尿液血管内皮生长因子作为早期糖尿病肾病诊断的生物学标志物

Urinary vascular endothelial growth factor as an early diagnostic biomarker of patients with diabetic nephropathy

目的:评估尿液血管内皮生长因子(uVEGF)能否作为诊断早期糖尿病肾病(DN)生物学标志物。方法:选择2015年4月至10月于郑州大学第一附属医院就诊的2型糖尿病患者94例,分为正常白蛋白尿组(n=30),微量白蛋白尿组(n=33),大量白蛋白尿组(n=31),另选30例健康者作为对照组,用酶联免疫吸附法(ELISA)检测各组uVEGF水平。各组患者病程、血清肌酐、尿酸、空腹血糖、糖化血红蛋白等用Logistic回归分析DN相关临床指标,ROC曲线评估灵敏度及特异性。结果:与健康对照组uVEGF(18.44±0.73 pg/ml)相比,大量白蛋白尿组uVEGF(90.07±7.02 pg/ml,P<0.001),微量白蛋白尿组uVEGF(75.88±9.60 pg/ml,P<0.001)和正常白蛋白尿组uVEGF(33.11±5.20 pg/ml,P=0.02)均显著升高。uVEGF与尿白蛋白(r=0.748,P<0.001)、病程(r=0.714,P<0.001)、血清尿素氮(r=0.466,P=0.004)、估算的肾小球滤过率(r=0.437,P=0.005)、血清肌酐(r=0.412,P=0.013)和总胆固醇(r=0.377,P=0.023)成显著正相关。ROC曲线示:uVEGF早期诊断DN的cut-off值为42.573 pg/ml,敏感度为94.7%,特异度为96.4%。结论:uVEGF可作为早期DN诊断的生物学标志物。

Objective： To evaluate the levels of urinary vascular endothelial growth factor（ VEGF） in type 2diabetic patients with different degrees of diabetic nephropathy（ DN） and to assess the value of vascular endothelial growth factor in the early detection of DN. Methodology： Ninty-four patients with type 2 diabetes were enrolled into this study. They were divided into three groups： normoalbuminuria（ n = 30）, microalbuminuria（ n = 33）, and macroalbuminuria（ n = 31）,according to their urinary albumin excretion,and 30 healthy persons were regarded as normal controls. Urinary VEGF levels were evaluated by enzyme-linked immunosorbent assay. Their clinical and laboratory data were collected. Results： The VEGF levels were significantly increased in macroalbuminuric（ P〈0. 01） 、microalbuminuric（ P〈0. 01） and normoalbuminuric（ P〈0. 01） diabetic patients compared to that control subjects（ P〈0. 05）. Correlation study revealed that VEGF levels were markedly positively correlated to urinary albumin（ r = 0. 748,P〈0. 001）,disease duration（ r = 0. 714,P〈0. 001）,serum urea（ r = 0. 466,P = 0. 004）,eGFR（ r =0. 437,P = 0. 005）,serum creatinine（ r = 0. 412,P = 0. 013）,and Total Cholesterol（ r = 0. 377,P = 0. 023）.Receiver operating characteristic（ ROC） curve analysis of uVEGF levels for early diagnosis and detection of DN revealed that the cut-off value of uVEGF was 42. 6 pg / ml with 94. 7% sensitivity and 96. 4% specificity. Conclusion： The findings of the present study suggest that VEGF may be considered as a novel potential diagnostic biomarker for the early detection of diabetic nephropathy.