Diabetic kidney disease (DKD) involves various pathogenic processes during progression to end stage renal disease, and activated metabolic pathways might be changing based on major pathophysiologic mechanisms as DKD progresses. In this study, nuclear magnetic resonance spectroscopy (NMR)-based metabolic profiling was performed in db/db mice to suggest potential biomarkers for early detection and its progression. We compared concentrations of serum and urinary metabolites between db/m and db/db mice at 8 or 20 weeks of age and investigated whether changes between 8 and 20 weeks in each group were significant. The metabolic profiles demonstrated significantly increased urine levels of glucose and tricarboxylic acid cycle intermediates at both 8 and 20 weeks of age in db/db mice. These intermediates also exhibited strong positive associations with urinary albumin excretion, suggesting that they may be potential biomarkers for early diagnosis. On the contrary, branched chain amino acid and homocysteine-methionine metabolism were activated early in the disease, whereas ketone and fatty acid metabolism were significantly changed in the late phase of the disease. We demonstrated phase-specific alterations in metabolites during progression of DKD. This study provides insights into perturbed mechanisms during evolution of the disease and identifies potential novel biomarkers for DKD.
Bibliographical noteFunding Information:
This study was supported by the National Research Foundation (NRF) of Korea (No. 2013M3A9B6046418 ), National Research Council of Science and Technology ( DRC-14-1-KBSI and CAP-12-2-KBSI ), and Korea Basic Science Institute ( C38705 ). It was also supported by the NRF of Korea (MSIP, NRF-2014R1A2A1A11050945 and MSIP, NRF-2015R1A2A2A01003167 ), as well as by a grant ( 2015F-6 ) from the Korean Diabetes Association .
All Science Journal Classification (ASJC) codes
- Molecular Biology