Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease

Natale, Patrizia; Palmer, Suetonia C.; Jauré, Allison; Hodson, Elisabeth M; Ruospo, Marinella; Cooper, Tess E; Hahn, Deirdré; Saglimbene, Valeria; Craig, Jonathan C.; Strippoli, Giovanni F.M.

doi:10.1002/14651858.cd013751.pub2

Cited by 10 publications

(8 citation statements)

References 103 publications

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“…HIF-α protein stabilization by PHD inhibition with roxadustat (FG-4592), a novel oral PHD inhibitor, has been claimed to increase the production of EPO and treat the anemia of CKD in clinical trials [ 163 ]. However, the first Cochrane review on this subject concluded that HIF stabilization has uncertain, if any, benefits on cardiovascular and renal outcomes in CKD patients, regardless of the presence of diabetes [ 164 ]. Experimental findings suggest that HIF-α induction by roxadustat, or the classic hypoxia mimetic cobalt chloride, can counteract diabetes-associated alterations in renal energy metabolism [ 165 ], protect against metabolic disorders and DKD [ 165 , 166 , 167 , 168 ], and prevent the progression of atherosclerosis [ 162 ].…”

Section: Dysregulated Hif Signaling and Redox Homeostasis In Cardiova...mentioning

confidence: 99%

Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes

et al. 2022

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Oxidative stress and hypoxia-inducible factors (HIFs) have been implicated in the pathogenesis of diabetic cardiovascular and renal diseases. Reactive oxygen species (ROS) mediate physiological and pathophysiological processes, being involved in the modulation of cell signaling, differentiation, and survival, but also in cyto- and genotoxic damage. As master regulators of glycolytic metabolism and oxygen homeostasis, HIFs have been largely studied for their role in cell survival in hypoxic conditions. However, in addition to hypoxia, other stimuli can regulate HIFs stability and transcriptional activity, even in normoxic conditions. Among these, a regulatory role of ROS and their byproducts on HIFs, particularly the HIF-1α isoform, has received growing attention in recent years. On the other hand, HIF-1α and HIF-2α exert mutually antagonistic effects on oxidative damage. In diabetes, redox-mediated HIF-1α deregulation contributes to the onset and progression of cardiovascular and renal complications, and recent findings suggest that deranged HIF signaling induced by hyperglycemia and other cellular stressors associated with metabolic disorders may cause mitochondrial dysfunction, oxidative stress, and inflammation. Understanding the mechanisms of mutual regulation between HIFs and redox factors and the specific contribution of the two main isoforms of HIF-α is fundamental to identify new therapeutic targets for vascular complications of diabetes.

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Section: Dysregulated Hif Signaling and Redox Homeostasis In Cardiova...mentioning

confidence: 99%

Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes

et al. 2022

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“…Dadurch besteht die Möglichkeit von unerwünschten therapiebedingten Nebenwirkungen. Zu diesen zählen unter anderem ein potenziell erhöhtes Risiko für Tumorerkrankungen, -progression, Thrombose, Herz-Kreislauf-Erkrankungen, Fortschreiten der diabetischen Retinopathie und raschere Progression von Nierenzysten bei PKD 12 , 25 . Experimentelle Studien haben jedoch gezeigt, dass HIF-PHI die gewünschten proerythropoetischen Effekte in Dosierungen erreichen, die noch keine breit angelegte HIF-Antwort zur Folge haben, unter anderem auch keine messbare VEGF-Stimulation (VEGF: „vascular endothelial growth factor“) 31 .…”

Section: Sicherheit Von Hif-phisunclassified

“…In den Zulassungsstudien der HIF-PHI wurden sowohl dialysepflichtige als auch nichtdialysepflichtige CKD-Patienten untersucht. Eine kürzlich publizierte Cochrane-Analyse hat 51 Studien mit insgesamt fast 31 000 Patienten hinsichtlich des Nutzens und möglicher Nebenwirkungen der HIF-PHI-Therapie analysiert [12].…”

Section: Klinische Studienunclassified

“…Die potenziellen Vorteile sind noch nicht kungen. Zu diesen zählen unter anderem ein potenziell erhöhtes Risiko für Tumorerkrankungen, -progression, Thrombose, Herz-Kreislauf-Erkrankungen, Fortschreiten der diabetischen Retinopathie und raschere Progression von Nierenzysten bei PKD[12,25]. Experimentelle Studien haben jedoch gezeigt, dass HIF-PHI die gewünschten proerythropoetischen Effekte in Dosierungen errei-▶Tab.…”

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HIF-PH-Inhibitoren in der Therapie der renalen Anämie

Schröppel

2022

Dialyse aktuell

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ZUSAMMENFASSUNGDie bisherige Standardbehandlung der renalen Anämie umfasst die Sicherstellung ausreichender Eisenspeicher und die Verabreichung von Erythropoetin-Stimulanzien (ESA). Eine medikamentöse Alternative zu ESA sind nun Wirkstoffe, die HIF-PH (HIF: Hypoxie induzierbarer Faktor; PH: Prolylhydroxylasen) inhibieren. Denn Prolylhydroxylasen vermitteln den sauerstoffabhängigen Abbau von HIF und regulieren so die zelluläre Antwort auf Hypoxie in der Anämie und eine Reihe anderer chronischer Erkrankungen. HIF-PH-Inibitoren (HIF-PHI) sind eine neue Klasse oraler Medikamente, die HIF aktivieren und durch mehrere Mechanismen die Erythropoese steigern. HIF-PHI erhöhen nicht nur die Produktion von Erythropoetin und optimieren den Eisenmetabolismus, sondern besitzen durch die Vielzahl an HIF-regulierten Genen weitere zielgerichtete Wirkungen. Basierend auf den Daten zur Korrektur der renalen Anämie und zur Sicherheit bei dialysepflichtigen und nichtdialysepflichtigen Patienten mit chronischer Nierenerkrankung (CKD: „chronic kidney disease“) ist diese neue Wirkstoffklasse eine Alternative zu ESA. Die Europäische Arzneimittel-Agentur (EMA) hat Roxadustat im August 2021 für die klinische Anwendung in der Europäischen Union zugelassen.

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“…A depth literature review reveals that not a single method is available for the determination of newer Desidustat antianemic agents till date [7][8][9][10][11][12][13]. So though of interest for qualitative and quantitative estimation of Desidustat in bulk and tablet dosage form by beneficial highperformance thin-layer chromatography (HPTLC) method came as it is less time-and mobile phase-consuming, costeffective, environmental pollution problem controlling…”

Section: Introduction [1-7]mentioning

confidence: 99%

A sensitive, precise, accurate, and economic planar chromatographic method developed and validated for quantification of Desidustat as per guideline

Pandya¹,

Kachhiya²,

Solanki³

et al. 2023

Separation Science Plus

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Anemia with chronic kidney disease treating newer hope is recently approved Desidustat. By following International Conference on Harmonization Quality guideline Q2 (R1), an economic high‐performance thin‐layer chromatography method has been developed for the estimation of Desidustat. Pre‐coated silica gel 60 F254 plates as stationary phase along with mobile phase toluene:methanol:glacial acetic acid (7.5:2.5:0.3 v/v/v), and 230 nm detection wavelength was selected as optimized. Developed method was found linear in quantity per band range of 100 ng/band to 600 ng/band for Desidustat with 0.9979 regression coefficient. Standard spiking method showed method accuracy with a mean percentage recovery of 99.21%–101.63%. Limit of detection and limit of quantitation were found to be 3.94 and 11.94 ng/band, respectively. The method was found to be linear, precise, accurate, robust, rugged, selective, sensitive, and specific for the quantification of Desidustat in bulk and tablet dosage form and successfully can be applied for the qualitative and quantitative determination of Desidustat in bulk and marketed tablet formulation.

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Hypoxia-inducible factor stabilisers for the anaemia of chronic kidney disease

Cited by 10 publications

References 103 publications

Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes

Mutual Regulation between Redox and Hypoxia-Inducible Factors in Cardiovascular and Renal Complications of Diabetes

HIF-PH-Inhibitoren in der Therapie der renalen Anämie

A sensitive, precise, accurate, and economic planar chromatographic method developed and validated for quantification of Desidustat as per guideline

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