The Clinical Effectiveness of Anti-TGF-β Therapy in Chronic Kidney Disease: A Systematic Review of Western and Traditional Chinese Medicine

Background: Chronic kidney disease (CKD) affects approximately 1.7 million Australians, with one in three individuals exhibiting associated risk factors. Despite its high prevalence, treatment options remain limited, underscoring the urgent need for novel therapeutic strategies to prevent progression to end-stage renal disease (ESRD). Transforming growth factor-beta (TGF-β), a key cytokine in fibrosis, has emerged as a potential therapeutic target, yet its clinical efficacy and safety remain uncertain. Methods: This review critically evaluates the effectiveness and safety of anti-TGF-β therapy in mitigating renal dysfunction and preventing ESRD, while also exploring the role of traditional Chinese medicine (TCM) in CKD management. A systematic search following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines identified six clinical trial articles and 14 clinical trials. Results: Among these, three were still in recruitment with unpublished results, and two failed to report findings. Notably, two randomized controlled trials (RCT) found no significant improvement in renal function with anti-TGF-β therapy, raising concerns about its clinical applicability. However, a pilot study and an RCT on Pirfenidone, an antifibrotic agent with TGF-β inhibitory properties, demonstrated significant reductions in the estimated glomerular filtration rate (eGFR) decline. Pre-clinical studies suggest antifibrotic potential, but clinical trials have yielded inconsistent results. Furthermore, emerging evidence indicates that TGF-β inhibition may exacerbate inflammation, potentially worsening renal function. Conclusion: These concerns highlight the critical need for well-designed clinical trials to validate both efficacy and safety. Given these limitations, TCM has garnered increasing interest for its renoprotective effects. However, further large-scale RCTs and mechanistic studies are essential to establish its therapeutic potential and facilitate their integration into evidence-based CKD treatment.