The role of hypoxia-inducible factor stabilizers in the treatment of anemia in patients with chronic kidney disease

Anemia contributes to increased morbidity and mortality in chronic kidney disease patients. The pathogenesis of anemia in these patients is multifactorial, but the contribution of erythropoietin deficiency becomes greater as glomerular filtration rate declines which related to decreased nephron mass. The current standard of care includes supplemental iron, erythropoiesis-stimulating agents (ESA), and red blood cell transfusions, although each has drawbacks. Lately, concern has arisen following randomized clinical trials showing that higher hemoglobin targets and/or high ESA doses may cause significant harm including increasing cardiovascular and thrombotic events, and even death. Recent experimental and clinical studies show the promising efficacy of hypoxia inducible factor (HIF) stabilizer which stimulates endogenous erythropoietin production and enhance iron availability.

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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 ◽

10.3390/ijerph18041612 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1612

Author(s):

Władysław Grzeszczak ◽

Dariusz Szczyra ◽

Mirosław Śnit

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Phase 1 ◽

Hypoxia Inducible Factor ◽

Folic Acid Supplementation ◽

The Body ◽

Oral Drug ◽

Expression Of Genes ◽

Erythrocyte Survival

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) inhibitors which temporarily block propyl hydroxylase [PHD] catalysis and promote a transient increase in the expression of genes regulated by HIF, including kidney and liver erythropoietin [EPO]. Roxadustat is the first oral drug in this class and a potent HIF-PHD inhibitor, exerted to treat anemia in patients with CKD. In phase 1, 2 and 3 studies with CKD-affected patients, roxadustat was more effective to stimulate erythropoiesis for anemia correction than previously used drugs. Roxadustat can be orally given, unlike other erythropoiesis drugs with parenteral administration only, which grants roxadustat a considerable advantage. Our paper presents the results of studies with roxadustat applied for the treatment of anemia in CKD patients with or without dialysis. We are currently not yet able to know the exact role of roxadustat in the treatment of anemia in patients with CKD, but time will tell. It is possible that roxadustat has benefits an iron metabolism and cardiovascular risk.

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Research of the level of erythropoietin and hypoxia-inducible factor 1-alpha in the blood of children and adolescents with anemia at stage C1–5 of chronic kidney disease

Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) ◽

10.21508/1027-4065-2020-65-1-77-85 ◽

2020 ◽

Vol 65 (1) ◽

pp. 77-85

Author(s):

E. V. Leonteva ◽

N. D. Savenkova

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Therapy Group ◽

Hypoxia Inducible Factor ◽

Hypoxia Inducible Factor 1 ◽

Group 3 ◽

Group 2 ◽

Erythropoietin Stimulating Agents ◽

Group 1

Purpose. To examine the indicators of iron deficiency, the levels of hemoglobin, erythropoietin, hypoxia-induced factor 1-alpha (HIF-1α) in the blood of children with anemia and chronic kidney disease C1-5 prior to the dialysis and on its background, receiving and not receiving iron preparations and erythropoietin-stimulating drugs to establish the role of HIF-1α in the regulation of erythropoietin synthesis and erythropoiesis. Results. The patients (n=80) with anemia and chronic kidney disease were divided into 3 groups: Group 1: 32 patients with chronic kidney disease C1-5 prior to the dialysis, not receiving therapy; Group 2: 18 patients with chronic kidney disease C2-5 prior to the dialysis, receiving iron-containing preparations and erythropoietin-stimulating drugs; Group 3: 30 patients with chronic kidney disease C3-5 on dialysis, receiving iron preparations and erythropoietin-stimulating drugs. Group 1: we found the increased levels of erythropoietin (28.65 ± 3.66 MIU/ml) and HIF-1α (0.089 ± 0.011 ng/ml; p=0.014 and p=0.005, respectively); Group 2: 63.01 ± 14.84 mIU/ml and 0.138 ± 0.025 ng/ml; p=0.0088 and p=0.005, respectively). Group 3: we found the increased level of HIF-1α (0.098 ± 0.01 ng/ml; p=0.005).Conclusion. An increase in concentration of HIF-1α in children with anemia and chronic kidney disease C1-5 prior and on dialysis receiving and not receiving therapy with iron-containing drugs and erythropoietin-stimulating agents confirms the role of HIF-1α in the regulation of erythropoietin and erythropoiesis synthesis in anemia.

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Potential effect of pharmaceutical care to improve outcomes in patients with chronic kidney disease-mineral bone disorder in Sulaimani dialysis centers

Al Mustansiriyah Journal of Pharmaceutical Sciences ◽

10.32947/ajps.20.01.0442 ◽

2020 ◽

pp. 82-94

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Pharmaceutical Care ◽

Biochemical Parameters ◽

Positive Impact ◽

Potential Effect ◽

Care Group ◽

Mineral Bone Disorder ◽

Bone Disorder

Objective: the present study was aimed to evaluate the role of pharmaceutical services in improving the outcome of mineral bone disorder in patients with advanced chronic kidney disease. Methodology: One hundred and twenty patients with chronic kidney disease-mineral bone disorder (CKD-MBD) screened for eligibility, seventy-six patients enrolled in the study and randomly allocated into two groups: pharmaceutical care and usual care, both groups interviewed by the pharmacist using specific questionnaire for assessing the quality of life (QoL). All the drug related problems (DRPs) including drug-drug interactions (DDIs) were recorded by the pharmacist. Blood samples were collected and utilized for analyzing the levels of vitamin D, phosphorous, calcium, albumin and parathyroid hormone at baseline and three months after. The pharmaceutical care group received all the educations about their medications and how to minimize DRPs; improve the QoL. Additionally, the pharmaceutical intervention included correcting the biochemical parameters. Results: Pharmaceutical care significantly improved patients QoL and minimized DRPs and DDIs. It was also effective in improving the biochemical parameters. Conclusion: Pharmaceutical care has a positive impact on improving the outcome of patients with CKD-MBD through attenuating DRPs, improving the biochemical parameters and the QoL.

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