Therapeutic potential of Astragalus-based Eefooton in patients with chronic kidney disease: from clinical to bench study

Objective: Chronic kidney disease (CKD) is a global health concern, and recent clinical evidence suggests the potential of traditional Chinese medicine (TCM) to slow CKD progression. This offers alternative strategies for CKD patients, mitigating risks related to polypharmacy and adverse drug reactions. Our self-controlled, prospective study aims to assess the impact of Eefooton (EFT), a TCM-based regimen, on kidney health in stage 3-5 CKD patients. Additionally, we conduct a cell culture study to explore the potential mechanisms of EFT in protecting renal function. Materials and methods: Between 2021 and 2022, 75 stage 3-5 CKD patients (56% males; mean age 68.20y) at Kaohsiung Veterans General Hospital and Wu San-Chiang Medical Clinic received six months of EFT treatment alongside conventional CKD medications. The primary outcome assessed was the change in estimated glomerular filtration rate (eGFR) at 6 months, with secondary outcomes including kidney size and blood biomarker changes. Adverse events were monitored. In an in vitro study, EFT effects on HK-2 cell viability and clonogenicity, as well as analysis of apoptosis and fibrosis-related proteins through Western blot, were investigated. Results: Median eGFR significantly improved from 34.37 ± 13.58 to 42.47 ± 18.82 mL/min/1.73 m² (p < 0.001) at month 6 post-treatment. Notably, improvements were observed across different baseline CKD stages (stage 3: p < 0.001, stage 4: p = 0.037). Ultrasonography scans indicated a slight increase in mean kidney size. In vitro, EFT enhanced HK-2 cell viability and increased clonogenicity. Indoxyl sulfate exposure raised cleaved and total PARP-1 activity. Co-treatment with EFT and IS reduced cleaved PARP-1 activity. EFT decreased IS-induced expression of fibrosis-related proteins (α-smooth muscle actin) without affecting apoptosis-related proteins (Caspase 3). Conclusions: When combined with conventional CKD medications, EFT has shown effectiveness in enhancing kidney function in individuals with stage 3-5 CKD, with no reported safety concerns. The PARP-1 inhibition and anti-fibrosis properties of EFT present potential benefits in the context of CKD.