Jayachandran Isaivani, Sundararajan Saravanakumar, Paramasivam Prabu, Venkatesan Balachandar, Subramanian Shanthirani C, Balasubramanyam Muthuswamy, Mohan Viswanathan, Manickam Nagaraj
Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention, Gopalapuram, Chennai 600086, India.
Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialties Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention, Gopalapuram, Chennai 600086, India.
Clin Biochem. 2017 Oct;50(15):835-842. doi: 10.1016/j.clinbiochem.2017.05.007. Epub 2017 May 8.
Asymmetric dimethylarginine (ADMA) is involved in the regulation of nitric oxide synthesis and in the maintenance of vascular tone and structure. But the role and status of ADMA in diabetes induced kidney injury is not clear. Hence this study is investigating the role of ADMA in the progression of kidney injury and its circulatory status in Asian Indians with and without diabetic nephropathy.
Recruited study subjects were divided into normal glucose tolerance (NGT), type 2 diabetes mellitus (T2DM) and T2DM with micro or macroalbuminuria. Albuminuria was calculated using urinary albumin and creatinine ratio (UACR). ADMA was measured using ELISA. Kidney cell damage in terms of fibrotic markers and ADMA metabolism in terms of DDAH activity were investigated in kidney fibroblasts and mesangial cells.
There was a significant elevation in plasma ADMA levels in micro and macroalbuminuric diabetic patients. We found a significant positive correlation between ADMA and UACR, serum creatinine, HbA1C and fasting plasma glucose. A cut-off value of ADMA, 0.666μM/l had a sensitivity and specificity of 70.0% and 65.6%, respectively for detecting diabetic nephropathy. DDAH activity was significantly decreased and fibrotic markers such as fibronectin and α-SMA were significantly increased upon high glucose and ADMA treatment.
We are suggesting a causative role of ADMA in the development of kidney injury in terms of renal fibrosis and also a cut point of 0.666μM/l of plasma ADMA level appears to be a predictive risk threshold for diabetic nephropathy in south Asian Indian population.
不对称二甲基精氨酸（ADMA）参与一氧化氮合成的调节以及血管张力和结构的维持。但ADMA在糖尿病所致肾损伤中的作用和状况尚不清楚。因此，本研究旨在调查ADMA在亚洲印度裔糖尿病肾病患者和非糖尿病肾病患者肾损伤进展中的作用及其循环状态。
将招募的研究对象分为正常糖耐量（NGT）组、2型糖尿病（T2DM）组和伴有微量或大量蛋白尿的T2DM组。使用尿白蛋白与肌酐比值（UACR）计算蛋白尿。采用酶联免疫吸附测定法（ELISA）检测ADMA。在肾成纤维细胞和系膜细胞中研究纤维化标志物方面的肾细胞损伤以及二甲基精氨酸二甲胺水解酶（DDAH）活性方面的ADMA代谢。
微量和大量蛋白尿糖尿病患者的血浆ADMA水平显著升高。我们发现ADMA与UACR、血清肌酐、糖化血红蛋白（HbA1C）和空腹血糖之间存在显著正相关。ADMA的截断值为0.666μM/l时，检测糖尿病肾病的敏感性和特异性分别为70.0%和65.6%。高糖和ADMA处理后，DDAH活性显著降低，纤连蛋白和α-平滑肌肌动蛋白（α-SMA）等纤维化标志物显著增加。
我们认为ADMA在肾纤维化导致的肾损伤发展中起因果作用，并且血浆ADMA水平0.666μM/l的切点似乎是南亚印度人群糖尿病肾病的预测风险阈值。
