Should we increase GFR with bardoxolone in Alport syndrome?
Bardoxolone methyl is a semisynthetic oleanane triterpenoid, and it is thought to act by promoting the resolution of inflammation via activation of Nrf-2 and inhibition of NF k–light-chain enhancer of activated B cells. Initial phase 1 studies showed, as an incidental finding, that bardoxolone incre...
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| Format: | Journal article |
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American Society of Nephrology
2018
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| _version_ | 1797084041709617152 |
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| author | Baigent, C Lennon, R |
| author_facet | Baigent, C Lennon, R |
| author_sort | Baigent, C |
| collection | OXFORD |
| description | Bardoxolone methyl is a semisynthetic oleanane triterpenoid, and it is thought to act by promoting the resolution of inflammation via activation of Nrf-2 and inhibition of NF k–light-chain enhancer of activated B cells. Initial phase 1 studies showed, as an incidental finding, that bardoxolone increased eGFR, which generated interest in its potential as a drug to delay the progression of CKD. Subsequently, the 52-week Bardoxolone Methyl Treatment: Renal Function in CKD/Type 2 Diabetes (BEAM) Study, a phase 2, randomized trial of 227 patients with moderate to severe CKD (eGFR520–45 ml/min per 1.73 m2) and type 2 diabetes mellitus confirmed that bardoxolone produced dose-dependent elevations in eGFR: for example, participants allocated to a dose of 25 mg daily achieved an 8.2615-ml/min per 1.73m2 increase in eGFR at 24 weeks. However, the subsequent phase 3 trial, the Bardoxolone Methyl Evaluation in Patients with CKD and Type 2 DiabetesMellitus: The Occurrence of Renal Events (BEACON) Trial, with around 2000 patients with eGFR from 15 to < 30 ml/min per 1.73 m2 and diabetes mellitus was terminated prematurely by the independent data and safety monitoring committee due to an excess risk of hospitalization or death fromheart failure (relative risk, 1.83; 95% confidence interval, 1.32 to 2.55; P,0.001). |
| first_indexed | 2024-03-07T01:50:05Z |
| format | Journal article |
| id | oxford-uuid:99c831f2-e3de-4f6e-b323-7d14def4e0a9 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T01:50:05Z |
| publishDate | 2018 |
| publisher | American Society of Nephrology |
| record_format | dspace |
| spelling | oxford-uuid:99c831f2-e3de-4f6e-b323-7d14def4e0a92022-03-27T00:16:49ZShould we increase GFR with bardoxolone in Alport syndrome?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:99c831f2-e3de-4f6e-b323-7d14def4e0a9Symplectic Elements at OxfordAmerican Society of Nephrology2018Baigent, CLennon, RBardoxolone methyl is a semisynthetic oleanane triterpenoid, and it is thought to act by promoting the resolution of inflammation via activation of Nrf-2 and inhibition of NF k–light-chain enhancer of activated B cells. Initial phase 1 studies showed, as an incidental finding, that bardoxolone increased eGFR, which generated interest in its potential as a drug to delay the progression of CKD. Subsequently, the 52-week Bardoxolone Methyl Treatment: Renal Function in CKD/Type 2 Diabetes (BEAM) Study, a phase 2, randomized trial of 227 patients with moderate to severe CKD (eGFR520–45 ml/min per 1.73 m2) and type 2 diabetes mellitus confirmed that bardoxolone produced dose-dependent elevations in eGFR: for example, participants allocated to a dose of 25 mg daily achieved an 8.2615-ml/min per 1.73m2 increase in eGFR at 24 weeks. However, the subsequent phase 3 trial, the Bardoxolone Methyl Evaluation in Patients with CKD and Type 2 DiabetesMellitus: The Occurrence of Renal Events (BEACON) Trial, with around 2000 patients with eGFR from 15 to < 30 ml/min per 1.73 m2 and diabetes mellitus was terminated prematurely by the independent data and safety monitoring committee due to an excess risk of hospitalization or death fromheart failure (relative risk, 1.83; 95% confidence interval, 1.32 to 2.55; P,0.001). |
| spellingShingle | Baigent, C Lennon, R Should we increase GFR with bardoxolone in Alport syndrome? |
| title | Should we increase GFR with bardoxolone in Alport syndrome? |
| title_full | Should we increase GFR with bardoxolone in Alport syndrome? |
| title_fullStr | Should we increase GFR with bardoxolone in Alport syndrome? |
| title_full_unstemmed | Should we increase GFR with bardoxolone in Alport syndrome? |
| title_short | Should we increase GFR with bardoxolone in Alport syndrome? |
| title_sort | should we increase gfr with bardoxolone in alport syndrome |
| work_keys_str_mv | AT baigentc shouldweincreasegfrwithbardoxoloneinalportsyndrome AT lennonr shouldweincreasegfrwithbardoxoloneinalportsyndrome |