Renal Associates, PA, San Antonio, Tex., USA.
Am J Nephrol. 2011;33(5):469-76. doi: 10.1159/000327599. Epub 2011 Apr 21.
BACKGROUND/AIMS: Bardoxolone methyl, a novel synthetic triterpenoid, induces Nrf2, a transcription factor known to play a key role in decreasing oxidative stress and the production of pro-inflammatory molecules.
This exploratory multi-center, open-label study assessed the clinical activity and safety of bardoxolone methyl in 20 patients with moderate to severe chronic kidney disease and type 2 diabetes. Patients received 25 mg of bardoxolone methyl daily for 28 days, followed by 75 mg daily for another 28 days.
The study achieved its primary efficacy endpoint, as demonstrated by a significant increase from baseline in estimated glomerular filtration rate (eGFR) of 7.2 ml/min/1.73 m2 (p < 0.001). Improvements were seen in approximately 90% of patients and showed a dose- and time-dependent increase in eGFR. The eGFR change paralleled a significant reduction in serum creatinine (-0.3 mg/dl) and blood urea nitrogen (-4.9 mg/dl), along with an increase in creatinine clearance (+14.6 ml/min/1.73 m2), without a change in the 24-hour creatinine excretion rate. Markers of vascular injury and inflammation were improved by treatment with bardoxolone. No life-threatening adverse events or drug-related serious adverse events were reported.
The results describe an apparent increase in kidney function following relatively short-term treatment with bardoxolone methyl, a promising new agent that warrants placebo-controlled studies to define its long-term effects on renal function.
背景/目的：Bardoxolone 甲酯，一种新型合成三萜类化合物，可诱导 Nrf2，这是一种已知在降低氧化应激和促炎分子产生方面发挥关键作用的转录因子。
这项探索性的多中心、开放性标签研究评估了 Bardoxolone 甲酯在 20 名患有中重度慢性肾脏病和 2 型糖尿病的患者中的临床活性和安全性。患者接受 Bardoxolone 甲酯 25mg 每日一次，共 28 天，然后每日 75mg，再持续 28 天。
该研究达到了其主要疗效终点，表现为估计肾小球滤过率（eGFR）从基线显著增加 7.2ml/min/1.73m2（p<0.001）。约 90%的患者出现改善，并且 eGFR 呈剂量和时间依赖性增加。eGFR 的变化与血清肌酐（-0.3mg/dl）和血尿素氮（-4.9mg/dl）的显著降低以及肌酐清除率（+14.6ml/min/1.73m2）的增加相平行，而 24 小时肌酐排泄率没有变化。Bardoxolone 治疗可改善血管损伤和炎症标志物。没有报告危及生命的不良事件或与药物相关的严重不良事件。
这些结果描述了 Bardoxolone 甲酯治疗后肾功能明显增加，这是一种很有前途的新药，需要进行安慰剂对照研究来确定其对肾功能的长期影响。
