Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state

Joharapurkar, Amit; Patel, Vishal; Kshirsagar, Samadhan; Patel, Madhabhai M.; Savsani, Hardikkumar; Kajavadara, Chetan; Valani, Darshan; Jain, Mukul

doi:10.1016/j.crphar.2022.100102

Cited by 12 publications

(4 citation statements)

References 47 publications

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“…Individuals with kidney disease retain the ability to generate EPO, and desidustat, categorized as an oral HIF-PHI, triggers the production of endogenous EPO, maintaining levels within or close to the physiological range and resulting in an elevation of Hb levels. It is less immunogenic than rHuEPO and avoids stimulating the subcutaneous immune system [ 10 , 18 ]. Desidustat, possessing an utterly distinct chemical composition from rHuEPO, induces endogenous EPO at considerably lower peaks than conventional rHuEPO [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is less immunogenic than rHuEPO and avoids stimulating the subcutaneous immune system [ 10 , 18 ]. Desidustat, possessing an utterly distinct chemical composition from rHuEPO, induces endogenous EPO at considerably lower peaks than conventional rHuEPO [ 10 ]. In our patient, treatment with desidustat was successful, increasing and maintaining the patient's Hb levels.…”

Section: Discussionmentioning

confidence: 99%

“…This case report highlights an instance of PRCA secondary to epoetin in an elderly female and outlines its treatment with besidustat, an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor (HIF-PHI). Desidustat has demonstrated efficacy against EPO-induced PRCA by regulating EPO expression and promoting erythropoiesis [ 10 ]. The article underscores the importance of early diagnosis and treatment of PRCA in this elderly female patient, likely representing the first case in India to demonstrate the efficacy of desidustat and its benefits over EPO.…”

Section: Introductionmentioning

confidence: 99%

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A Case of Erythropoietin (EPO)-Induced Pure Red Cell Aplasia and Its Treatment Efficacy With Desidustat

Kashiv,

Malde,

Dubey

et al. 2024

Cureus

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Pure red cell aplasia (PRCA), a rare hematological disorder marked by severe anemia and reticulocytopenia, results from the near absence of developing erythroid precursors in the otherwise normal bone marrow. This case report focuses on a 48-year-old female with chronic kidney disease (CKD) who received erythropoietin injections for CKD-related secondary anemia. Despite an initial positive response, a sudden drop in hemoglobin levels prompted investigations, revealing endogenous erythropoietin (EPO)-induced PRCA due to anti-EPO antibodies. In response, desidustat, an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor, was successfully introduced as an alternative treatment. This led to a substantial and sustained improvement in hemoglobin levels, emphasizing the crucial role of swift diagnosis and intervention in EPO-induced PRCA cases. Administration method and storage conditions are noteworthy factors influencing recombinant human erythropoietin (rHuEPO) immunogenicity. The case underscores desidustat's emergence as a less immunogenic and effective alternative for anemia, marking a significant advancement, particularly in the context of this pioneering case in India showcasing its efficacy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Case of Erythropoietin (EPO)-Induced Pure Red Cell Aplasia and Its Treatment Efficacy With Desidustat

Kashiv,

Malde,

Dubey

et al. 2024

Cureus

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“…Effective utilization of iron is vital for erythropoiesis in addition to EPO release. Ineffective iron utilization leads to EPO resistance despite using higher doses of EPO [21]. Hepcidin is the protein that regulates the availability of iron in the circulation by limiting release from the liver, macrophage and other iron-storing tissue and decreasing iron absorption.…”

Section: Hifs and Phdsmentioning

confidence: 99%

The Perspective of Using Flow Cytometry for Unpuzzling Hypoxia-Inducible Factors Signalling

Patel,

Joharapurkar,

Jain

2024

Drug Res (Stuttg)

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Hypoxia-inducible factors (HIFs) are transcription factors that are responsible for adapting to the changes in oxygen levels in the cellular environment. HIF activity determines the expression of cellular proteins that control the development and physiology of the cells and pathophysiology of a disease. Understanding the role of specific HIF (HIF-1-3) in cellular function is essential for development of the HIF-targeted therapies. In this review, we have discussed the use of flow cytometry in analysing HIF function in cells. Proper understanding of HIF-signalling will help to design pharmacological interventions HIF-mediated therapy. We have discussed the role of HIF-signalling in various diseases such as cancer, renal and liver diseases, ulcerative colitis, arthritis, diabetes and diabetic complications, psoriasis, and wound healing. We have also discussed protocols that help to decipher the role of HIFs in these diseases that would eventually help to design promising therapies.

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Inhibition of alternative complement system and prolyl hydroxylase ameliorates anaemia of inflammation

Patel,

Joharapurkar,

Kshirsagar

et al. 2024

Inflammopharmacol

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Prolyl hydroxylase inhibitor desidustat improves anemia in erythropoietin hyporesponsive state

Cited by 12 publications

References 47 publications

A Case of Erythropoietin (EPO)-Induced Pure Red Cell Aplasia and Its Treatment Efficacy With Desidustat

A Case of Erythropoietin (EPO)-Induced Pure Red Cell Aplasia and Its Treatment Efficacy With Desidustat

The Perspective of Using Flow Cytometry for Unpuzzling Hypoxia-Inducible Factors Signalling

Inhibition of alternative complement system and prolyl hydroxylase ameliorates anaemia of inflammation

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