Chen Ling, Ye Zi, Wang Danjun, Liu Jianlian, Wang Qian, Wang Chen, Xu Bing, Gong Xuezhong
Department of Nephrology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2022 Oct 3;13:969107. doi: 10.3389/fphar.2022.969107. eCollection 2022.
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- (TGF- ), 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 ( < 0.05). Additionally, the levels of urinary AKI biomarkers, renal fibrosis biomarkers, and TCM syndromes were decreased in RG + CHF group versus RG group ( < 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.
1-2级急性肾损伤（AKI）缺乏有效的治疗药物是临床上的一项关键挑战。我们之前的单中心临床研究表明，川芎方（CHF）可能通过预防氧化损伤和抑制炎症，对慢性肾脏病（CKD）基础上的急性肾损伤（A on C）患者具有肾脏保护作用。最近有研究表明，还原型谷胱甘肽（RG）可提高重度AKI患者高通量血液透析的临床疗效。在这项多中心随机对照临床研究中，我们设计了一种新方案，以评估CHF联合RG治疗A on C患者的疗效和安全性。我们还从肾纤维化生物标志物方面探讨了治疗机制。98名参与者被随机且平均分为RG组和RG + CHF组。RG组和RG + CHF组分别接受RG及RG与CHF联合的常规治疗。治疗持续2周。在本研究中，主要评估结果是2周内血清肌酐（Scr）斜率的差异。次要评估指标包括血尿素氮（BUN）、尿酸（UA）、估算肾小球滤过率（eGFR）、尿AKI生物标志物、肾纤维化生物标志物（转化生长因子-β（TGF-β）、结缔组织生长因子（CTGF））以及中医症状的变化。此外，还观察了生命体征和不良事件（AE）。两组治疗后肾功能下降速度均较治疗前减慢。与RG组相比，RG + CHF组Scr、BUN、UA降低更多，eGFR改善更明显（P < 0.05）。此外，RG + CHF组尿AKI生物标志物、肾纤维化生物标志物水平及中医证候较RG组降低（P < 0.05）。两组间AE无显著差异。因此，我们得出结论，CHF联合RG这种新疗法可能是治疗A on C患者的有效方法。
