To determine the landmark metabolites and related metabolic pathways of the dampness-heat syndrome model in juvenile rats with immunoglobulin A nephropathy(IgAN) based on NMR-based metabolomics,and provide a theoretical basis to seek the optimal timing for drug intervention.Methods:Seventy-two 3-week-old male SD rats were enrolled and divided into a control group and a model group according to a random number table,with 36 rats in each group.The IgAN model was replicated in rats.The rats were weighed and urine samples were collected every week for routine urine and metabolomics tests for 12 weeks.Blood samples were collected in the 4th,6th,8th,10th,and 12th weeks for biochemical indicators,cytokines,and renal histopathological detection.Pattern recognition and multivariate statistical analysis in metabolomics were employed to screen out potential markers of hematuria dampness-heat syndrome in rats and construct corresponding metabolic pathways.The general conditions,biochemical indicators,cytokines,renal histopathology,etc.were compared to explore the time variation law.Results:Compared with the control group,the model group showed slowed rate of weight gain and dampness-heat syndrome from the 5th week; blood urine in the 6th week and proteinuria in the 8th week; increased biochemical indicators,such as TG,Chol,and Scr; proliferative changes in the mesangial area of the glomerulus,which were gradually aggravated in the 8th,10th,and 12th weeks; IgA deposition as shown by immunofluorescence; increased expression of NF-κB and TGF-β1 from the 6th and 10th weeks respectively,corresponding to the pathological changes in renal tissues.Metabolomics identified 14 potential markers and six main metabolic pathways,which showed a certain change over time.Conclusion:This study preliminarily explored the urine metabolomics markers and corresponding metabolic pathways associated with hematuria dampness-heat syndrome in traditional Chinese medicine(TCM),and suggested that the changes in urine metabolomics were earlier than other microscopic levels such as biochemistry,cytokines,and renal pathology,which laid the experimental foundation for further accurately determining the optimal timing of intervention with this disease.