Bardoxolone Methyl and Kidney Function in CKD with Type 2 Diabetes
Top Cited Papers
- 28 July 2011
- journal article
- research article
- Published by Massachusetts Medical Society in New England Journal of Medicine
- Vol. 365 (4), 327-336
- https://doi.org/10.1056/nejmoa1105351
Abstract
Chronic kidney disease (CKD) associated with type 2 diabetes is the leading cause of kidney failure, with both inflammation and oxidative stress contributing to disease progression. Bardoxolone methyl, an oral antioxidant inflammation modulator, has shown efficacy in patients with CKD and type 2 diabetes in short-term studies, but longer-term effects and dose response have not been determined. In this phase 2, double-blind, randomized, placebo-controlled trial, we assigned 227 adults with CKD (defined as an estimated glomerular filtration rate [GFR] of 20 to 45 ml per minute per 1.73 m2 of body-surface area) in a 1:1:1:1 ratio to receive placebo or bardoxolone methyl at a target dose of 25, 75, or 150 mg once daily. The primary outcome was the change from baseline in the estimated GFR with bardoxolone methyl, as compared with placebo, at 24 weeks; a secondary outcome was the change at 52 weeks. Patients receiving bardoxolone methyl had significant increases in the mean (±SD) estimated GFR, as compared with placebo, at 24 weeks (with between-group differences per minute per 1.73 m2 of 8.2±1.5 ml in the 25-mg group, 11.4±1.5 ml in the 75-mg group, and 10.4±1.5 ml in the 150-mg group; P2 of 5.8±1.8 ml, 10.5±1.8 ml, and 9.3±1.9 ml, respectively. Muscle spasms, the most frequent adverse event in the bardoxolone methyl groups, were generally mild and dose-related. Hypomagnesemia, mild increases in alanine aminotransferase levels, and gastrointestinal effects were more common among patients receiving bardoxolone methyl. Bardoxolone methyl was associated with improvement in the estimated GFR in patients with advanced CKD and type 2 diabetes at 24 weeks. The improvement persisted at 52 weeks, suggesting that bardoxolone methyl may have promise for the treatment of CKD. (Funded by Reata Pharmaceuticals; BEAM ClinicalTrials.gov number, NCT00811889.)This publication has 38 references indexed in Scilit:
- Can ACE Inhibitors and Angiotensin Receptor Blockers Be Detrimental in CKD Patients?Nephron Clinical Practice, 2011
- Chronic kidney disease: a public health priority and harbinger of premature cardiovascular diseaseJournal of Internal Medicine, 2010
- NADPH oxidases and angiotensin II receptor signalingMolecular and Cellular Endocrinology, 2009
- Aldosterone Antagonists for Preventing the Progression of Chronic Kidney DiseaseClinical Journal of the American Society of Nephrology, 2009
- Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trialThe Lancet, 2008
- Antihypertensive Therapy in the Presence of ProteinuriaAmerican Journal of Kidney Diseases, 2007
- Renal Outcomes in High-Risk Hypertensive Patients Treated With an Angiotensin-Converting Enzyme Inhibitor or a Calcium Channel Blocker vs a DiureticArchives of Internal Medicine, 2005
- Angiotensin-Receptor Blockade versus Converting–Enzyme Inhibition in Type 2 Diabetes and NephropathyNew England Journal of Medicine, 2004
- Chronic Kidney Disease and the Risks of Death, Cardiovascular Events, and HospitalizationNew England Journal of Medicine, 2004
- Leptin and renal diseaseAmerican Journal of Kidney Diseases, 2002