Li Zhenzhen, Xu Yuliang, Liu Xianghua, Nie Yali, Zhao Zhanzheng
Institute of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Nephrology, the People's Hospital of Hebi, Hebi, China.
Nephrology (Carlton). 2017 Jan;22(1):58-64. doi: 10.1111/nep.12719.
Our previous study showed that increases of urinary heme oxygenase-1 (uHO-1) could be a potential biomarker indicating evaluating intrarenal oxidative damage in obstructive nephropathy. Activation of oxidative stress is an important mediator of diabetic nephropathy (DN). The aim of this study was to investigate the clinical implications of uHO-1 levels in patients with type 2 diabetes.
Eighty-four type 2 diabetic patients with normoalbuminuria (n=28), microalbuminuria (n=28), and macroalbuminuria (n=28) were included in this study. Control samples were collected from healthy volunteers (n=28) who had normal albuminuria and renal function. Urine HO-1 levels were evaluated by enzyme-linked immunosorbent assay.
Urinary HO-1/creatinine (cr.) levels were significantly elevated in diabetic patients with microalbuminuria and macroalbuminuria compared to those in diabetic patients with normoalbuminuria (P<0.001) and control subjects (all P<0.001). In diabetic patients with normoalbuminuria, uHO-1/cr. levels were also higher than those in controls (P<0.001). Multivariate regression analyses revealed that uHO-1/cr. levels were positively correlated to urinary albumin/creatinine ratio and inversely correlated to glomerular filtration rate. Receiver operating characteristic (ROC) curve analysis of uHO-1/cr. levels for early diagnosis and detection of DN revealed that the cut-off value of uHO-1/cr. was 4.59 ng/mg (sensitivity 75%, specificity 78.6%).
The findings of this study indicate that increases of urine HO-1 levels can be detected in patients with type 2 diabetes before the onset of significant albuminuria, and associated with renal derangement in patients with established diabetic nephropathy. Urinary HO-1 may be used as an early biomarker for diabetic renal injury.
我们之前的研究表明，尿血红素加氧酶-1（uHO-1）水平升高可能是评估梗阻性肾病肾内氧化损伤的潜在生物标志物。氧化应激激活是糖尿病肾病（DN）的重要介导因素。本研究旨在探讨2型糖尿病患者uHO-1水平的临床意义。
本研究纳入了84例2型糖尿病患者，其中正常白蛋白尿患者28例、微量白蛋白尿患者28例、大量白蛋白尿患者28例。对照样本来自白蛋白尿和肾功能正常的健康志愿者（28例）。采用酶联免疫吸附测定法评估尿HO-1水平。
与正常白蛋白尿糖尿病患者（P<0.001）和对照受试者（均P<0.001）相比，微量白蛋白尿和大量白蛋白尿糖尿病患者的尿HO-1/肌酐（cr.）水平显著升高。在正常白蛋白尿糖尿病患者中，uHO-1/cr.水平也高于对照组（P<0.001）。多因素回归分析显示，uHO-1/cr.水平与尿白蛋白/肌酐比值呈正相关，与肾小球滤过率呈负相关。uHO-1/cr.水平用于DN早期诊断和检测的受试者工作特征（ROC）曲线分析显示，uHO-1/cr.的截断值为4.59 ng/mg（敏感性75%，特异性78.6%）。
本研究结果表明，在2型糖尿病患者出现明显白蛋白尿之前即可检测到尿HO-1水平升高，且与已确诊糖尿病肾病患者的肾脏紊乱有关。尿HO-1可作为糖尿病肾损伤的早期生物标志物。
