尿液RBP和ALB在早期糖尿病肾病中的诊断价值及其与外周血MCP-1表达的关系
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摘要
目的分析尿液视黄醇结合蛋白(RBP)、白蛋白(ALB)在早期糖尿病肾病(DN)中的诊断价值及与外周血核细胞趋化蛋白-1(MCP-1)表达的关系。方法选择2015年9月—2017年12月空军军医大学唐都医院肾脏内科收治的2型糖尿病(DM)患者86例作为研究对象,按照患者24 h尿蛋白排泄率的不同分为单纯DM组(46)和早期DN组(40例),另取同期来院检查的健康人42例作为健康对照组,比较3组受试者尿液RBP、ALB水平以及RBP、ALB和RBP+ALB联合诊断阳性率。观察各组外周血MCP-1表达情况,并分析尿液RBP、ALB与血MCP-1的相关性。结果早期DN组、单纯DM组与健康对照组患者的尿液RBP、ALB水平以及外周血MCP-1均逐渐降低,差异均有统计学意义(F/P=40234.35/<0.001、1 975. 16/<0.01、162.46/<0.01)。Ⅰ期、Ⅱ期、Ⅲ期DN患者的尿液RBP、ALB水平以及外周血MCP-1呈现逐渐升高的趋势(F/P=9 177. 06/<0. 001、564. 27/<0. 001、39. 59/<0. 01)。RBP+ALB联合诊断的阳性率为88. 37%,明显高于RBP和ALB单独诊断的阳性率67. 44%,差异具有统计学意义(χ~2/P=10.944/0. 001)。糖尿病肾病患者的尿液RBP和ALB与外周血MCP-1表达均呈正相关(r/P=0. 457/0. 000、0. 483/0. 032)。尿RBP、ALB及RBP+ALB联合诊断早期DN的ROC曲线下面积分别为0. 720、0. 743、0. 982,同时RBP+ALB联合诊断的敏感度以及特异度明显较高。结论尿液RBP+ALB联合诊断早期糖尿病肾病的ROC曲线下面积较大,临床诊断价值较高,并与外周血MCP-1表达呈正相关,可以较为灵敏地反映患者的肾功能损伤。
Objective To investigate the relationship between urinary retinol-binding protein(RBP) and albumin(ALB) in early diabetic nephropathy and its relationship with peripheral blood(nuclear cell chemoattractant protein-1) MCP-1 expression. Methods We selected 86 patients with type 2 diabetes admitted to our hospital from September 2015 to December 2017 as the study subjects, according to the 24-hour urinary protein excretion rate of patients, they were divided into two groups: simple diabetes group(46 cases) and early diabetic nephropathy group(40 cases), and 42 healthy persons from the same period were taken as the control group, the urinary RBP and ALB levels and related diagnostic positivity rates were compared between groups. The expression of MCP-1 in peripheral blood was observed between the groups of patients, and the correlation between urinary RBP, ALB and blood MCP-1 was analyzed. Results The urine RBP, ALB level and peripheral blood MCP-1 in the early diabetic renal group, the simple diabetes group and the control group decreased gradually,the difference was statistically significant( F/P = 40 234. 35/< 0. 001, F/P =1 975. 16/< 0. 001,F/P = 162.46/< 0. 001). The urine RBP, ALB level and peripheral blood MCP-1 of patients with stage I to stage III were gradually increased(F/P = 9 177.06/<0.001, F/P = 564. 27/< 0. 001, F/P = 39. 59/< 0. 001). The positive rate of RBP + ALB combined diagnosis was88.37%,which was significantly higher than the positive rate of RBP and ALB alone diagnosed of 67.44%(χ~2/P=10.944/0.001). The difference was statistically significant. Urinary RBP( r/P = 0. 457/0. 000) and ALB( r/P = 0. 483/0. 032)were positively correlated with peripheral blood MCP-1 expression in patients with diabetic nephropathy. The urinary RBP, ALB and RBP + ALB combined diagnosis of early DN was 0.720, 0.743, and 0.982, respectively. The sensitivity and specificity of RBP + ALB were significantly higher. Conclusion The combined use of urinary RBP + ALB in the diagnosis of early diabetic nephropathy has a larger area under the ROC curve and a higher diagnostic value, it is positively correlated with the expression of MCP-1 in peripheral blood, which can reflect the renal function impairment more sensitive, effectively avoid or delay the occurrence of diabetic nephropathy, and improve the quality of life of patients.
Objective To investigate the relationship between urinary retinol-binding protein(RBP) and albumin(ALB) in early diabetic nephropathy and its relationship with peripheral blood(nuclear cell chemoattractant protein-1) MCP-1 expression. Methods We selected 86 patients with type 2 diabetes admitted to our hospital from September 2015 to December 2017 as the study subjects, according to the 24-hour urinary protein excretion rate of patients, they were divided into two groups: simple diabetes group(46 cases) and early diabetic nephropathy group(40 cases), and 42 healthy persons from the same period were taken as the control group, the urinary RBP and ALB levels and related diagnostic positivity rates were compared between groups. The expression of MCP-1 in peripheral blood was observed between the groups of patients, and the correlation between urinary RBP, ALB and blood MCP-1 was analyzed. Results The urine RBP, ALB level and peripheral blood MCP-1 in the early diabetic renal group, the simple diabetes group and the control group decreased gradually,the difference was statistically significant( F/P = 40 234. 35/< 0. 001, F/P =1 975. 16/< 0. 001,F/P = 162.46/< 0. 001). The urine RBP, ALB level and peripheral blood MCP-1 of patients with stage I to stage III were gradually increased(F/P = 9 177.06/<0.001, F/P = 564. 27/< 0. 001, F/P = 39. 59/< 0. 001). The positive rate of RBP + ALB combined diagnosis was88.37%,which was significantly higher than the positive rate of RBP and ALB alone diagnosed of 67.44%(χ~2/P=10.944/0.001). The difference was statistically significant. Urinary RBP( r/P = 0. 457/0. 000) and ALB( r/P = 0. 483/0. 032)were positively correlated with peripheral blood MCP-1 expression in patients with diabetic nephropathy. The urinary RBP, ALB and RBP + ALB combined diagnosis of early DN was 0.720, 0.743, and 0.982, respectively. The sensitivity and specificity of RBP + ALB were significantly higher. Conclusion The combined use of urinary RBP + ALB in the diagnosis of early diabetic nephropathy has a larger area under the ROC curve and a higher diagnostic value, it is positively correlated with the expression of MCP-1 in peripheral blood, which can reflect the renal function impairment more sensitive, effectively avoid or delay the occurrence of diabetic nephropathy, and improve the quality of life of patients.
引文
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[7]高金芳,张莉,顾红霞,等.血清RBP,Hcy,CysC及尿mALB水平在糖尿病肾病早期诊断中的临床应用[J].现代生物医学进展,2017,17(2):317-319. DOI:10.13241/j. cnki. pmb.2017.02.029.
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[11]徐波,冯云华,张瑛,等.津力达颗粒联合通心络胶囊治疗早期糖尿病肾病患者对微炎性状态及肾功能保护的影响[J].疑难病杂志,2018,17(9):936-939. DOI:10. 3969/j. issn. 1671-6450.2018.09.017.
[12]韦振忠,宋雪霞,廖红霞,等.血液透析加血液灌流对终末期糖尿病肾病患者骨密度以及anti-ox-LDL-Ab水平的影响[J].疑难病杂志,2018, 17(9):900-904. DOI:10. 3969/j. issn. 1671-6450.2018.09.009.
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[15]姜荣艳,唐芙蓉.血清胱抑素C、脂蛋白α、尿微量白蛋白联合检测在糖尿病慢性肾脏疾病早期诊断中的价值[J].疑难病杂志,2017,16(8):788-791. DOI:10. 3969/j. issn. 1671-6450.2017.08.009.
[16]赵元明,李新建,马生聘,等.联合检测尿中NGAL、mAlb、α1-MG在糖尿病肾病中的早期诊断价值[J].中华全科医学,2015,13(10):1678-1680. DOI:10. 16766/j. cnki. issn. 16744152.2015.10.020.
[17] Chacar F,Kogika M,Sanches TR,et al. Urinary Tamm-Horsfall protein, albumin, vitamin D-binding protein,and retinol-binding protein as early biomarkers of chronic kidney disease in dogs[J]. Physiological Reports,2017,5(11):512-523. DOI:10.14814/phy2.13262.
[18]黄赞鸿,张惜铃,陈义杰,等.联合检测Cys-c、Hcy和RBP在糖尿病肾病早期诊断中的意义[J].实用医学杂志,2017,33(2):292-295. DOI:10.3969/j. issn. 1006-5725.2017.02.035.
[19]张岱,叶山东,陈超.尿系列蛋白检测在2型糖尿病肾脏疾病诊断中的意义[J].安徽医学,2017,38(3):339-342.DOI:10.3969/j. issn. 1000-0399. 2017.03.023.
[20]杨丽娟,班安然,陶红.贝前列素钠对糖尿病肾病患者尿白蛋白水平的影响[J].中国医药,2018,13(10):1514-1517. DOI:10.3760/j. issn. 1673-4777.2018.10. 019.
[21]曹玉梅,曹秀娟,黄瑞华,彭丽.黄芪注射液联合阿托伐他汀治疗早期糖尿病肾病的临床效果[J].中国医药,2016,11(4):543-546. DOI:10.3760/cma. j. issn. 1673-4777.2016.04.020.
[22] Moore LB, Sawyer AJ, Charokopos A,et al. Loss of monocyte chemoattractant protein-1 alters macrophage polarization and reduces NFκB activation in the foreign body response[J]. Acta Biomaterialia,2015,11(1):37-47. DOI:10.1016/j. actbio. 2014.09.022.
[2] Ruggenenti P,Cravedi P,Remuzzi G. The RAAS in the pathogenesis and treatment of diabetic nephropathy[J]. Nature Reviews Nephrology,2016,6(6):319-330. DOI:10.1038/nrneph.2010.58.
[3]Maezawa Y,Takemoto M,Yokote K. Cell biology of diabetic nephropathy:Roles of endothelial cells, tubulointerstitial cells and podocytes[J]. Journal of Diabetes Investigation,2015,6(1):3-15. DOI:10.1111/jdi. 12255.
[4] Shahzad K,Bock F,Dong W,et al. NIrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy[J]. Kidney International,2015,87(1):74-84. DOI:10.1038/ki. 2014.271.
[5]Nielsen FS,Ali S,Rossing P,et al. Left ventricular hypertrophy in noninsulin-dependent diabetic patients with and without diabetic nephropathy[J]. Diabetic Medicine A Journal of the British Diabetic Association,2015,14(7):538-546. DOI:10. 1515/cclm-2015-0605.
[6]李春梅,林华棒,梁世周.同型半胱氨酸与性激素结合球蛋白联合检测在糖尿病肾病早期诊断中的意义[J].浙江医学,2016,38(4):295-297. DOI:10.3760/cma. j. issn. 295-297.
[7]高金芳,张莉,顾红霞,等.血清RBP,Hcy,CysC及尿mALB水平在糖尿病肾病早期诊断中的临床应用[J].现代生物医学进展,2017,17(2):317-319. DOI:10.13241/j. cnki. pmb.2017.02.029.
[8] Nagahara K,Dobashi K,Ishikawa T,et al. AICAR attenuates TNFainduced inappropriate secretion of monocyte chemoattractant protein-1 and adiponectin in 3T3-L1 adipocytes[J]. Journal of Atherosclerosis&Thrombosis,2016,23(12):1345-1354. DOI:10. 3892/mmr.2016.1345-1354.
[9]刘阳桦.血清CysC、Hcy、BUN、SCr水平检测对早期糖尿病肾病诊断的价值[J].贵州医药,2016,40(8):863-865.DOI:10.3969/j. issn. 1000-744X.2016.08.034.
[10] Dabhi B,Mistry KN. Oxidative stress and its association with TNF-α-308 G/C and IL-la-889 C/T gene polymorphisms in patients with diabetes and diabetic nephropathy[J]. Gene,2015,562(2):197-202. DOI:10. 1016/j. gene.2015.02.069.
[11]徐波,冯云华,张瑛,等.津力达颗粒联合通心络胶囊治疗早期糖尿病肾病患者对微炎性状态及肾功能保护的影响[J].疑难病杂志,2018,17(9):936-939. DOI:10. 3969/j. issn. 1671-6450.2018.09.017.
[12]韦振忠,宋雪霞,廖红霞,等.血液透析加血液灌流对终末期糖尿病肾病患者骨密度以及anti-ox-LDL-Ab水平的影响[J].疑难病杂志,2018, 17(9):900-904. DOI:10. 3969/j. issn. 1671-6450.2018.09.009.
[13]何建秋,张蕊,卢亚男,等.2型糖尿病肾病患者维生素D与肾素、血管紧张素Ⅱ水平的相关性分析[J].疑难病杂志,2017,16(12):1233-1235. DOI:10. 3969/j. issn. 1671-6450.2017. 12.012.
[14] Shatat IF,Qanungo S,Hudson S,et al. Changes in urine microalbumin-to-creatinine ratio in children with sickle cell disease over time[J]. Frontiers in Pediatrics,2016,7(4):106-113. DOI:10.3389/fped. 2016.00106.
[15]姜荣艳,唐芙蓉.血清胱抑素C、脂蛋白α、尿微量白蛋白联合检测在糖尿病慢性肾脏疾病早期诊断中的价值[J].疑难病杂志,2017,16(8):788-791. DOI:10. 3969/j. issn. 1671-6450.2017.08.009.
[16]赵元明,李新建,马生聘,等.联合检测尿中NGAL、mAlb、α1-MG在糖尿病肾病中的早期诊断价值[J].中华全科医学,2015,13(10):1678-1680. DOI:10. 16766/j. cnki. issn. 16744152.2015.10.020.
[17] Chacar F,Kogika M,Sanches TR,et al. Urinary Tamm-Horsfall protein, albumin, vitamin D-binding protein,and retinol-binding protein as early biomarkers of chronic kidney disease in dogs[J]. Physiological Reports,2017,5(11):512-523. DOI:10.14814/phy2.13262.
[18]黄赞鸿,张惜铃,陈义杰,等.联合检测Cys-c、Hcy和RBP在糖尿病肾病早期诊断中的意义[J].实用医学杂志,2017,33(2):292-295. DOI:10.3969/j. issn. 1006-5725.2017.02.035.
[19]张岱,叶山东,陈超.尿系列蛋白检测在2型糖尿病肾脏疾病诊断中的意义[J].安徽医学,2017,38(3):339-342.DOI:10.3969/j. issn. 1000-0399. 2017.03.023.
[20]杨丽娟,班安然,陶红.贝前列素钠对糖尿病肾病患者尿白蛋白水平的影响[J].中国医药,2018,13(10):1514-1517. DOI:10.3760/j. issn. 1673-4777.2018.10. 019.
[21]曹玉梅,曹秀娟,黄瑞华,彭丽.黄芪注射液联合阿托伐他汀治疗早期糖尿病肾病的临床效果[J].中国医药,2016,11(4):543-546. DOI:10.3760/cma. j. issn. 1673-4777.2016.04.020.
[22] Moore LB, Sawyer AJ, Charokopos A,et al. Loss of monocyte chemoattractant protein-1 alters macrophage polarization and reduces NFκB activation in the foreign body response[J]. Acta Biomaterialia,2015,11(1):37-47. DOI:10.1016/j. actbio. 2014.09.022.