Researchers from The University of California, San Diego School of Medicine have published new metabolomics research that uncovers a novel, characteristic and highly consistent biochemical signature in urine associated with diabetic kidney disease. The findings, which form a foundation of ClinMet’s proprietary Clinical Metabolomics platform, have implications for the identification of clinically useful biomarkers for kidney function and for sharpening drug development and clinical trials related to chronic kidney disease, as well as to diabetes, obesity and cardiovascular disease.
The new research, authored by U.C. San Diego professor and ClinMet scientific founder, Kumar Sharma, M.D., F.A.H.A (Director of the Center for Renal Translational Medicine, Division of Nephrology-Hypertension and the Institute of Metabolomic Medicine) and colleagues, appears online in the Journal of the American Society of Nephrology. ClinMet has an exclusive license to use this set of metabolites in drug development and other applications, based on patents filed by UC San Diego.
The researchers quantified 94 urine metabolites in subjects with diabetes (type 1 or type 2) and chronic kidney disease (CKD), subjects with diabetes but no kidney disease, and healthy controls. They found that 13 of the metabolites were significantly different in those with disease compared to healthy controls (p values between 10-3 to 10-18), and 12 of 13 remained highly significant when compared to patients with type 1 or type 2 diabetes and no CKD. Moreover, 12 of the 13 metabolites were linked to mitochondrial metabolism and suggested global suppression of mitochondrial activity in the subjects with CKD relative to healthy individuals. This conclusion is in sharp contrast to prevailing beliefs about excess mitochondrial activity having a causal relationship to diabetic complications. The conclusions based on the urine metabolomic studies were independently validated based on protein and DNA analysis, indicating reduced mitochondrial content in the kidneys of patients with diabetic kidney disease.
“It is clear from this study that urine- and plasma-based metabolomics can be a rich source of biomarkers for understanding and treating diabetic kidney disease and possibly for related cardiovascular complications,” said Dr. Sharma. “This approach also offers direct insights into biochemical pathways linked to kidney dysfunction.”
Power of Clinical Metabolomics
“Genomics can help predict overall disease risk or a patient’s potential response to a drug, but cannot capture the effects that changes in diet, environmental factors, or other illnesses have on disease progression or improvement,” said Yesh Subramanian, President, Chief Executive Officer and co-founder of ClinMet. “Clinical metabolomics, in contrast, lets us quickly see biochemically what is happening in specific disease pathways over time and in the context of other factors affecting a patient’s health, including drug therapy. This makes clinical metabolomics a highly actionable platform for translational research and drug development.”
“We see clinical metabolomics enabling our pharmaceutical and biotech customers to effectively implement precision medicine today,” Mr. Subramanian noted. “The ability to predict which patients are likely to better respond to specific treatments holds immense promise for sharpening Phase 2 and 3 clinical trials now, and for improving clinical medicine in the future.”