Biomarkers of obstructive nephropathy using a metabolomics approach in rat.

Chronic kidney disease (CKD) has become a major public health problem worldwide and has a great impact on the quality of life of millions of people. Long-term obstructive uropathy is an important cause of CKD. We hypothesized diagnostic biomarkers for early stage obstructive nephropathy can be discovered by metabolomic profiling of biofluid. Unilateral ureteral occlusion (UUO) surgery was performed on rats to induce renal interstitial fibrosis. Sham-operated rats were used as controls. Plasma and urine metabolites were analyzed by UPLC-MS based metabolomic approach. Significant metabolic profiling separations were found between UUO rats and controls at different time points. 13 differential plasma metabolites and 14 differential urine metabolites were identified at the first postoperative day. The altered metabolic pathways included glycerophospholipid metabolism, tryptophan metabolism, glutamate metabolism and purine metabolism. We further identified a panel of five plasma biomarkers which offer good diagnostic performance (areas under the curve of 1.0 in the discovery set and validation set) for early diagnosis of obstructive nephropathy. These findings demonstrate that early stage obstructive nephropathy can be diagnosed in an animal model based on plasma metabolomics which is a powerful tool for characterizing metabolic disturbances. This method has strong potential for clinical translation.