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.

慢性肾脏病（CKD）已成为世界范围内的主要公共卫生问题，对数百万人的生活质量产生重大影响。长期阻塞性尿毒症是CKD的重要原因。我们假设可以通过生物流体的代谢组学分析发现早期阻塞性肾病的生物标志物。对大鼠进行单侧输尿管闭塞（UUO）手术以诱导肾间质纤维化。假手术大鼠用作对照。通过基于UPLC-MS的代谢组学方法分析血浆和尿液代谢物。在不同时间点，UUO大鼠和对照组之间发现了显着的代谢谱分离。术后第一天鉴定出13种血浆代谢物和14种尿液代谢物。改变的代谢途径包括甘油磷脂代谢，色氨酸代谢，谷氨酸代谢和嘌呤代谢。我们进一步鉴定了一组五种血浆生物标志物，它们为梗阻性肾病的早期诊断提供了良好的诊断性能（发现组和验证组中1.0曲线以下的区域）。这些发现表明，可以在基于血浆代谢组学的动物模型中诊断出早期阻塞性肾病，血浆代谢组学是表征代谢紊乱的有力工具。这种方法具有很强的临床翻译潜力。发现组和验证组中的0）用于梗阻性肾病的早期诊断。这些发现表明，可以在基于血浆代谢组学的动物模型中诊断出早期阻塞性肾病，血浆代谢组学是表征代谢紊乱的有力工具。这种方法具有很强的临床翻译潜力。发现组和验证组中的0）用于梗阻性肾病的早期诊断。这些发现表明，可以在基于血浆代谢组学的动物模型中诊断出早期阻塞性肾病，血浆代谢组学是表征代谢紊乱的有力工具。这种方法具有很强的临床翻译潜力。