El-Dawla Nada M Qamar, Sallam Al-Aliaa M, El-Hefnawy Mohamed H, El-Mesallamy Hala O
Biochemistry Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt.
Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Abassia, Cairo, 11566, Egypt.
Clin Exp Nephrol. 2019 Aug;23(8):1050-1057. doi: 10.1007/s10157-019-01744-3. Epub 2019 May 18.
Diabetic nephropathy (DN) is a severe complication of diabetes mellitus (DM). Many mechanisms are involved in its development; one of these mechanisms is epithelial-to-mesenchymal transition (EMT). During EMT, losing of the epithelial biomarkers like E-cadherin and increasing of mesenchymal biomarkers like periostin are very characteristic.
The study included 19 healthy controls and 71 DN patients categorized according to their urinary albumin-to-creatinine ratio (UACR) into 19 normoalbuminuric (UACR < 30 mg/g), 37 microalbuminuric (UACR 30-300 mg/g), and 15 macroalbuminuric (UACR > 300 mg/g) patients. Fasting plasma glucose (FPG), glycated hemoglobin (HbA%), serum creatinine (Cr), and urea were measured. E-cadherin and periostin were measured by ELISA and compared among groups.
Concerning E-cadherin levels, in comparison to control group, there were significantly decreased in all groups (0.94, 0.52, and 0.14 ng/mL in normoalbuminuria, microalbuminuria, and macroalbuminuria groups; respectively). For periostin levels, nonsignificant increase in normoalbuminuria (0.32 ng/mL) than control group (0.3 ng/mL) was observed. There was a significant increase in other groups with the highest values in macroalbuminuria group (1.66 ng/mL). E-cadherin and periostin were correlated with each other (r = - 0.353, P < 0.001). UACR was negatively correlated with E-cadherin and positively correlated with periostin. ROC curve analyses showed that the AUC to diagnose established microalbuminuria using E-cadherin was 0.998 (95% CI 0. 932-1), and using periostin was 0.833 (95% CI 0.709-0.919).
Serum E-cadherin and periostin could be considered as reliable biomarkers involved in DN pathogenesis and linked to its stages.
糖尿病肾病(DN)是糖尿病(DM)的一种严重并发症。其发病涉及多种机制;其中一种机制是上皮-间质转化(EMT)。在EMT过程中,上皮生物标志物如E-钙黏蛋白的丢失和间质生物标志物如骨膜蛋白的增加非常具有特征性。
该研究纳入了19名健康对照者和71名DN患者,根据尿白蛋白与肌酐比值(UACR)将患者分为19名正常白蛋白尿患者(UACR<30mg/g)、37名微量白蛋白尿患者(UACR 30 - 300mg/g)和15名大量白蛋白尿患者(UACR>300mg/g)。检测空腹血糖(FPG)、糖化血红蛋白(HbA%)、血清肌酐(Cr)和尿素。通过酶联免疫吸附测定(ELISA)法检测E-钙黏蛋白和骨膜蛋白,并在各组之间进行比较。
关于E-钙黏蛋白水平,与对照组相比,所有组均显著降低(正常白蛋白尿组、微量白蛋白尿组和大量白蛋白尿组分别为0.94、0.52和0.14ng/mL)。对于骨膜蛋白水平,观察到正常白蛋白尿组(0.32ng/mL)较对照组(0.3ng/mL)无显著升高。其他组有显著升高,大量白蛋白尿组最高(1.66ng/mL)。E-钙黏蛋白和骨膜蛋白相互相关(r = -0.353,P<0.001)。UACR与E-钙黏蛋白呈负相关,与骨膜蛋白呈正相关。ROC曲线分析表明,使用E-钙黏蛋白诊断已确诊微量白蛋白尿的曲线下面积(AUC)为0.998(95%置信区间0.932 - 1),使用骨膜蛋白诊断的AUC为0.833(95%置信区间0.709 - 0.919)。
血清E-钙黏蛋白和骨膜蛋白可被视为参与DN发病机制并与其分期相关的可靠生物标志物。