Antifibrotic Therapy

Strutz, Frank

doi:10.1681/asn.2013101034

Cited by 4 publications

(5 citation statements)

References 14 publications

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“…Synthetic triterpenoid bardoxolone methyl and its analogs are potent activators of the Nrf2 pathway, and clinical trials that included individuals with type 2 diabetes mellitus and stage 3b or 4 CKD demonstrated that it reduced serum creatinine concentrations for up to 52 weeks (de Zeeuw et al, 2013b ). However, a phase 3 BEACON trial was terminated because of serious side effects, including increased mortality (De Zeeuw et al, 2013a ; de Zeeuw et al, 2013b ; Strutz, 2014 ). Nonetheless, Nrf2 remains an attractive potential drug target for CKD, as shown by the approval of another Nrf2 activator, dimethyl fumarate, for multiple sclerosis.…”

Section: Nuclear Factor Erythroid-2 Related Factor 2 and Renal Fibrosmentioning

confidence: 99%

Oxidative Stress and Renal Fibrosis: Recent Insights for the Development of Novel Therapeutic Strategies

et al. 2018

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Chronic kidney disease (CKD) is a significant worldwide healthcare problem. Regardless of the initial injury, renal fibrosis is the common final pathway leading to end stage renal disease. Although the underlying mechanisms are not fully defined, evidence indicates that besides inflammation, oxidative stress plays a crucial role in the etiology of renal fibrosis. Oxidative stress results from an imbalance between the production of free radicals that are often increased by inflammation and mitochondrial dysfunction, and reduced anti-oxidant defenses. Several studies have demonstrated that oxidative stress may occur secondary to activation of transforming growth factor β1 (TGF-β1) activity, consistent with its role to increase nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) activity. A number of other oxidative stress-related signal pathways have also been identified, such as nuclear factor erythroid-2 related factor 2 (Nrf2), the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-cGMP-dependent protein kinase 1-phosphodiesterase (cGMP-cGK1-PDE) signaling pathway, and the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. Several antioxidant and renoprotective agents, including cysteamine bitartrate, epoxyeicosatrienoic acids (EETs), and cytoglobin (Cygb) have demonstrated ameliorative effects on renal fibrosis in preclinical or clinical studies. The mechanism of action of many traditional Chinese medicines used to treat renal disorders is based on their antioxidant properties, which could form the basis for new therapeutic approaches. This review focuses on the signaling pathways triggered by oxidative stress that lead to renal fibrosis and provides an update on the development of novel anti-oxidant therapies for CKD.

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Section: Nuclear Factor Erythroid-2 Related Factor 2 and Renal Fibrosmentioning

confidence: 99%

Oxidative Stress and Renal Fibrosis: Recent Insights for the Development of Novel Therapeutic Strategies

et al. 2018

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“…4 However, to date, only a few studies have examined the link between health insurance and these specific access issues on the path to ESRD. This is particularly relevant because more than two thirds of new cases are attributable to diabetes and hypertension.…”

Section: Disclosuresmentioning

confidence: 99%

“…Oxidant stress and related inflammation are well recognized profibrotic mediator mechanisms that are currently the primary focus of preclinical and clinical work that tests various drugs that are designed to reduce renal fibrosis via inhibition of these mechanisms. 4 US Food and Drug Administration-approved drugs to slow the progression of CKD to ESRD, particularly when proteinuria is present, currently include renin-angiotensin-aldosterone system inhibitors (e.g., spironolactone) and nondihydropyridine calcium channel blockers. 3,4 The renal damage seen in CKD of other etiologies is also present in DN, but it is compounded by more pronounced lesions in the tubulointerstitium and blood vessels.…”

mentioning

confidence: 99%

“…4 US Food and Drug Administration-approved drugs to slow the progression of CKD to ESRD, particularly when proteinuria is present, currently include renin-angiotensin-aldosterone system inhibitors (e.g., spironolactone) and nondihydropyridine calcium channel blockers. 3,4 The renal damage seen in CKD of other etiologies is also present in DN, but it is compounded by more pronounced lesions in the tubulointerstitium and blood vessels. 3 Modestly effective therapies in patients with diabetes who are at risk for or diagnosed with DN include glycemic and BP control, smoking cessation, weight loss, and renin-angiotensin-aldosterone system inhibition once albuminuria and CKD have developed.…”

mentioning

confidence: 99%

“…Although such agents may be ameliorating one pathophysiologic component of CKD, they may "ignore" others, and some drugs have been found to cause adverse effects, 4 as was the case with bardoxolone methyl.…”

mentioning

confidence: 99%

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