Abstract
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.
Highlights
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
asymmetric to symmetric dimethylarginine ratio (ASR) was significantly lower in MIC (0.909; p < 0.01) and MAC (0.741; p < 0.01) in comparison to the normal glucose tolerance (NGT) and newly diagnosed diabetes (NDD) groups while there were no significant differences between NGT, impaired glucose tolerance (IGT) and NDD groups (Fig. 1)
Waist circumference, systolic and diastolic blood pressure, total cholesterol and serum triglycerides were significantly higher in patients with MIC (p < 0.05) and MAC (p < 0.05) compared to NDD, IGT, and NGT
Summary
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 be reflected in urine. We aimed to evaluate urinary asymmetric to symmetric dimethylarginine ratio (ASR) for early prediction of diabetic nephropathy (DN). There is a lack of data on ASR in relation to nephropathy in this high-risk population This investigation evaluates the efficiency of ASR as a potential marker for early diagnosis of nephropathy in Asian Indians with varying levels of glucose intolerance as well as in patients with T2DM with or without DN
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