title: Effect of bardoxolone methyl on kidney function in patients with T2D and Stage 3b-4 CKD.
abstract: OBJECTIVE
  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.
authors.affiliation: Renal Associates, PA, San Antonio, Tex., USA.
authors.forename: Pablo E
authors.initials: PE
authors.lastname: Pergola
authors.forename: Melissa
authors.initials: M
authors.lastname: Krauth
authors.forename: J Warren
authors.initials: JW
authors.lastname: Huff
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Ferguson
authors.forename: Stacey
authors.initials: S
authors.lastname: Ruiz
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Meyer
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
mesh_terms: D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007249:Inflammation; D007668:Kidney / Q000187:drug effects*; D007676:Kidney Failure, Chronic / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018384:Oxidative Stress; D010919:Placebos; D013997:Time Factors
chemical_list: D000975:Antioxidants; D010919:Placebos; D009828:Oleanolic Acid; D003404:Creatinine; C445068:bardoxolone methyl