Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Effect of bardoxolone methyl on the urine albumin-to-creatinine ratio in patients with type 2 diabetes and stage 4 chronic kidney disease

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Improvements in albuminuria and chronic kidney disease progression with the appetite suppressant lorcaserin

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Progression of diabetic kidney disease and trajectory of kidney function decline in Chinese patients with Type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. U-shaped dietary sodium-associated incidence of chronic kidney disease cautions against salt overrestriction in hypertension

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. YKL-40 in dialysis patients: another candidate in the quest for useful biomarkers in nephrology

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Lowering LDL cholesterol reduces cardiovascular risk independently of presence of inflammation

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Inflammation Leads the Way on the ROADMAP to Diabetic Kidney Disease

    Research output: Contribution to journalEditorialResearchpeer-review

  3. Prognostic value of ratio of transmitral early filling velocity to early diastolic strain rate in patients with Type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  • Peter Rossing
  • Geoffrey A Block
  • Melanie P Chin
  • Angie Goldsberry
  • Hiddo J L Heerspink
  • Peter A McCullough
  • Colin J Meyer
  • David Packham
  • Pablo E Pergola
  • Bruce Spinowitz
  • Stuart M Sprague
  • David G Warnock
  • Glenn M Chertow
View graph of relations

Bardoxolone methyl attenuates inflammation by inducing nuclear factor erythroid-derived 2-related factor 2 and suppressing nuclear factor κB. The Bardoxolone Methyl Evaluation in Patients With Chronic Kidney Disease and Type 2 Diabetes (BEACON) trial was a phase 3 placebo-controlled, randomized, double-blind, parallel-group, international, multicenter trial in 2185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease. BEACON was terminated because of safety concerns, largely related to a significant increase in early heart failure events in patients randomized to bardoxolone methyl. Bardoxolone methyl resulted in increased estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio. Herein, we present post hoc analyses characterizing the relation between the urine albumin-to-creatinine ratio and eGFR. The urine albumin-to-creatinine ratio and eGFR were assessed every four weeks through Week 12, followed by assessments every eight weeks thereafter, and 4 weeks after the last dose of bardoxolone methyl was administered. The initial increases in urine albumin-to-creatinine ratio observed in patients randomized to bardoxolone methyl were attenuated after six months. Multivariable regression analysis identified baseline eGFR and eGFR over time as the dominant factors associated with change in the urine albumin-to-creatinine ratio. Relative to placebo, bardoxolone methyl resulted in a significant decrease in albuminuria when indexed to eGFR (least-squared means: −0.035 [95% confidence interval −0.031 to −0.039]). Thus, among patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl, changes in albuminuria are directly related to changes in eGFR, challenging the conventional construct that increases in albuminuria universally reflect kidney injury and denote harm.

Original languageEnglish
JournalKidney International
Volume96
Issue number4
Pages (from-to)1030-1036
Number of pages7
ISSN0085-2538
DOIs
Publication statusPublished - 1 Oct 2019

    Research areas

  • albuminuria, chronic kidney disease, diabetic nephropathy, oxidative stress

ID: 57722506