Hypoxia-Inducible Factor Stabilizers in End Stage Kidney Disease: "Can the Promise Be Kept?"

Abstract

Anemia is a common complication of chronic kidney disease (CKD). The prevalence of anemia in CKD strongly increases as the estimated Glomerular Filtration Rate (eGFR) decreases. The pathophysiology of anemia in CKD is complex. The main causes are erythropoietin (EPO) deficiency and functional iron deficiency (FID). The administration of injectable preparations of recombinant erythropoiesis-stimulating agents (ESAs), especially epoetin and darbepoetin, coupled with oral or intravenous(iv) iron supplementation, is the current treatment for anemia in CKD for both dialysis and non-dialysis patients. This approach reduces patients' dependence on transfusion, ensuring the achievement of optimal hemoglobin target levels. However, there is still no evidence that treating anemia with ESAs can significantly reduce the risk of cardiovascular events. Meanwhile, iv iron supplementation causes an increased risk of allergic reactions, gastrointestinal side effects, infection, and cardiovascular events. Currently, there are no studies defining the best strategy for using ESAs to minimize possible risks. One class of agents under evaluation, known as prolyl hydroxylase inhibitors (PHIs), acts to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. Several randomized controlled trials showed that HIF-PHIs are almost comparable to ESAs. In the era of personalized medicine, it is possible to envisage and investigate specific contexts of the application of HIF stabilizers based on the individual risk profile and mechanism of action.

• Authors: Giuseppina Crugliano, Raffaele Serra, Nicola Ielapi, Yuri Battaglia, Giuseppe Coppolino, Davide Bolignano, Umberto Marcello Bracale, Antonio Pisani, Teresa Faga, Ashour Michael, Michele Provenzano, Michele Andreucci
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 22 (Nov 22 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34830468 (Publication Type: Journal Article, Review)

Chemical References

• Hematinics
• Prolyl-Hydroxylase Inhibitors
• Iron

Topics

• Anemia, Iron-Deficiency (diet therapy, drug therapy, pathology)
• Dialysis
• Glomerular Filtration Rate (drug effects)
• Hematinics (therapeutic use)
• Humans
• Iron (therapeutic use)
• Kidney Failure, Chronic (drug therapy, enzymology)
• Prolyl-Hydroxylase Inhibitors (therapeutic use)
• Renal Insufficiency, Chronic (drug therapy, genetics, pathology)