Diabetic Nephropathy (DN) is among the most significant long-term complications associated with type 2 diabetes mellitus (T2DM). The risk of End-Stage Renal Disease (ESRD) and resulting premature morbidity and mortality is estimated to increase 12-fold with diabetes.
Microalbuminuria (MIC) is an early non-invasive marker of renal disease and its progression. However, it takes several years of diabetes for MIC to occur. Interventions are also much less effective in some patients with MIC, who manifest advanced pathological changes. Development of sensitive early-stage disease markers and alternative diagnostic approaches are thus essential for the detection of DN.
A recent study has identified urinary Asymmetric to Symmetric Dimethylarginine Ratio (ASR) as a potential biomarker for early prediction of DN, even in those newly diagnosed with diabetes. The research, published in the peer-reviewed journal Scientific Reports on February 19, is a multidisciplinary collaborative effort of scientists from the National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, the Council of Scientific and Industrial Research (CSIR) – National Chemical Laboratory (CSIR-NCL), Pune, and Madras Diabetes Research Foundation (MDRF), Chennai.
“As diabetic patients are at a high risk of developing kidney failure, we wanted to know whether it would be possible to identify someone who had the risk of developing kidney failure, so that effective preventive steps could be taken before the individual fell ill,” said Kuppan Gokulakrishnan, assistant professor, Department of Neurochemistry, NIMHANS.
The researchers evaluated the efficiency of ASR using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI MS) from 555 people with varying levels of glucose intolerance. Along with people with normal glucose tolerance, pre-diabetic and newly diagnosed patients and even those with T2DM with MIC and MAC were part of the study.
They found that the ASR profile was lower in MIC and macroalbuminuria (MAC), suggesting that it had the potential to be used as an early diagnostic marker. The study was able to correctly identify 72% of MIC and 91% of MAC, respectively, among the patients.
“Early diagnosis of DN using a sensitive biomarker such as ASR is beneficial, to detect the onset of DN and to prevent or delay the progression into overt nephropathy. Our work is proof of concept that shows the use of ASR for assessing progressive DN, and this could aid future studies to understand the biology of nephropathy and the search for new treatments,” said Dr. Gokulakrishnan.
“Dimethylarginines (DMAs) are susceptible to protein binding, which may result in differential recovery for normal and proteinuric urine samples. Therefore, any quantitative estimation of these biomarkers and eventually meaningful clinical interpretations would have to take this into account as urine from patients with kidney disease has significant protein content. Estimation of their ratios using our approach offers a robust alternative to individual quantitative measurements. In this context, the decreased ASR in patients with MIC and MAC in our study is an important finding,” said Venkateswarlu Panchagnula from CSIR-NCL.
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