Study discovered: Metabolites altered in chronic kidney disease


According to National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK), Chronic Kidney disease (CKD) affects 1 in 7 people in the United States. People with CKD have a very high-risk of cardiovascular disease leading to kidney failure.

Stein Hallan said, “We analyzed these small molecules in the blood and urine of non-diabetic patients with chronic kidney disease and compared the results to samples obtained from a group of healthy individuals." "Importantly, our study identified that a group of molecules called tri-carboxylic acid (TCA) cycle metabolites are significantly affected by chronic kidney disease."

Chronic kidney disease, fatigue, and metabolism

Kumar Sharma from Renal Precision Medicine at UT Health San Antonio said that TCA cycle is a method, where fuel molecules are converted into energy. This process is seen in mitochondria (energy cell). Mitochondrial dysfunction leads to problems in TCA cycle which causes CKD. Dr. Hallan said, "Typically, patients with more advanced stages of CKD suffer from severe fatigue, and many other organs (muscles, brain, gut, and others) are also not functioning well.” "The clinical picture indicates that there is a general underlying defect in the mitochondrial function of these patients."

In 2013, a team from UC San Diego of the clinical investigators published few papers. These papers supported mitochondrial dysfunction, an essential mechanism in diabetes and other kidney diseases. A new study observed in CKD patients, expression of genes that regulate the TCA cycle was significantly reduced compared to healthy individuals.

Molecular clues to kidney disease therapies

Researchers hope that a new breakthrough therapy could arise from these insights.

Dr. Sharma said "Metabolomics, the analysis of small molecules in biological samples, has revealed numerous abnormalities in the blood of uremic patients, whose kidneys are unable to eliminate the body's waste products. Further exploration of the TCA cycle, using metabolomics, may identify novel therapeutic targets for CKD and in turn, may help us to evaluate the effects of promising interventions."

Center for Renal Precision Medicine

Dr. Sharma recently was awarded a $1.4 million Translational STARs award to establish the Center for Renal Precision Medicine at UT Health San Antonio. Dr. Sharma is also the vice chairman of research in the Department of Medicine of the Joe R. & Teresa Lozano Long School of Medicine and occupies the L. David Hillis, M.D. Endowed Chair in Medicine. He submitted an invention to the Office of Technology Commercialization at UT Health San Antonio.

From the study, researchers concluded that significantly the metabolomics were altered in chronic kidney disease .Further studies shows by using TCA cycle; metabolomics could identify therapeutic targets for CKD. In addition, it may help to evaluate the new interventions.