Satirapoj Bancha, Siritaweesuk Nuttawut, Supasyndh Ouppatham
Division of Nephrology, Department of Medicine , Phramongkutklao Hospital and College of Medicine , Bangkok 10400 , Thailand.
Clin Kidney J. 2014 Aug;7(4):354-60. doi: 10.1093/ckj/sfu059. Epub 2014 Jul 15.
Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mediator of diabetic nephropathy. Urinary angiotensinogen, a novel biomarker of the intrarenal RAAS, is associated with progressive kidney injury. In this study, the authors investigated the determinants of urinary angiotensinogen and its associations with staging of diabetic nephropathy.
Random urine samples were collected from the patients with type 2 diabetes with normoalbuminuria (n = 52), microalbuminuria (n = 52) and macroalbuminuria (n = 51) for the measurement of angiotensinogen by sensitive and specific ELISAs. Control samples were collected from healthy volunteers (n = 20) who had normal albuminuria and renal function.
Urinary angiotensinogen was higher in microalbuminuric and macroalbuminuric diabetes than in controls [63.44 (interquartile range, IQR: 22.08, 174.8) versus 398.38 (IQR: 205.03, 673.68) versus 9.12 (IQR: 3.76, 23.82) ng/mg creatinine, respectively, P < 0.001]. In diabetes with normoalbuminuria, urinary angiotensinogen was also higher than in controls [16.42 (IQR: 7.69, 34.71) versus 9.12 (IQR: 3.76, 23.82) ng/mg creatinine, P = 0.047]. The performance of the biomarker in differentiating each stage of type 2 diabetes from controls was illustrated by receiver-operating characteristic curves. The areas under the curve for the diagnosis of established normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes using urine angiotensinogen (ng/mg creatinine) were 0.62 (95% CI: 0.48-0.77), 0.85 (95% CI: 0.76-0.94) and 0.96 (95% CI: 0.92-1.00), respectively. In addition, the cut-off levels were 9.30 ng/mg (sensitivity 65.4%, specificity 55.0%), 12.32 ng/mg (sensitivity 55.8%, specificity 65.0%) and 17.44 ng/mg (sensitivity 44.2%, specificity 70.0%), respectively, for distinguishing normoalbuminuric type 2 diabetes from healthy controls.
The authors propose that angiotensinogen could be one of the potential urinary biomarkers for diagnosis in established diabetic nephropathy. It appeared even before the significant albuminuria in diabetic nephropathy. It might be useful as an early biomarker of activation of the renin-angiotensin system in diabetic nephropathy.
肾素 - 血管紧张素 - 醛固酮系统（RAAS）的激活是糖尿病肾病的重要介导因素。尿血管紧张素原是肾内RAAS的一种新型生物标志物，与肾脏进行性损伤相关。在本研究中，作者调查了尿血管紧张素原的决定因素及其与糖尿病肾病分期的关联。
收集2型糖尿病患者的随机尿液样本，其中正常白蛋白尿患者（n = 52）、微量白蛋白尿患者（n = 52）和大量白蛋白尿患者（n = 51），通过灵敏且特异的酶联免疫吸附测定法（ELISA）检测血管紧张素原。对照样本取自白蛋白尿和肾功能正常的健康志愿者（n = 20）。
微量白蛋白尿和大量白蛋白尿的糖尿病患者尿血管紧张素原水平高于对照组[分别为63.44（四分位间距，IQR：22.08，174.8）与398.38（IQR：205.03，673.68）与9.12（IQR：3.76，23.82）ng/mg肌酐，P < 0.001]。在正常白蛋白尿的糖尿病患者中，尿血管紧张素原水平也高于对照组[16.42（IQR：7.69，34.71）与9.12（IQR：3.76，23.82）ng/mg肌酐，P = 0.047]。通过受试者操作特征曲线说明了该生物标志物区分2型糖尿病各阶段与对照组的性能。使用尿血管紧张素原（ng/mg肌酐）诊断已确诊的正常白蛋白尿、微量白蛋白尿和大量白蛋白尿2型糖尿病的曲线下面积分别为0.62（95%CI：0.48 - 0.77）、0.85（95%CI：0.76 - 0.94）和0.96（95%CI：0.92 - 1.00）。此外，区分正常白蛋白尿2型糖尿病与健康对照的临界值分别为9.30 ng/mg（敏感性65.4%，特异性55.0%）、12.32 ng/mg（敏感性55.8%，特异性65.0%）和17.44 ng/mg（敏感性44.2%，特异性70.0%）。
作者提出血管紧张素原可能是已确诊糖尿病肾病诊断的潜在尿生物标志物之一。它在糖尿病肾病出现明显白蛋白尿之前就已出现。它可能作为糖尿病肾病中肾素 - 血管紧张素系统激活的早期生物标志物。
