The Therapeutic Effect And Metabolite Analysis Of Tripterygium Wilfordii Polyglycosides In Patients With CKD3-4 Diabetic Nephropathy

Objectives In patients with diabetic nephropathy with CKD stage 3-4 with large amounts of proteinuria,some with RAS inhibitors could not reduce proteinuria to the ideal level.Tripterygium glycosides have anti-inflammatory,immunomodulatory and albuminuria reducing effects..1.To observe the clinical efficacy and safety of tripterygium glycosides combined with RAS inhibitors in the treatment of CKD stage 3-4 diabetic nephropathy.2.Metabolomics method was used to analyze the changes of blood and urine metabolic pathway in patients with CKD stage 3-4 diabetic nephropathy treated with tripterygium glycosides.Methods From October 2018 to January 2019,in patients with diabetic nephropathy who were followed up in the outpatient clinic of Peking Union Medical College Hospital,15≤eGFR<60 ml/min/1.73m2 was selected,Patients who received treatment including RAS inhibitor and still had a large amount of proteinuria were treated with tripterygium polyglucoside;patients matched with patients with tripterygium sinensis in the gender,age,urine protein levels,and creatinine were selected from the follow-up diabetic nephropathy cohort as a control group.The changes of the two groups before and after treatment were compared to evaluate the efficacy and safety of tripterygium glycosides.2.Collection of blood and urine samples before treatment and after 1 month of treatment in tripterygium glycosides treatment group,using UPLC-LTQ-Orbitrap high resolution mass spectrometry,detected the metabolites.The differential variables were analyzed by MetaboAnalyst software for metabolic pathway analysis.Results 1.A total of 28 patients were included,14 patients in the tripterygium glycosides group and 14 patients in the control group.There were no significant differences in the baseline levels between the two groups.After 1 month,the urinary protein of the tripterygium glycosides group decreased significantly(decline rate 44.7%P<0.05),and the control group decreased by 35.9%(P<0.05).There was a significant difference between the two groups(P=0.03).The level of leukocyte in the tripterygium glycosides group decreased slightly,but it was still in the normal range;the albumin level also decreased slightly.2.In the analysis of changes in urine metabolites,18 differential metabolic pathways were found,in which leukotriene metabolism,peroxidase fatty acid metabolism,and eicosapentaenoic acid metabolic pathway were associated with inflammation and oxidative stress.In the analysis of changes in blood metabolites,there are similar metabolic pathway differences with urine.Conclusions 1.The use of tripterygium glycosides in patients with diabetic nephropathy with CKD 3-4 and large amounts of proteinuria can further reduce urinary protein levels and have a protective effect on the kidneys.2.The effect of tripterygium glycosides on reducing urinary protein in patients with diabetic nephropathy may be related to the regulation of inflammation and oxidative stress.