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Journal articles on the topic 'HIF-PHI'

Author: Grafiati

Published: 2 June 2025

Last updated: 31 July 2025

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1

Takahashi, Akira. "Zinc Supplementation Enhances the Hematopoietic Activity of Erythropoiesis-Stimulating Agents but Not Hypoxia-Inducible Factor–Prolyl Hydroxylase Inhibitors." Nutrients 16, no. 4 (2024): 520. http://dx.doi.org/10.3390/nu16040520.

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Since zinc is involved in many aspects of the hematopoietic process, zinc supplementation can reduce erythropoiesis-stimulating agents (ESAs) in patients undergoing hemodialysis. However, it remains unclear whether hypoxia-inducible factor–prolyl hydroxylase inhibitors (HIF-PHIs) have similar reduction effects. HIF-PHI stabilizes HIF, which promotes hematopoiesis, although HIF-1α levels are downregulated by zinc. This study aimed to investigate the effect of zinc supplementation on the hematopoietic effect of HIF-PHI in patients undergoing hemodialysis. Thirty patients undergoing maintenance h

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Yoshida, Yukina, Tomoaki Takata, Sosuke Taniguchi, et al. "Efficacy of Hypoxia-Inducible Factor Prolyl-Hydroxylase Inhibitors in Renal Anemia: Enhancing Erythropoiesis and Long-Term Outcomes in Patients with Chronic Kidney Disease." Biomedicines 12, no. 12 (2024): 2926. https://doi.org/10.3390/biomedicines12122926.

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Background/Objectives: Renal anemia is one of the major complications associated with chronic kidney disease (CKD). Erythropoietin-stimulating agents (ESAs) are commonly used; however, some patients exhibit resistance. Hypoxia-inducible factor prolyl-hydroxylase inhibitors (HIF-PHIs) have emerged as a novel treatment for renal anemia, enhancing erythropoiesis and iron metabolism. Methods: We retrospectively analyzed laboratory data related to erythropoiesis from 105 patients with CKD before and after treatment with HIF-PHI or ESA. The dialysis initiation and mortality rates were also assessed

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Koukourakis, M. I., A. Giatromanolaki, E. Sivridis, et al. "Intratumoral lactate dehydrogenase 5 (LDH5) protein expression is associated with expression of angiogenesis markers and hypoxia in patients with colorectal cancer (CRC)." Journal of Clinical Oncology 25, no. 18_suppl (2007): 4107. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.4107.

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4107 Background: Recent clinical trials (CONFIRM 1 and CONFIRM 2) have shown that metastatic CRC patients (pts) with high serum lactate dehydrogenase (LDH) derive the greatest therapeutic benefit from PTK787/ZK 222584 (PTK/ZK). PTK/ZK is a novel, oral tyrosine kinase inhibitor (TKI), which blocks all known VEGF receptors (VEGFR). From previous studies, total LDH and isoenzyme LDH5 have been associated with tumor aggressiveness and hypoxia. In the present study, we tested whether CRC pts with high levels of tumor LDH5 have increased expression of proteins involved with hypoxia (hypoxia inducibl

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Schröppel, Bernd. "HIF-PH-Inhibitoren in der Therapie der renalen Anämie." Dialyse aktuell 26, no. 10 (2022): 453–59. http://dx.doi.org/10.1055/a-1924-3492.

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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 aktiviere

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Cabral Filho, Lauro Wilson Lima Ferro, Wendell de Jesus Nunes Barbosa, Patrícia Uchõa Leitão Cabral, and Yúla Pires da Silveira Fontenele de Meneses. "Inibidores da enzima prolil hidroxilase induzida por hipóxia na saúde e no desempenho desportivo." Lecturas: Educación Física y Deportes 26, no. 277 (2021): 190–201. http://dx.doi.org/10.46642/efd.v26i277.2465.

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Os inibidores da enzima prolil hidroxilase induzida por hipóxia (HIF-PHI) é um agente terapêutico sob uma nova classe de fármacos que estimulam a resposta do corpo à hipóxia sem alterar a pressão parcial de oxigênio nos tecidos, o que suprime e induz os genes responsáveis ao processo hematopoiético. Esses agentes estimulantes de eritropoiese podem influenciar a saúde humana possibilitando novas oportunidades no tratamento de anemia com doença renal crônica, no entanto, os mesmos têm também chamando a atenção de atletas que buscam a melhoria da performance. O objetivo deste estudo foi descrever

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Hara, Ryujiro, Toshihiko Kitahara, Hiroki Numata, et al. "Daprodustat, a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor, Improves Hematological Insufficiency without Progression of Myelodysplastic Syndrome with Chronic Kidney Disease." Blood 142, Supplement 1 (2023): 6495. http://dx.doi.org/10.1182/blood-2023-182991.

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Introduction Hematological insufficiency is a critical issue in the treatment of myelodysplastic syndrome (MDS). The current standard treatment for cytopenia in MDS involves blood transfusion and the administration of erythropoiesis stimulating agents (ESAs). However, ESAs are only effective in certain patients with low erythropoietin levels; patients who are not suitable candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT) require lifelong blood transfusions. As a result, there is a growing demand for new treatments for cytopenia in MDS, and researchers have been expl

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Qian, Fang-Yuan, Zuo-Lin Li, Yu-Dong Guo, et al. "Hypoxia-inducible factor-prolyl hydroxylase inhibitor ameliorates myopathy in a mouse model of chronic kidney disease." American Journal of Physiology-Renal Physiology 317, no. 5 (2019): F1265—F1273. http://dx.doi.org/10.1152/ajprenal.00260.2019.

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Muscle wasting and diminished physical performance contribute to the morbidity and mortality of chronic kidney disease (CKD), for which no curative therapy exists. Accumulating evidence indicates that impaired angiogenesis occurs in the muscles of CKD models. Therefore, proangiogenesis therapy is considered a potentially effective strategy for limiting CKD-associated myopathy. Hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF and enhances muscle angiogenesis during acute ischemia; however, little evidence was available from CKD models. Here, we assessed wheth

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Shimoda, Larissa A., Michele Fallon, Sarah Pisarcik, Jian Wang, and Gregg L. Semenza. "HIF-1 regulates hypoxic induction of NHE1 expression and alkalinization of intracellular pH in pulmonary arterial myocytes." American Journal of Physiology-Lung Cellular and Molecular Physiology 291, no. 5 (2006): L941—L949. http://dx.doi.org/10.1152/ajplung.00528.2005.

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Vascular remodeling resulting from altered pulmonary arterial smooth muscle cell (PASMC) growth is a contributing factor to the pathogenesis of hypoxic pulmonary hypertension. PASMC growth requires an alkaline shift in intracellular pH (pHi) and we previously showed that PASMCs isolated from mice exposed to chronic hypoxia exhibited increased Na+/H+ exchanger (NHE) expression and activity, which resulted in increased pHi. However, the mechanism by which hypoxia caused these changes was unknown. In this study we tested the hypothesis that hypoxia-induced changes in PASMC pH homeostasis are medi

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Wu, Henry H. L., Rajkumar Chinnadurai, and Robert J. Walker. "Is HIF-PHI the Answer to Tackle ESA Hyporesponsiveness in the Elderly?" Kidney and Dialysis 2, no. 3 (2022): 446–53. http://dx.doi.org/10.3390/kidneydial2030040.

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Anemia in chronic kidney disease (CKD) has become an important clinical issue with the increased prevalence of elderly patients living with CKD progressing to kidney failure. The causes of anemia in elderly individuals tend to be multifactorial, exacerbated by the physiological effects of aging, frailty and declining kidney function. Erythropoiesis-stimulating agents (ESAs) are the conventional therapeutic option for anemia in CKD. However, ESA hyporesponsiveness is a commonly observed issue in clinical practice and an issue that is more challenging to resolve in elderly patients living with f

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Ogawa, Chie, Ken Tsuchiya, and Kunimi Maeda. "Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors and Iron Metabolism." International Journal of Molecular Sciences 24, no. 3 (2023): 3037. http://dx.doi.org/10.3390/ijms24033037.

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The production of erythropoietin (EPO), the main regulator of erythroid differentiation, is regulated by hypoxia-inducible factor (HIF). HIF2α seems to be the principal regulator of EPO transcription, but HIF1α and 3α also may have additional influences on erythroid maturation. HIF is also involved in the regulation of iron, an essential component in erythropoiesis. Iron is essential for the organism but is also highly toxic, so its absorption and retention are strictly controlled. HIF also induces the synthesis of proteins involved in iron regulation, thereby ensuring the availability of iron

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Watanabe, Kimio, Emiko Sato, Eikan Mishima, et al. "Changes in Metabolomic Profiles Induced by Switching from an Erythropoiesis-Stimulating Agent to a Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor in Hemodialysis Patients: A Pilot Study." International Journal of Molecular Sciences 24, no. 16 (2023): 12752. http://dx.doi.org/10.3390/ijms241612752.

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Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are a new class of medications for managing renal anemia in patients with chronic kidney disease (CKD). In addition to their erythropoietic activity, HIF-PHIs exhibit multifaceted effects on iron and glucose metabolism, mitochondrial metabolism, and angiogenesis through the regulation of a wide range of HIF-responsive gene expressions. However, the systemic biological effects of HIF-PHIs in CKD patients have not been fully explored. In this prospective, single-center study, we comprehensively investigated changes in plasma metab

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Sridharan, Vijayalakshmi, Jason Guichard, Chuan-Yuan Li, Robin Muise-Helmericks, Craig Cano Beeson, and Gary L. Wright. "O2-sensing signal cascade: clamping of O2 respiration, reduced ATP utilization, and inducible fumarate respiration." American Journal of Physiology-Cell Physiology 295, no. 1 (2008): C29—C37. http://dx.doi.org/10.1152/ajpcell.00466.2007.

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These studies explore the consequences of activating the prolyl hydroxylase (PHD) O2-sensing pathway in spontaneously twitching neonatal cardiomyocytes. Full activation of the PHD pathway was achieved using the broad-spectrum PHD inhibitor (PHI) dimethyloxaloylglycine (DMOG). PHI treatment of cardiomyocytes caused an 85% decrease in O2 consumption and a 300% increase in lactic acid production under basal conditions. This indicates a ∼75% decrease in ATP turnover rate, inasmuch as the increased ATP generation by glycolysis is inadequate to compensate for the lower respiration. To determine the

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Signore, Pierre E., Guangjie Guo, Zhihua Wei, Weihua Zhang, Al Lin, and Ughetta del Balzo. "A small-molecule inhibitor of hypoxia-inducible factor prolyl hydroxylase improves obesity, nephropathy and cardiomyopathy in obese ZSF1 rats." PLOS ONE 16, no. 8 (2021): e0255022. http://dx.doi.org/10.1371/journal.pone.0255022.

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Prolyl hydroxylase (PH) enzymes control the degradation of hypoxia-inducible factor (HIF), a transcription factor known to regulate erythropoiesis, angiogenesis, glucose metabolism, cell proliferation, and apoptosis. HIF-PH inhibitors (HIF-PHIs) correct anemia in patients with renal disease and in animal models of anemia and kidney disease. However, the effects of HIF-PHIs on comorbidities associated with kidney disease remain largely unknown. We evaluated the effects of the HIF-PHI FG-2216 in obese ZSF1 (Ob-ZSF1) rats, an established model of kidney failure with metabolic syndrome. Following

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Jordán-Fiallos, Diana Lorena, Daniela Rafaela Palacios-Córdova, Mey Anais Vuele-Cuenca, and Dariela Scarleth Seme-Albán. "HIF-PHI versus EPO con hierro en anemia de insuficiencia renal crónica [HIF-PHI versus EPO with iron in chronic renal failure anaemia]." Sanitas. Revista arbitrada de ciencias de la salud 4, especial2 (2025): 11–19. https://doi.org/10.62574/fgrek111.

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Objetivo: comparar la eficacia y seguridad de los HIF-PHI versus eritropoyetina con hierro en el tratamiento de la anemia en pacientes con insuficiencia renal crónica. Método: revisión sistemática en 16 trabajos. Resultados y Conclusión: Si bien ambos enfoques muestran efectividad similar en la elevación de los valores de hemoglobina, los HIF-PHI brindan beneficios particulares al generar una respuesta eritropoyética más natural y estable, mejorar el aprovechamiento del hierro corporal a través de la regulación de la hepcidina, y favorecer el cumplimiento del tratamiento mediante su presentaci

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Sona, Toji*1 Anu Benedict1 Ashna Saju1 Maria George2 Lincy George3. "Hif-Phi for Management of Anaemia of Chronic Kidney Disease: An Overview." International Journal of Pharmaceutical Sciences 3, no. 5 (2025): 3588–97. https://doi.org/10.5281/zenodo.15479991.

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Anaemia is a common consequence of chronic renal disease, which affects 10% of the global population. The primary cause of it is the kidneys' diminished capacity to produce enough EPO in response to hypoxia or anemia. The management of anemia and quality of life have improved with the use of ESAs and iron therapy in current treatment. This treatment raises safety concerns as it attempts to bring the hemoglobin level close to normal. HIF-PHIs, or hypoxia-inducible factor (HIF) prolyl hydroxylase domain (PHD) inhibitors, were created as a substitute method and oral treatment for anemia in chroni

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Abraham, Abi, Alan Almeida, Anil Kumar Bhalla, et al. "Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors for Treatment of Anemia in Chronic Kidney Disease: Guidelines for South Asia." Indian Journal of Nephrology 35 (February 25, 2025): 129–67. https://doi.org/10.25259/ijn_389_23.

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This guideline addresses the use of hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) in patients >18 years with chronic kidney disease (CKD) and anemia in South Asia (Bangladesh, Bhutan, Nepal, India, Pakistan, Sri Lanka). It also summarizes recommendations for anemia treatment for individual HIF-PHI molecules under two categories: dialysis-dependent and non-dialysis-dependent CKD patients. The recommendations do not apply to pediatric (≤12 years) and adolescent (12 to 18) patients or those with primary anemia or anemia secondary to other causes such as blood loss, cancer (

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Zaruba, Marc-Michael, Simon Staggl, Santhosh Kumar Ghadge, et al. "Roxadustat Attenuates Adverse Remodeling Following Myocardial Infarction in Mice." Cells 13, no. 13 (2024): 1074. http://dx.doi.org/10.3390/cells13131074.

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Activation of the CXCL12/CXCR4/ACKR3 axis is known to aid myocardial repair through ischemia-triggered hypoxia-inducible factor-1α (HIF-1α). To enhance the upregulation of HIF-1α, we administered roxadustat, a novel prolyl hydroxylase inhibitor (PHI) clinically approved by the European Medicines Agency 2021 for the treatment of renal anemia, with the purpose of improving LV function and attenuating ischemic cardiomyopathy. Methods: We evaluated roxadustat’s impact on HIF-1 stimulation, cardiac remodeling, and function after MI. Therefore, we analyzed nuclear HIF-1 expression, the mRNA and prot

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Hsieh, Matthew M., N. Seth Linde, Aisha Wynter, et al. "HIF–prolyl hydroxylase inhibition results in endogenous erythropoietin induction, erythrocytosis, and modest fetal hemoglobin expression in rhesus macaques." Blood 110, no. 6 (2007): 2140–47. http://dx.doi.org/10.1182/blood-2007-02-073254.

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Abstract The hypoxia-inducible factor (HIF) pathway is crucial in mitigating the deleterious effects of oxygen deprivation. HIF-α is an essential component of the oxygen-sensing mechanisms and under normoxic conditions is targeted for degradation via hydroxylation by HIF–prolyl hydroxylases. Several HIF–prolyl hydroxylase inhibitors (PHIs) induced erythropoietin (epo) expression in vitro and in mice, with peak epo expression ranging from 5.6- to 207-fold above control animals. Furthermore, several PHIs induced fetal hemoglobin (HbF) expression in primary human erythroid cells in vitro, as dete

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Gáll, Tamás, Dávid Pethő, Annamária Nagy, Szilárd Póliska, György Balla, and József Balla. "Prolyl Hydroxylase Inhibitor-Mediated HIF Activation Drives Transcriptional Reprogramming in Retinal Pigment Epithelium: Relevance to Chronic Kidney Disease." Cells 14, no. 14 (2025): 1121. https://doi.org/10.3390/cells14141121.

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Chronic kidney disease (CKD)-associated anemia is a global health concern and is linked to vascular and ocular complications. Hypoxia-inducible factor (HIF) stabilizers, or HIF prolyl hydroxylase inhibitors (PHIs), are promising candidates for the treatment of CKD-associated anemia. Since hypoxia and angiogenesis are involved in eye diseases, this study examined the effects of HIF-PHIs on metabolism and gene expression in retinal pigment epithelium (RPE) cells. Results revealed that PHIs differentially induced angiogenic (VEGFA, ANG) and glycolytic (PDK1, GLUT1) gene expression, with Roxadusta

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Strowitzki, Moritz, Eoin Cummins, and Cormac Taylor. "Protein Hydroxylation by Hypoxia-Inducible Factor (HIF) Hydroxylases: Unique or Ubiquitous?" Cells 8, no. 5 (2019): 384. http://dx.doi.org/10.3390/cells8050384.

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All metazoans that utilize molecular oxygen (O2) for metabolic purposes have the capacity to adapt to hypoxia, the condition that arises when O2 demand exceeds supply. This is mediated through activation of the hypoxia-inducible factor (HIF) pathway. At physiological oxygen levels (normoxia), HIF-prolyl hydroxylases (PHDs) hydroxylate proline residues on HIF-α subunits leading to their destabilization by promoting ubiquitination by the von-Hippel Lindau (VHL) ubiquitin ligase and subsequent proteasomal degradation. HIF-α transactivation is also repressed in an O2-dependent way due to asparagin

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Qian, Lingling, Xiao-qin Chen, Deyang Kong та ін. "MK8617 inhibits M1 macrophage polarization and inflammation via the HIF-1α/GYS1/UDPG/P2Y₁₄ pathway". PeerJ 11 (30 червня 2023): e15591. http://dx.doi.org/10.7717/peerj.15591.

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Background Nonresolving inflammation is a major driver of disease and needs to be taken seriously. Hypoxia-inducible factor (HIF) is closely associated with inflammation. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), as stabilizers of HIF, have recently been reported to have the ability to block inflammation. We used MK8617, a novel HIF-PHI, to study its effect on macrophage inflammation and to explore its possible mechanisms. Methods Cell viability after MK8617 and lipopolysaccharide (LPS) addition was assessed by Cell Counting Kit-8 (CCK8) to find the appropriate drug co

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Noonan, Megan L., Pu Ni, Rafiou Agoro, Elizabeth A. Swallow, Matthew R. Allen, and Kenneth E. White. "HIF-PHI Improves Anemia and Controls Circulating FGF-23 in a CKD Model." Journal of the American Society of Nephrology 31, no. 10S (2020): 146. http://dx.doi.org/10.1681/asn.20203110s1146c.

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Aoyama, Y., M. Saito, R. Sagehashi, et al. "Efficacy and safety of HIF-PHI for posttransplant anemia in kidney transplant recipients." European Urology 83 (February 2023): S575. http://dx.doi.org/10.1016/s0302-2838(23)00448-7.

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Noonan, Megan L., Pu Ni, Emmanuel Solis, et al. "HIF-PHI Have Direct Actions in Osteocytes: Implications for Anemia Treatment in CKD." Journal of the American Society of Nephrology 32, no. 10S (2021): 4. http://dx.doi.org/10.1681/asn.20213210s14b.

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Tyagi, Jyoti, Manveen Kaur, Sandeep Moola, et al. "Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors for Anemia in Non-Dialysis Dependent Chronic Kidney Disease: Systematic Review and Meta-Analysis of Randomized Controlled Trials." Indian Journal of Nephrology 35 (February 25, 2025): 217–33. https://doi.org/10.25259/ijn_382_23.

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Background Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) is a new therapy option for anemia in chronic kidney disease (CKD) patients. We aimed to evaluate evidence from randomized controlled trials (RCTs) on HIF-PHIs for anemia in non-dialysis dependent (NDD)-CKD patients. Materials and Methods We searched three electronic databases (PubMed, CINAHL, Cochrane Central Register of Controlled Trials databases), trial registries, and manually screened reference list. Two authors independently conducted screening, data extraction, and assessed risk of bias. We used RevMan 5.3 for

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Shah, Shivam Narendrakumar, Himanshu Patel, Vivek Kute, et al. "Rhabdomyolysis and Neuroleptic Malignant Syndrome in a Postrenal Transplant Patient: Is Desidustat a Culprit?" Indian Journal of Transplantation 18, no. 2 (2024): 174–76. http://dx.doi.org/10.4103/ijot.ijot_63_23.

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We report a case of a 46-year-old female – a postrenal transplant patient, having developed rhabdomyolysis and neuroleptic malignant syndrome (NMS), after 2.5 months of desidustat initiation – for anemia. Post renal transplant anemia (PTA) is common among renal transplant recipients. Apart from treating it with iron supplements, folic acid, andrecombinant human erythropoietin (EPO), novel agents like hypoxia-inducible factor–prolyl hydroxylase domain (HIF–PHI) are also used, with a very few studies available on its efficacy and safety in PTA patients. Anemia occurring in the first 6 months is

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Takahashi, Akira. "Co-Administration of Roxadustat and Zinc Stabilizes Both Serum Copper and Zinc Concentrations in Patients Undergoing Hemodialysis." Nutrients 15, no. 23 (2023): 4887. http://dx.doi.org/10.3390/nu15234887.

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Patients undergoing hemodialysis often require zinc supplementation owing to hypozincemia, which may reduce serum copper concentrations. However, hypoxia-inducible factor–prolyl hydroxylase inhibitors (HIF-PHIs), which are used to treat renal anemia, have been reported to increase serum copper. Therefore, this study investigates the effectiveness of a combination of HIF-PHIs and zinc for the stabilization of serum copper and zinc concentrations during zinc supplementation for patients undergoing hemodialysis with renal anemia and hypozincemia. The serum zinc and copper concentrations were retr

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王, 加如. "The Mechanism of HIF-PHI in the Treatment of Renal Anemia and the Research Progress of Roxadustat." Advances in Clinical Medicine 12, no. 06 (2022): 5891–96. http://dx.doi.org/10.12677/acm.2022.126853.

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Parmar, Deven V., Kevinkumar A. Kansagra, Jatin C. Patel, et al. "Outcomes of Desidustat Treatment in People with Anemia and Chronic Kidney Disease: A Phase 2 Study." American Journal of Nephrology 49, no. 6 (2019): 470–78. http://dx.doi.org/10.1159/000500232.

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Background: Desidustat (ZYAN1) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) that stimulates erythropoiesis. Stabilizing HIF via PHI is developing as a new therapeutic approach to treat anemia secondary to chronic kidney disease (CKD). This trial evaluated the safety, tolerability, and efficacy of Desidustat in adult CKD patients with anemia, who were not on dialysis. Methods: This was a Phase 2, randomized, double-blind, 6-week, placebo-controlled, dose-ranging, safety and efficacy study. A total of 117 eligible patients were randomized to 4 arms: 100, 150, 200 mg

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Grzeszczak, Władysław, Dariusz Szczyra, and Mirosław Śnit. "Whether Prolyl Hydroxylase Blocker—Roxadustat—In the Treatment of Anemia in Patients with Chronic Kidney Disease Is the Future?" International Journal of Environmental Research and Public Health 18, no. 4 (2021): 1612. http://dx.doi.org/10.3390/ijerph18041612.

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In patients with chronic kidney disease (CKD), anemia develops gradually, which is primarily due to an inadequate synthesis of erythropoietin by the kidneys, as well as to iron disorders in the body, blood loss, shortened erythrocyte survival and inflammation. The currently accepted treatment employs iron, vitamin B12, folic acid supplementation and the use of erythropoiesis stimulants, which are administered only parenterally. Research is currently underway on the new erythropoiesis drugs that can be orally administered, i.e., hypoxia-inducible factor-propyl hydroxylase inhibitor (HIF-PHI) in

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Nguyen, Timothy. "Daprodustat—An HIF-PHI Inhibitor: The First Oral Medication for the Treatment of Anemia in Dialysis." Journal for Nurse Practitioners 19, no. 7 (2023): 104645. http://dx.doi.org/10.1016/j.nurpra.2023.104645.

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Kapitsinou, PP, G. Rajendran, L. Astleford, et al. "ID: 113: THE ENDOTHELIAL PHD2/HIF-2 AXIS REGULATES PULMONARY ARTERY PRESSURE IN MICE." Journal of Investigative Medicine 64, no. 4 (2016): 961.2–962. http://dx.doi.org/10.1136/jim-2016-000120.103.

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BackgroundPulmonary hypertension (PH), a common clinical problem characterized by increased pulmonary artery (PA) pressure, is frequently triggered by hypoxia. Key mediators of cellular hypoxia responses are hypoxia-inducible factors (HIF)-1 and -2, the activity of which is regulated by prolyl-4-hydroxylase domain (PHD) proteins, with PHD2 being the main oxygen sensor that controls HIF activity under normoxia. Although both transcription factors are expressed in the lung, little is known about their cell type-specific roles in the pathogenesis of PH.Methods and ResultsHere we used a genetic ap

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CG, Sreedhar, Athish M N, Kishan A, et al. "WCN25-4053 A CASE SERIES OF POST TRANSPLANT - PARVOVIRUS B19 INDUCED ANAEMIA TREATED WITH NOVEL HIF-PHI: DESIDUSTAT." Kidney International Reports 10, no. 2 (2025): S546—S547. https://doi.org/10.1016/j.ekir.2024.11.978.

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Provenzano, R., G. Fadda, M. Bernardo, et al. "212: FG2216, A Novel Oral HIF-PHI, Stimulates Erythropoiesis and Increases Hemoglobin Concentration in Patients with Non-Dialysis CKD." American Journal of Kidney Diseases 51, no. 4 (2008): B80. http://dx.doi.org/10.1053/j.ajkd.2008.02.222.

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Del Vecchio, Lucia, and Francesco Locatelli. "Investigational hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI) for the treatment of anemia associated with chronic kidney disease." Expert Opinion on Investigational Drugs 27, no. 7 (2018): 613–21. http://dx.doi.org/10.1080/13543784.2018.1493455.

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Bhatia, Rajeev Kumar, Ajay Marwaha, Basant Pawar, et al. "WCN25-2264 ONE-YEAR RETROSPECTIVE ANALYSIS OF DESIDUSTAT: A PROMISING HIF-PHI FOR ANEMIA MANAGEMENT IN DIALYSIS-DEPENDENT CKD PATIENTS." Kidney International Reports 10, no. 2 (2025): S106. https://doi.org/10.1016/j.ekir.2024.11.250.

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Sinha, Vijay, Amit Devra, and Ravi SIngh. "WCN25-2356 REAL WORLD EXPERIENCE OF HIF-PHI – DESIDUSTAT (OXEMIA®) IN DIALYSIS AND NON-DIALYSIS DEPENDENT CKD ANEMIA PATIENTS." Kidney International Reports 10, no. 2 (2025): S108. https://doi.org/10.1016/j.ekir.2024.11.254.

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Agarwal, Rajiv, Dennis Vargo, Wenli Luo, Christine Solinsky, and Glenn M. Chertow. "Vadadustat, an Oral HIF-PHI, Is Not Associated with Increased Risk of Neoplasm in Patients with Anemia due to CKD." Journal of the American Society of Nephrology 32, no. 10S (2021): 183–84. http://dx.doi.org/10.1681/asn.20213210s1183d.

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Badura, Krzysztof, Jędrzej Janc, Joanna Wąsik, et al. "Anemia of Chronic Kidney Disease—A Narrative Review of Its Pathophysiology, Diagnosis, and Management." Biomedicines 12, no. 6 (2024): 1191. http://dx.doi.org/10.3390/biomedicines12061191.

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Anemia is one of the most common chronic kidney disease (CKD) complications. It negatively affects patients’ quality of life and clinical outcomes. The pathophysiology of anemia in CKD involves the interplay of various factors such as erythropoietin (EPO) deficiency, iron dysregulation, chronic inflammation, bone marrow dysfunction, and nutritional deficiencies. Despite recent advances in understanding this condition, anemia still remains a serious clinical challenge in population of patients with CKD. Several guidelines have been published with the aim to systematize the diagnostic approach a

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Singh, Indrajeet, Wojciech Krzyzanski, and Pratap Singh. "A Mechanism Based Pharmacokinetic/Pharmacodynamic Model of the Effect of a Prolyl Hydroxylase Inhibitor on Erythropoietic Response In Mice." Blood 116, no. 21 (2010): 4769. http://dx.doi.org/10.1182/blood.v116.21.4769.4769.

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Abstract Abstract 4769 Background: The oxygen sensing pathway is one of the major controlling mechanisms of erythropoiesis in humans and other mammals. The transcription factor, Hypoxia-Inducible-Factor (HIF) regulates the local gene expression of the hormone erythropoietin (EPO). Degradation of HIF1α is regulated via oxygen dependent pathway by Prolyl Hydroxylases (PHDs) enzymes and the inhibition of PHD enzyme activity stimulates the erythropoietic response. The purpose of this study was to develop a mechanistic Pharmacokinetic/Pharmacodynamic (PK/PD) model to describe the effect of a Prolyl

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Noonan, Megan L., Pu Ni, Rafiou Agoro, et al. "The HIF‐PHI BAY 85‐3934 (Molidustat) Improves Anemia and Is Associated With Reduced Levels of Circulating FGF23 in a CKD Mouse Model." Journal of Bone and Mineral Research 36, no. 6 (2021): 1117–30. http://dx.doi.org/10.1002/jbmr.4272.

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Ogawa, Chie, Ken Tsuchiya, and Kunimi Maeda. "Validate Optimal Iron Management When Using Hypoxia-Inducible Factor-Prolyl Hydroxylase Domain Inhibitor (HIF-PHI) in Renal Anemia: Excessive Iron Administration Is Unnecessary." Journal of the American Society of Nephrology 34, no. 11S (2023): 363. http://dx.doi.org/10.1681/asn.20233411s1363c.

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Flinck, Mette, Sofie Hagelund, Andrej Gorbatenko та ін. "The Vacuolar H+ ATPase α3 Subunit Negatively Regulates Migration and Invasion of Human Pancreatic Ductal Adenocarcinoma Cells". Cells 9, № 2 (2020): 465. http://dx.doi.org/10.3390/cells9020465.

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Increased metabolic acid production and upregulation of net acid extrusion render pH homeostasis profoundly dysregulated in many cancers. Plasma membrane activity of vacuolar H+ ATPases (V-ATPases) has been implicated in acid extrusion and invasiveness of some cancers, yet often on the basis of unspecific inhibitors. Serving as a membrane anchor directing V-ATPase localization, the a subunit of the V0 domain of the V-ATPase (ATP6V0a1-4) is particularly interesting in this regard. Here, we map the regulation and roles of ATP6V0a3 in migration, invasion, and growth in pancreatic ductal adenocarc

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Kumari, Reena, Senthilnathan Palaniyandi, Ethan Strattan, Sabarinath Venniyil Radhakrishnan, and Gerhard Carl Hildebrandt. "Dimethyl Oxalyl Glycine a Prolyl Hydroxylase Inhibitor Decreases Early Gastrointestinal Gvhd Via Two Independent Pathways of Apoptosis after Allogeneic Hematopoietic Cell Transplantation." Blood 132, Supplement 1 (2018): 3317. http://dx.doi.org/10.1182/blood-2018-99-116245.

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Abstract Introduction: Allogeneic hematopoietic cell transplantation (HCT) is increasingly utilized in the treatment of hematologic malignant and non-malignant diseases. Therapy-related toxicity and graft versus host disease (GVHD) remain major challenges as they significantly contribute to treatment related morbidity and mortality. Prolyl hydroxylase inhibitors (PHI) interfere with signaling cascades of inflammation and cell death. Their beneficial use in experimental models of ulcerative colitis and lung allograft rejection resulted in the hypothesis, that use of the PHI dimethyl oxalyl glyc

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Wang, Ling, Yongwei Song, Pan Zhang, et al. "Hypoxia‐inducible factor prolyl hydroxylase inhibitor alleviates heatstroke‐induced acute kidney injury by activating BNIP3‐mediated mitophagy." FASEB Journal 38, no. 12 (2024). http://dx.doi.org/10.1096/fj.202400047r.

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AbstractHypoxia‐induced inflammation and apoptosis are important pathophysiological features of heat stroke‐induced acute kidney injury (HS‐AKI). Hypoxia‐inducible factor (HIF) is a key protein that regulates cell adaptation to hypoxia. HIF‐prolyl hydroxylase inhibitor (HIF‐PHI) stabilizes HIF to increase cell adaptation to hypoxia. Herein, we reported that HIF‐PHI pretreatment significantly improved renal function, enhanced thermotolerance, and increased the survival rate of mice in the context of HS. Moreover, HIF‐PHI could alleviate HS‐induced mitochondrial damage, inflammation, and apoptos

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Zheng, Li, Ming Liu, Yatong Zhang, Kaihua Zhang, Yanting Gu, and Deping Liu. "Bibliometric analysis of hypoxia inducible factor prolyl hydroxylase inhibitor in anemia." Frontiers in Pharmacology 13 (September 21, 2022). http://dx.doi.org/10.3389/fphar.2022.1005225.

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Objective: This study aimed to explore the global research status, hot topics, and future prospects in the field of the hypoxia inducible factor prolyl hydroxylase inhibitor (HIF-PHI) by bibliometric analysis.Methods: The literatures about HIF-PHI were downloaded from the Web of Science Core Collection and Pubmed database from inceptions to January.10th. 2022. The VOSviewer 1.6.18 was used to explore the bibliometric networks and research priorities of HIF-PHI.Results: A total of 409 papers about HIF-PHI were included, involving 1,674 authors from 548 institutions in 43 countries. The number o

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Ren, Song, Xiaoxiu Yao, Yi Li, Ying Zhang, Chao Tong, and Yunlin Feng. "Efficacy and safety of hypoxia-inducible factor-prolyl hydroxylase inhibitor treatment for anemia in chronic kidney disease: an umbrella review of meta-analyses." Frontiers in Pharmacology 14 (November 30, 2023). http://dx.doi.org/10.3389/fphar.2023.1296702.

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The objective was to provide a comprehensive summary of existing evidence on the efficacy and safety of hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) for the treatment of anemia in chronic kidney disease (CKD). A systematic search was conducted in the Medline, Embase, and Cochrane databases. Only meta-analyses that evaluated the efficacy and safety of HIF-PHI treatment for anemia in CKD were included. The efficacy outcomes included hemoglobin levels and iron metabolism indices, while the safety outcomes were assessed by examining adverse events. The qualities of methodologi

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Yang, Ya-Hui, Yishakejiang Saimaiti, Yang Zhao, and Wen Tang. "Plasma phospholipids profiling changes were associated with the therapeutic response to Roxadustat in peritoneal dialysis patients." Frontiers in Physiology 14 (December 18, 2023). http://dx.doi.org/10.3389/fphys.2023.1279578.

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Background: Elevated Phospholipids (PLs) and sphingolipid (SM) metabolism relates to with poor clinical status and adverse outcome of end-stage kidney disease patients undergoing peritoneal dialysis (PD). Studies have suggested that the use of hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) (Roxadustat) is associated with altered lipid metabolism. Observing on how PLs and SMs changes after the HIF-PHI treatment in PD patients may help understand the possible effect of HIF-PHI on PD patients besides correcting of anemia.Materials and methods: Stable peritoneal dialysis (PD) pati

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"Daprodustat (Jesduvroq) for Anemia of Chronic Kidney Disease." Medical Letter on Drugs and Therapeutics 66, no. 1696 (2024): 25–27. http://dx.doi.org/10.58347/tml.2024.1696a.

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The FDA has approved daprodustat (Jesduvroq – GSK), a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), for oral treatment of anemia due to chronic kidney disease (CKD) in adults who have been on dialysis for at least 4 months. It is the first HIF-PHI and the first oral drug to be approved in the US for this indication.

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Nakamura, Hironori, Shigekazu Kurihara, Mariko Anayama, Yasushi Makino, and Masaki Nagasawa. "Four Cases of Serum Copper Excess in Patients with Renal Anemia Receiving a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor: A Possible Safety Concern." Case Reports in Nephrology and Dialysis, August 19, 2022, 124–31. http://dx.doi.org/10.1159/000525735.

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Copper is an indispensable trace metal element and is mainly absorbed in the stomach and small intestine and excreted into the bile. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) have emerged as a novel approach for renal anemia management. Many intestinal genes, including <i>divalent metal transporter 1</i>, <i>duodenal cytochrome B</i>, and copper transporter ATPase7A<i>,</i> related to iron absorption are transactivated by HlF-α, during iron deficiency. We first report 4 cases of patients with renal anemia who showed excess in serum co

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