Chuan Huang Fang combining reduced glutathione in treating acute kidney injury (grades 1–2) on chronic kidney disease (stages 2–4): A multicenter randomized controlled clinical trial

Abstract

Lack of effective drugs for acute kidney injury (AKI) grades 1–2 is a crucial challenge in clinic. Our previously single-center clinical studies indicated Chuan Huang Fang (CHF) might have nephroprotection in AKI on chronic kidney disease (CKD) (A on C) patients by preventing oxidant damage and inhibiting inflammation. Reduced glutathione (RG) has recently been shown to increase the clinical effectiveness of high-flux hemodialysis among patients with severe AKI. In this multicenter randomized controlled clinical study, we designed a new protocol to assess the efficacy and safety of CHF combining RG in patients with A on C. We also explored therapeutic mechanisms from renal fibrosis biomarkers. 98 participants were randomly and equally divided into the RG and RG + CHF subgroups. The RG and RG + CHF groups received general treatments with RG and a combination of RG and CHF, respectively. The therapy lasted for 2 weeks. In this study, the primary assessment result was a difference in the slope of serum creatinine (Scr) over the course of 2 weeks. The secondary evaluation outcomes were alterations in blood urea nitrogen (BUN), uric acid (UA), estimated glomerular filtration rate (eGFR), urinary AKI biomarkers, renal fibrosis biomarkers (transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF)), and traditional Chinese medicine (TCM) symptoms. Furthermore, vital signs and adverse events (AEs) were observed. Both groups had a slower renal function decline after treatment than before treatment. Compared with RG group, more reductions of Scr, BUN, UA, and better improvement of eGFR were observed in RG + CHF group (p < 0.05). Additionally, the levels of urinary AKI biomarkers, renal fibrosis biomarkers, and TCM syndromes were decreased in RG + CHF group versus RG group (p < 0.05). No significant between-group differences were observed of AEs. We thus concluded this novel therapy of CHF combining RG might be a useful method for treating A on C patients.

Bibliometric Analysis of the Relationship between Gut Microbiota and Chronic Kidney Disease from 2001–2022

“…CKD poses a significant global public health challenge, affecting the quality of life of affected individuals and exerting an economic burden on society. [26,27] Diverse etiologies contribute to the development of CKD, including immune the Clinical Journal of the American Society of Nephrology (1003) and the Journal of the American Society of Nephrology (881). Since most journals were based on the United States dollar, the USA had a powerful influence in the field.…”

“…CKD poses a significant global public health challenge, affecting the quality of life of affected individuals and exerting an economic burden on society. [26,27] Diverse etiologies contribute to the development of CKD, including immune inflammation, metabolic dysregulation, obstruction, and other systemic diseases, ultimately leading to renal fibrosis. [14,28] Renal fibrosis causes irreversible kidney damage, accelerating CKD progression.…”

“…[14,28] Renal fibrosis causes irreversible kidney damage, accelerating CKD progression. [26,29] Recent evidence [30][31][32][33] has identified gut microbiota as a regulatory factor in the development of CKD. Moreover, the gut microbiota composition of patients with CKD differs significantly from that of healthy individuals, and changes in gut microbiota composition may indicate CKD severity or progression.…”

The Molecular Mechanism and Therapeutic Strategy of Cardiorenal Syndrome Type 3

“…TCM formula can also improve AKI. A multicenter randomized controlled clinical trial showed that Chuan Huang Fang formula combined with reduced glutathione can be used to treat AKI (1-2 grades) in CKD patients (2-4 stages) [188]. In addition, Zou et al [189] showed that intestinal flora mediates the protective effect of Qiong-Yu-Gao, a TCM formula, on cisplatin induced AKI by increasing the production of SCFA, thereby inhibiting the expression and activity of histone deacetylase, and reducing the accumulation of uremic toxins.…”

Exploring therapeutic mechanisms of Chuan Huang Fang-II in the treatment of acute kidney injury on chronic kidney disease patients from the perspective of lipidomics

“…Historically, in the absence of renal replacement therapy (RRT), traditional Chinese medicine (TCM) has been employed to treat kidney disorders in ancient times. Chuan Huang Fang (CHF) is an empirical prescription for the treatment of A on C formulated by Professor Gong Xuezhong at the Shanghai Municipal Hospital of Traditional Chinese Medicine [ 4 , 5 ]. Our previous single-center clinical studies [ 6–8 ] have suggested that CHF may confer renal protective benefits in patients with A on C by reducing oxidative damage and inflammatory responses.…”