Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD

Am J Nephrol. 2011;33(5):469-76. doi: 10.1159/000327599. Epub 2011 Apr 21.

Abstract

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antioxidants / metabolism
  • Creatinine / urine
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Inflammation
  • Kidney / drug effects*
  • Kidney Failure, Chronic / drug therapy*
  • Male
  • Middle Aged
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / therapeutic use
  • Oxidative Stress
  • Placebos
  • Time Factors

Substances

  • Antioxidants
  • Placebos
  • Oleanolic Acid
  • Creatinine
  • methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate