Efficacy of Tripterygium glycosides in immune-mediated kidney diseases as a immunomodulation drug in combination with conventional immunosuppressive agents: A systematic review and meta-analysis of randomized controlled trials

Yao-tan Li^1,2Jinyi Hou¹Xiaochang Wu¹Chang Liu²Mengqi Zhou³Shijia Lin¹Weijing Liu¹Yao-Xian Wang^2*Huijuan Zheng^1*

• ¹Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
• ²Beijing University of Chinese Medicine, Beijing, Beijing Municipality, China
• ³Beijing Puren Hospital, Dongcheng, Beijing Municipality, China

Study design: Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs).Methods: We searched nine electronic databases for articles from January 1, 2014 to June 1, 2025.We included the RCTs comparing TG combined with immunosuppressive agents versus immunosuppressive agents alone. Meta-analysis was performed according to the Cochrane Handbook.Results: Thirty-six RCTs were included, involving 3455 patients with various conditions such as membranous nephropathy (MN), IgA nephropathy (IgAN), primary nephrotic syndrome (PNS) and others. The combined use of TG and immunosuppressive agents differs from the use of immunosuppressive agents alone in terms of clinical efficacy (RR = 1.26; 95%CI: 1.22 to 1.30), improvement in serum creatinine (Cr) (SMD = -0.86; 95%CI: -1.11 to -0.61), blood urea nitrogen (BUN) (SMD = -0.68; 95%CI: -1.05 to -0.31), 24-hour urinary total protein (24h-UTP) (SMD = -0.93; 95%CI: -1.13 to -0.74), and serum albumin (ALB) (SMD = 1.30; 95%CI: 1.08 to 1.52). However, there is no statistically significant difference in the improvement of total cholesterol (TC) (SMD = -0.62; 95%CI:.-1.39 to 0.16). In terms of overall safety, the combination therapy shows a statistically significant difference compared to the use of immunosuppressive agents alone (RR =0.72; 95%CI: 0.58 to 0.90), but no differences were observed in gastrointestinal issues, liver damage, leukopenia, and infections. Additionally, our analysis found that the combination therapy has a significant advantage over the use of immunosuppressive agents alone in reducing the recurrence rate (RR = 0.21; 95%CI: 0.10 to 0.44). In terms of mechanisms, the final results indicate that there are differences in interleukin-6 (IL-6) and C-reactive protein (CRP) levels between the two groups, while no differences were observed in interleukin-1 (IL-1) and tumor necrosis factor (TNF-α). However, treatment course, TG dosage, and sample size are important factors influencing the results.Conclusion: Our study suggests that the combination of TG with immunosuppressive agents offers more pronounced efficacy in treating immune mediated kidney diseases, without increasing the incidence of adverse reactions. However, our findings may be limited by the quality of the existing studies. High-quality RCTs are needed to provide more accurate evidence.