scholarly journals Whether Prolyl Hydroxylase Blocker—Roxadustat—In the Treatment of Anemia in Patients with Chronic Kidney Disease Is the Future?

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.

scholarly journals Novel Masters of Erythropoiesis: Hypoxia Inducible Factors and Recent Advances in Anemia of Renal Disease

2016 ◽  
Vol 42 (2) ◽  
pp. 160-167 ◽  
Author(s):  
Yalcin Solak ◽  
Mustafa Cetiner ◽  
Dimitrie Siriopol ◽  
Kayhan Tarim ◽  
Baris Afsar ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Phase 1 ◽  
Experimental Studies ◽  
Primary Treatment ◽  
Hypoxia Inducible Factors ◽  
Anemia Of Chronic Disease ◽  
Clinical Observations ◽  
Special Patient Population

Anemia seen in patients with chronic kidney disease is a particular form of ‘anemia of chronic disease'. Although multifactorial in origin, erythropoiesis-stimulating agents (ESAs) and adjuvant iron therapy represent the primary treatment for anemia in chronic kidney disease. Subsequent clinical observations revealed that these ESA hyporesponsive patients often had increased systemic inflammation as a consequence of their comorbidities. Use of high ESA doses to overcome this ESA hyporesponsiveness posed some concerns regarding associated adverse events of therapy and increased mortality in this special patient population. Recognizing the pivotal roles of hypoxia inducible factors (HIFs) in orchestrating elements of erythropoiesis opened new avenues in the management of renal anemia. Several phase 1 and 2 studies confirmed the results of early experimental studies supporting the beneficial role of augmenting HIFs for erythropoiesis. In this review, we describe the physiologic functions of HIF in erythropoiesis with special emphasis on interactions with iron and hepcidin metabolism and inflammation.

CLINICAL AND THERAPEUTIC VALUE OF ADIPOKINES IN PATIENTS WITH CHRONIC KIDNEY DISEASE

2020 ◽  
pp. 5-9
Author(s):  
Ya. M Fylenko
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Adipose Tissue ◽  
Kidney Disease ◽  
Therapeutic Potential ◽  
Interdisciplinary Approach ◽  
Blood Lipid ◽  
The Body ◽  
Incidence And Mortality

This review is devoted to the analysis of the role of adipokines in formation of pathological changes in renal function and structure. The patients with chronic kidney disease have a high risk of cardiovascular disease. Currently, the role of systemic hormonal and metabolic factors in the pathogenesis of the kidneys is growing. A promising area of pathogenetic prevention and treatment of kidney disease is an interdisciplinary approach, whereat the adipokine imbalance is of particular interest. Adipose tissue and its messengers, adipokines, are known to be highly associated with kidney disease. Adipocytes are metabolically active cells, producing the signaling lipids, metabolites and protein factors, i.e. adipokines. The interaction of adipose tissue with the kidney is called the adipose kidney axis, being important for the normal functioning of the body, as well as its response to an injury. It has a strong therapeutic potential in respect of the growing rates of chronic kidney disease. Adipocyte hypertrophy is often accompanied by the development of tissue fibrosis, hypoxia, and secretion of pro−inflammatory cytokines (such as tumor necrosis factor or interleukin, which triggers the cell inflammation). Dysfunction of adipose tissue contributes to the development of cardiovascular disease at the local and systemic levels. Thus, for the early diagnosis of chronic kidney disease into the diagnostic program, in addition to the generally accepted indices, the determination of adipokines: for example, serum leptin, adiponectin, omentin, visfatin, microalbuminuria, blood lipid spectrum, intrarenal and functional status of the kidneys with the assessment of functional renal reserve is recommended to be included. Early detection of the disease, new approaches to its diagnosis and treatment can help in reducing the risk of a high incidence and mortality from renal disease. Key words: chronic kidney disease, nephropathy, adipokines, leptin, resistin, adiponectin, visfatin, omentin.

scholarly journals Anemia in Chronic Kidney Disease : Role of Hypoxia Inducible Factor Stabilizer

2021 ◽  
Vol 5 (5) ◽  
pp. 462-467
Author(s):  
Emilia ◽  
Zulkhair Ali
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Randomized Clinical Trials ◽  
Hypoxia Inducible Factor ◽  
Standard Of Care ◽  
Current Standard ◽  
Endogenous Erythropoietin ◽  
Red Blood Cell Transfusions ◽  
Erythropoietin Deficiency

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.

Exploring the role of excess fluoride in chronic kidney disease: A review

2018 ◽  
Vol 38 (3) ◽  
pp. 269-279 ◽  
Author(s):  
RW Dharmaratne
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Adverse Effects ◽  
Soft Tissues ◽  
Human Kidney ◽  
Kidney Damage ◽  
The Body ◽  
Excessive Consumption ◽  
The Impact

This review covers nearly 100 years of studies on the toxicity of fluoride on human and animal kidneys. These studies reveal that there are direct adverse effects on the kidneys by excess fluoride, leading to kidney damage and dysfunction. With the exception of the pineal gland, the kidney is exposed to higher concentrations of fluoride than all other soft tissues. Therefore, exposure to higher concentrations of fluoride could contribute to kidney damage, ultimately leading to chronic kidney disease (CKD). Among major adverse effects on the kidneys from excessive consumption of fluoride are immediate effects on the tubular area of the kidneys, inhibiting the tubular reabsorption; changes in urinary ion excretion by the kidneys disruption of collagen biosynthesis in the body, causing damages to the kidneys and other organs; and inhibition of kidney enzymes, affecting the functioning of enzyme pathways. This review proposes that there is a direct correlation between CKD and the consumption of excess amounts of fluoride. Studies particularly show immediate adverse effects on the tubular area of human and animal kidneys leading to CKD due to the consumption of excess fluoride. Therefore, it is very important to conduct more investigations on toxicity studies of excess fluoride on the human kidney, including experiments using human kidney enzymes, to study more in depth the impact of excess fluoride on the human kidney. Further, the interference of excess fluoride on collagen synthesis in human body and its effect on human kidney should also be further investigated.

Are prolyl-hydroxylase inhibitors potential alternative treatments for anaemia in patients with chronic kidney disease?

2019 ◽  
Vol 35 (6) ◽  
pp. 926-932 ◽  
Author(s):  
Francesco Locatelli ◽  
Lucia Del Vecchio
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Hypoxia Inducible Factor ◽  
Prolyl Hydroxylase ◽  
Adverse Outcomes ◽  
The Body ◽  
Phase Iii ◽  
Endogenous Erythropoietin ◽  
Potential Alternative

Abstract Prolyl-hydroxylase (PHD) inhibitors (PHD-I) are the most appealing drugs undergoing clinical development for the treatment of anaemia in patients with chronic kidney disease. PHD inhibition mimics the exposure of the body to hypoxia and activates the hypoxia-inducible factor system. Among many other pathways, this activation promotes the production of endogenous erythropoietin (EPO) and the absorption and mobilization of iron. PHD-I are given orally and, differing from erythropoiesis-stimulating agents (ESAs), they correct and maintain haemoglobin levels by stimulating endogenous EPO production. Their efficacy and safety are supported by several Phases I and II studies with relatively short follow-up. This class of drugs has the potential to have a better safety profile than ESAs and there may be additional advantages for cardiovascular disease (CVD), osteoporosis and metabolism. However, possible adverse outcomes are feared. These span from the worsening or occurrence of new cancer, to eye complications or pulmonary hypertension. The data from the ongoing Phase III studies are awaited to better clarify the long-term safety and possible advantages of PHD-I.

scholarly journals Role of Myeloperoxidase in Patients with Chronic Kidney Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Bojana Kisic ◽  
Dijana Miric ◽  
Ilija Dragojevic ◽  
Julijana Rasic ◽  
Ljiljana Popovic
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Public Health Problem ◽  
Cardiovascular Complications ◽  
The Body ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease (CKD) is a worldwide public health problem. Patients with CKD have a number of disorders in the organism, and the presence of oxidative stress and systemic inflammation in these patients is the subject of numerous studies. Chronic inflammation joined with oxidative stress contributes to the development of numerous complications: accelerated atherosclerosis process and cardiovascular disease, emergence of Type 2 diabetes mellitus, development of malnutrition, anaemia, hyperparathyroidism, and so forth, affecting the prognosis and quality of life of patients with CKD. In this review we presented the potential role of the myeloperoxidase enzyme in the production of reactive/chlorinating intermediates and their role in oxidative damage to biomolecules in the body of patients with chronic kidney disease and end-stage renal disease. In addition, we discussed the role of modified lipoprotein particles under the influence of prooxidant MPO intermediates in the development of endothelial changes and cardiovascular complications in renal failure.

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

2018 ◽  
Vol Volume 12 ◽  
pp. 3003-3011 ◽  
Author(s):  
Hongzhen zhong ◽  
Tianbiao Zhou ◽  
Hongyan Li ◽  
Zhiqing Zhong
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Hypoxia Inducible Factor

scholarly journals 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

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. 

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

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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