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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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. METHODS: 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. RESULTS: 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 ureanitrogen (-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. CONCLUSIONS: 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.
Authors: Eun-Hee Kim; Chuxia Deng; Michael B Sporn; Darlene B Royce; Renee Risingsong; Charlotte R Williams; Karen T Liby Journal: Cancer Prev Res (Phila) Date: 2011-09-20
Authors: Dick de Zeeuw; Tadao Akizawa; Paul Audhya; George L Bakris; Melanie Chin; Heidi Christ-Schmidt; Angie Goldsberry; Mark Houser; Melissa Krauth; Hiddo J Lambers Heerspink; John J McMurray; Colin J Meyer; Hans-Henrik Parving; Giuseppe Remuzzi; Robert D Toto; Nosratola D Vaziri; Christoph Wanner; Janet Wittes; Danielle Wrolstad; Glenn M Chertow Journal: N Engl J Med Date: 2013-11-09 Impact factor: 91.245
Authors: Melanie P Chin; George L Bakris; Geoffrey A Block; Glenn M Chertow; Angie Goldsberry; Lesley A Inker; Hiddo J L Heerspink; Megan O'Grady; Pablo E Pergola; Christoph Wanner; David G Warnock; Colin J Meyer Journal: Am J Nephrol Date: 2018-01-18 Impact factor: 3.754