Astragalus membranaceus (AM), also known as Huangqi (黄芪)，is a prominent herb in Traditional Chinese Medicine (TCM), is widely utilized in the management of nephrotic syndrome (NS). Characterized by symptoms such as fluid overload, peripheral edema, and proteinuria, nephrotic syndrome is a complex renal condition. AM is a key component in many TCM formulations aimed at treating primary nephrotic syndrome. This review evaluates the evidence supporting AM’s immunoregulatory activities, its mechanisms of action in glomerular pathology, and the efficacy and safety of AM-containing TCM formulations compared to standard Western medicine (WM) treatments.

Mechanisms of Action: AM is believed to exert its effects through several mechanisms:

• Immunoregulation: AM modulates immune responses, potentially reducing inflammation and enhancing renal protection.
• Anti-inflammatory Effects: It impacts key cytokines involved in inflammation, such as IL-1, IL-6, IL-8, and TNF-α, thereby mitigating renal damage.
• Renal Protection: AM may help preserve renal function by reducing proteinuria and hyperlipidaemia, which are common in nephrotic syndrome.

Evidence from Clinical Studies: A comprehensive review of randomized controlled trials (RCTs) comparing AM-containing TCM formulations with standard WM treatments reveals the following findings:

• Biochemical Improvements: AM supplementation has been associated with significant improvements in biochemical markers, including a reduction in proteinuria, hyperlipidemia, and an increase in serum albumin levels.
• Renal Function: The addition of AM to standard WM treatment often results in preserved or improved renal function.
• Remission Rates: Patients receiving AM-containing TCM formulations show higher remission rates compared to those treated with standard WM alone.
• Inflammatory Markers: Significant reductions in inflammatory cytokines (IL-1, IL-6, IL-8, TNF-α) were observed in AM-treated groups versus those receiving steroid-alone treatments.
• Reduced Relapse Rates: Some studies indicate a lower incidence of relapse in patients treated with AM compared to control groups.
• Safety Profile: AM was generally well-tolerated with no significant difference in adverse events (AEs) or side effects compared to standard WM treatments. Dosages used in studies ranged from 9 to 30 grams per day, within the range recommended by the Chinese Pharmacopoeia.

Concerns regarding potential interactions between AM and immunosuppressive medications have been noted. In vitro studies yield mixed results, and the complexity of TCM formulations, which often include multiple herbs, adds to the challenge of isolating specific interactions. However, drug level monitoring for immunosuppressants such as cyclosporine and tacrolimus can help manage potential issues of drug exposure.

In conclusion, the available evidence supports the clinical benefit of Astragalus membranaceus as an adjunctive therapy in the management of primary nephrotic syndrome. While the Jadad scores of the RCTs reviewed are generally low, indicating a need for higher-quality studies, the consistent positive outcomes suggest that AM may enhance remission rates and improve disease markers without significantly increasing adverse effects. Further research with rigorous methodologies is warranted to better understand the long-term effects and optimal usage of AM in nephrotic syndrome management.

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