Trial reportClinical and translational science2021
Effects of Bardoxolone Methyl on Hepatic Enzymes in Patients with Type 2 Diabetes Mellitus and Stage 4 CKD.
Trial report in Clinical and translational science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Calciphylaxis in chronic kidney disease: a systematic review of pathomechanisms and risk factors for calcific uremic arteriolopathy.Renal failure · 2026Pooled it
- Antioxidants for adults with chronic kidney disease.The Cochrane database of systematic reviews · 2023Pooled it
- Safety and Efficacy of Omaveloxolone in Friedreich Ataxia (MOXIe Study).Annals of neurology · 2021Trial
- PEBP4 alleviates muscle wasting in lung cancer cachexia via KEAP1-NRF2-mediated redox homeostasis.Cell death & disease · 2026Article
- The AMPK/NRF2/FOXO Axis in CKD-Molecular and Clinical Perspectives.Antioxidants (Basel, Switzerland) · 2026Review
- Nuclear factor erythroid 2-related factor: potential use as a therapeutic strategy for viral infections.Archives of microbiology · 2026Review
- Mitochondrial dysfunction: the hidden catalyst in chronic kidney disease progression.Renal failure · 2025Review
- Non-Electrophilic Activation of NRF2 in Neurological Disorders: Therapeutic Promise of Non-Pharmacological Strategies.Antioxidants (Basel, Switzerland) · 2025Review
- Managing Aminotransferase Elevations in Patients with Friedreich Ataxia Treated with Omaveloxolone: A Review and Expert Opinion on Use Considerations.Neurology and therapy · 2025Review
- The Role of Nrf2 in the Regulation of Periodontitis, Peri-implantitis, Dentin Infection, and Apical Periodontitis.Biological procedures online · 2025Review
- Modulation of Lonp1 Activity by Small Compounds.Biomolecules · 2025Review
- Antioxidant-Rich Functional Foods and Exercise: Unlocking Metabolic Health Through Nrf2 and Related Pathways.International journal of molecular sciences · 2025Review
- Nrf2 Signaling Pathway as a Key to Treatment for Diabetic Dyslipidemia and Atherosclerosis.International journal of molecular sciences · 2024Review
- Review
- Combining Metformin and Drug-Loaded Kidney-Targeting Micelles for Polycystic Kidney Disease.Cellular and molecular bioengineering · 2023Article
- Nrf2 Activation in Chronic Kidney Disease: Promises and Pitfalls.Antioxidants (Basel, Switzerland) · 2022Review
- NLRP3 Inflammasome and Pyroptosis in Liver Pathophysiology: The Emerging Relevance of Nrf2 Inducers.Antioxidants (Basel, Switzerland) · 2022Review
- Antioxidant Response Activating nanoParticles (ARAPas) localize to atherosclerotic plaque and locally activate the Nrf2 pathway.Biomaterials science · 2022Article
- Alterations of hepatic gluconeogenesis and amino acid metabolism in CTRP3-deficient mice.Molecular biology reports · 2022Article
- Anti-Diabetic Potential of Plant-Based Pentacyclic Triterpene Derivatives: Progress Made to Improve Efficacy and Bioavailability.Molecules (Basel, Switzerland) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In a multinational placebo-controlled phase III clinical trial in 2,185 patients with type 2 diabetes mellitus and stage 4 chronic kidney disease, treatment with the Nrf2 activator bardoxolone methyl increased estimated glomerular filtration rate, a measure of kidney function, but also resulted in increases in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase. These increases in liver enzyme level(s) were maximal after 4 weeks of treatment and reversible, trending back toward baseline through week 48. Total bilirubin concentrations did not increase, and no cases met Hy's Law criteria, although two subjects had ALT concentrations that exceeded 10 × the upper limit of the population reference range leading to discontinuation of treatment. Animal and cell culture experiments suggested that the increases in ALT and AST induced by bardoxolone methyl may be related to its pharmacological activity. Bardoxolone methyl significantly induced the mRNA expression of ALT and AST isoforms in cultured cells. Expression of ALT and AST isoforms in liver and kidney also positively correlated with Nrf2 status in mice. Overall, these data suggest that the increases in ALT and AST observed clinically were, at least in part, related to the pharmacological induction of aminotransferases via Nrf2 activation, rather than to any intrinsic form of hepatotoxicity.
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