Biochemical Engineering, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune, 411008, India.
Academy of Scientific and Innovative Research, CSIR-NCL Campus, Dr. Homi Bhabha Road, Pune, 411008, India.
Sci Rep. 2020 Feb 19;10(1):2970. doi: 10.1038/s41598-020-59897-1.
Altered circulatory asymmetric and symmetric dimethylarginines have been independently reported in patients with end-stage renal failure suggesting their potential role as mediators and early biomarkers of nephropathy. These alterations can also be reflected in urine. Herein, we aimed to evaluate urinary asymmetric to symmetric dimethylarginine ratio (ASR) for early prediction of diabetic nephropathy (DN). In this cross-sectional study, individuals with impaired glucose tolerance (IGT), newly diagnosed diabetes (NDD), diabetic microalbuminuria (MIC), macroalbuminuria (MAC), and normal glucose tolerance (NGT) were recruited from Dr. Mohans' Diabetes Specialties centre, India. Urinary ASR was measured using a validated high-throughput MALDI-MS/MS method. Significantly lower ASR was observed in MIC (0.909) and MAC (0.741) in comparison to the NGT and NDD groups. On regression models, ASR was associated with MIC [OR: 0.256; 95% CI: 0.158-0.491] and MAC [OR 0.146; 95% CI: 0.071-0.292] controlled for all the available confounding factors. ROC analysis revealed ASR cut-point of 0.95 had C-statistic of 0.691 (95% CI: 0.627-0.755) to discriminate MIC from NDD with 72% sensitivity. Whereas, an ASR cut-point of 0.82 had C-statistic of 0.846 (95% CI: 0.800 - 0.893) had 91% sensitivity for identifying MAC. Our results suggest ASR as a potential early diagnostic biomarker for DN among the Asian Indians.
循环中不对称和对称二甲基精氨酸的改变已在终末期肾衰竭患者中独立报道,提示其作为肾脏病的潜在介质和早期生物标志物的作用。这些改变也可以反映在尿液中。在此,我们旨在评估尿不对称二甲基精氨酸与对称二甲基精氨酸的比值(ASR)在糖尿病肾病(DN)早期预测中的作用。在这项横断面研究中,我们从印度 Mohans 糖尿病专科中心招募了糖耐量受损(IGT)、新诊断糖尿病(NDD)、糖尿病微量白蛋白尿(MIC)、大量白蛋白尿(MAC)和正常糖耐量(NGT)个体。采用经过验证的高通量 MALDI-MS/MS 方法测量尿 ASR。与 NGT 和 NDD 组相比,MIC(0.909)和 MAC(0.741)组的 ASR 显著降低。在回归模型中,ASR 与 MIC [OR:0.256;95%CI:0.158-0.491]和 MAC [OR 0.146;95%CI:0.071-0.292]相关,控制了所有可用的混杂因素。ROC 分析显示,ASR 截断值为 0.95 时,C 统计量为 0.691(95%CI:0.627-0.755),用于区分 MIC 和 NDD 的敏感性为 72%。而 ASR 截断值为 0.82 时,C 统计量为 0.846(95%CI:0.800-0.893),对 MAC 的识别敏感性为 91%。我们的研究结果表明,ASR 可能成为亚洲印度人中 DN 的潜在早期诊断生物标志物。