Bardoxolone Methyl Improves Kidney Function in Patients with Chronic Kidney Disease Stage 4 and Type 2 Diabetes: Post-Hoc Analyses from Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes Study

Am J Nephrol. 2018;47(1):40-47. doi: 10.1159/000486398. Epub 2018 Jan 18.


Background: Increases in measured inulin clearance, measured creatinine clearance, and estimated glomerular filtration rate (eGFR) have been observed with bardoxolone methyl in 7 studies enrolling approximately 2,600 patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). The largest of these studies was Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes (BEACON), a multinational, randomized, double-blind, placebo-controlled phase 3 trial which enrolled patients with T2D and CKD stage 4. The BEACON trial was terminated after preliminary analyses showed that patients randomized to bardoxolone methyl experienced significantly higher rates of heart failure events. We performed post-hoc analyses to characterize changes in kidney function induced by bardoxolone methyl.

Methods: Patients in -BEACON (n = 2,185) were randomized 1: 1 to receive once-daily bardoxolone methyl (20 mg) or placebo. We compared the effects of bardoxolone methyl and placebo on a post-hoc composite renal endpoint consisting of ≥30% decline from baseline in eGFR, eGFR <15 mL/min/1.73 m2, and end-stage renal disease (ESRD) events (provision of dialysis or kidney transplantation).

Results: Consistent with prior studies, patients randomized to bardoxolone methyl experienced mean increases in eGFR that were sustained through study week 48. Moreover, increases in eGFR from baseline were sustained 4 weeks after cessation of treatment. Patients randomized to bardoxolone methyl were significantly less likely to experience the composite renal endpoint (hazards ratio 0.48 [95% CI 0.36-0.64]; p < 0.0001).

Conclusions: Bardoxolone methyl preserves kidney function and may delay the onset of ESRD in patients with T2D and stage 4 CKD.

Keywords: Bardoxolone methyl; eGFR.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Disease Progression
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Heart Failure / chemically induced
  • Heart Failure / epidemiology
  • Humans
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / pathology
  • Kidney Failure, Chronic / physiopathology
  • Kidney Failure, Chronic / prevention & control*
  • Kidney Transplantation / statistics & numerical data
  • Male
  • Middle Aged
  • Oleanolic Acid / administration & dosage
  • Oleanolic Acid / adverse effects
  • Oleanolic Acid / analogs & derivatives*
  • Renal Dialysis / statistics & numerical data
  • Treatment Outcome


  • Oleanolic Acid
  • bardoxolone methyl