, Ingoglia G, et al.Haptoglobin, hemopexin, and related defense pathways-basic science, clinical perspectives, and drug development[J]. Front Physiol, 2014,5:415.
[18] Yang H, Wang H, Levine Y A, et al. Identification of CD163 as an antiinflammatory receptor for HMGB1-haptoglobin complexes[J]. JCI Insight, 2016,1(7):e85375.
[19] Etzerodt A, Moestrup S K. CD163 and inflammation:biological, diagnostic, and therapeutic aspects[J]. Antioxid Redox Signal,2013,18(17):2352-2363.
[20] Reeder B J. The redox activity of hemoglobins:from physiologic functions to pathologic mechanisms[J]. Antioxid Redox Signal,2010,13(7):1087-1123.
[21] Deuel J W, Schaer C A, Boretti F S, et al.Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response[J]. Cell Death Dis, 2016,7:e2064.
[22] Chintagari N R, Nguyen J, Belcher J D, et al. Haptoglobin attenuateshemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease[J]. Blood Cells Mol Dis, 2015,54(3):302-306.
[23] Arredouani M S, Kasran A, Vanoirbeek J A, et al. Haptoglobin dampens endotoxin-induced inflammatory effects both in vitro and in vivo[J]. Immunology, 2005, 114(2):263-271.
[24] Ghuman S, Van Hemelrijck M, Garmo H,et al.Serum inflammatory markers and colorectal cancer risk and survival[J].Br J Cancer. 2017,116(10):1358-1365.
[25] Vanuytsel T, Vermeire S, Cleynen I. The role of haptoglobin and its related protein, zonulin, in inflammatory bowel disease[J].Tissue Barriers,2013,1(5):e27321.
[26] Shen H, Heuzey E, Mori D N, et al. Haptoglobin enhances cardiac transplant rejection[J]. Circ Res, 2015,116(10):1670-1679.
[27] Dalan R, Liu X, Goh L L. Endothelial cell apoptosis correlates with low haptoglobin concentrations in diabetes[J].DiabVasc Dis Res, 2017,14(6):534-539.
[28] Aggarwal A, Gupta R, Negi V S, et al. Urinary haptoglobin, alpha-1 anti-chymotrypsin and retinol binding protein identified by proteomics as potential biomarkers for lupus nephritis[J]. Clin Exp Immunol, 2017,188(2):254-262.
[29] Zager R A, Vijayan A, Johnson A C. Proximal tubule haptoglobin gene activation is an integral component of the acute kidney injury "stress response"[J]. Am J Physiol Renal Physiol, 2012,303(1):F139-148.
[30] Gburek J, Verroust P J, Willnow T E, et al.Megalin and cubilin are endocytic receptors involved in renal clearance of hemoglobin[J]. J Am SocNephrol, 2002,13(2):423-430.
[31] Asleh R, Guetta J, Kalet-Litman S,et al. Haptoglobin genotype-and diabetes-dependent differences in iron-mediated oxidative stress in vitro and in vivo[J] Circ Res, 2005,96(4):435-441.
[32] Asleh R, Nakhoul F M, Miller-Lotan R, et al. Poor lysosomal membrane integrity in proximal tubule cells of haptoglobin 2-2 genotype mice with diabetes mellitus[J]. Free Radic Biol Med, 2012,53(4):779-786.
[33] Nankivell B J, Tay Y C, Boadle R A, et al. Lysosomal iron accumulation in diabetic nephropathy[J]. Ren Fail, 1994,16(3):367-381.
[34] Tagawa A, Yasuda M, Kume S, et al. Impaired podocyte autophagy exacerbates proteinuria in diabetic nephropathy[J]. Diabetes, 2016,65(3):755-767.
[35] Amanzadeh M, Mota A, Zarghami N, et al. Association between matrix metalloproteinase-3 activity and glomerular filtration rate and albuminuria status in patients with type 2 diabetes mellitus[J]. Iran J Kidney Dis, 2018,12(1):40-47.
[36] Conway B, Fried L, Orchard T. Hemoglobin and overt nephropathy complications in type 1 diabetes[J]. Ann Epidemiol, 2008,18(2):147-155.
[37] Dessapt-Baradez C, Woolf A S, White K E, et al. Targeted glomerular angiopoietin-1 therapy for early diabetic kidney disease[J]. J Am Soc Nephrol, 2014,25(1):33-42.
[38] Park S J, Sang H B, Oh M K, et al. Enhancement of angiogenic and vasculogenic potential of endothelial progenitor cells by haptoglobin[J]. FEBS Lett, 2009, 583(19):3235-3240.
[39] Smeets M B, Pasterkamp G, Lim S K, et al. Nitric oxide synthesis is involved in arterial haptoglobin expression after sustained flow changes[J]. FEBS Lett, 2002, 529(2):221-224.
[40] Brosius F C, Pennathur S. How to find a prognostic biomarker for progressive diabetic nephropathy[J]. Kidney Int, 2013,83(6):996-998.
[41] Macisaac R J, Ekinci E I, Jerums G. Markers of and risk factors for the development and progression of diabetic kidney disease[J]. Am J Kidney Dis, 2014, 63(2 Suppl 2):S39-62.

触珠蛋白对早期糖尿病肾病患者肾功能损害的预测作用

Predictive value of haptoglobin on renal dysfunction in patients with early diabetic kidney disease

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	冯颖, 时克, 王宪波. 肝硬化合并肠系膜上静脉栓塞患者2年预后预测模型的构建与验证[J]. 首都医科大学学报, 2023, 44(1): 107-114.
[2]	王梦迪, 郭弋凡, 庞彦余, 刘羽飞, 赵文景. 保肾通络方含药血清调节线粒体自噬对高糖诱导下足细胞氧化损伤的影响[J]. 首都医科大学学报, 2022, 43(5): 687-693.
[3]	邬金鸣, 孙海霞, 王嘉阳, 钱庆. 基于电子病历的重症老年患者急性肾损伤连续风险预测研究[J]. 首都医科大学学报, 2022, 43(4): 600-609.
[4]	杨丰春, 郑思, 李姣. 可解释机器学习方法在疾病预测中的应用:脓毒血症患者死亡风险研究[J]. 首都医科大学学报, 2022, 43(4): 610-617.
[5]	彭荣荣, 刘芸男, 杨小丽, 杨冬燕. 基于时间序列分析的单采血小板临床需求预测模型研究[J]. 首都医科大学学报, 2020, 41(2): 231-236.
[6]	郑晓敏, 杨芳远, 刘翠平, 杨金奎. 储存条件对尿触珠蛋白检测的影响[J]. 首都医科大学学报, 2020, 41(1): 21-26.
[7]	冷菲, 李巍. 基于XGBoost对肺鳞癌和肺腺癌的分类预测[J]. 首都医科大学学报, 2019, 40(6): 889-893.
[8]	徐文剑, 李巍. 基于全血基因表达谱的脑组织基因表达量预测模型的建立[J]. 首都医科大学学报, 2019, 40(5): 731-737.
[9]	郝鹏, 冯斯婷, 甄雷, 王晓, 王春梅, 聂绍平. SYNTAX II评分对急性ST段抬高型心肌梗死患者直接PCI术后无复流的预测价值[J]. 首都医科大学学报, 2019, 40(5): 744-748.
[10]	宋丽妮, 刘敬怡, 张怡尘, 曹曦, 袁明霞, 杨金奎. 糖尿病肾病早期诊断标志物的研究新进展[J]. 首都医科大学学报, 2017, 38(2): 145-150.
[11]	孙胜军, 韩丽萍, 苏亚萍, 高培毅. “动态点征”在CTP原始图像上对急性脑出血增长的预测价值[J]. 首都医科大学学报, 2017, 38(1): 72-77.
[12]	李春芝, 赵鑫, 郭士强. 血浆NT-proBNP和总胆固醇浓度联合预测心脏瓣膜病病人恶性心律失常的价值[J]. 首都医科大学学报, 2017, 38(1): 108-112.
[13]	朱虹, 贾竑晓, 阎爱国, 职利花. 齐拉西酮治疗精神分裂症疗效及不良反应的相关因素分析[J]. 首都医科大学学报, 2016, 37(2): 164-167.
[14]	曹凯, 王友信, 刘相佟, 陶丽新, 郭晋, 宋曼殳, 于鑫玮, 杨金奎, 王嵬, 郭秀花, 杨光燃, 魏文斌. 血浆糖基与代谢综合征血糖组分关联性研究[J]. 首都医科大学学报, 2015, 36(4): 614-617.
[15]	武红琴, 阮祥燕, 卢永军, 田玄玄, 张颖, 崔亚美, 赵越, 杜娟, 李扬璐, Diethelm Wallwiener, Alfred O. Mueck. 多囊卵巢综合征患者合并代谢综合征的患病率和预测指标[J]. 首都医科大学学报, 2015, 36(4): 553-558.