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anemia treatment in ckd

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https://www.readbyqxmd.com/read/29767854/emerging-association-between-parathyroid-hormone-and-anemia-in-hemodialysis-patients
#1
REVIEW
Motoko Tanaka, Hirotaka Komaba, Masafumi Fukagawa
Anemia is a common complication of chronic kidney disease (CKD). There are various causes of renal anemia such as decreased production of erythropoietin, resistance to erythropoietin, shortened survival of red blood cells, and bone marrow fibrosis. Secondary hyperparathyroidism (SHPT) is a less recognized, but potentially significant cause of renal anemia in CKD patients. Parathyroid hormone (PTH) has been regarded as a uremic toxin that has multiple adverse effects, and its elevated levels have been associated with renal anemia in hemodialysis patients...
May 16, 2018: Therapeutic Apheresis and Dialysis
https://www.readbyqxmd.com/read/29761242/safety-and-efficacy-of-benzbromarone-and-febuxostat-in-hyperuricemia-patients-with-chronic-kidney-disease-a-prospective-pilot-study
#2
Haibo Yu, Xinying Liu, Yaxiang Song, Jiafen Cheng, Hui Bao, Ling Qin, Xuan Zhou, Ling Wang, Ai Peng
BACKGROUND: To compare the safety and efficacy of benzbromarone and febuxostat in hyperuricemia patients with estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m2 . METHODS: This study was a single-centered, parallel-grouped, randomized clinical trial (RCT). We randomly assigned hyperuricemia participants with eGFR 20-60 mL/min/1.73 m2 into benzbromarone and febuxostat treatment group. Drugs were adjusted by titration from small doses. RESULTS: Seventy-three eligible participants enrolled, 66 subjects (33 in each group) were included finally for analysis...
May 14, 2018: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29755339/therapeutic-potential-of-a-prolyl-hydroxylase-inhibitor-fg-4592-for-parkinson-s-diseases-in-vitro-and-in-vivo-regulation-of-redox-biology-and-mitochondrial-function
#3
Xuan Li, Xin-Xin Cui, Ya-Jing Chen, Ting-Ting Wu, Huaxi Xu, Huiyong Yin, Yun-Cheng Wu
As the main transcription factor that regulates the cellular responses to hypoxia, Hypoxia-inducible factor-1α (HIF-1α) plays an important role in the pathogenesis of Parkinson's disease (PD). HIF-1α is normally degraded through ubiquitination after hydroxylation by prolyl hydroxylases (PHD). Emerging evidence has suggested that HIF PHD inhibitors (HIF-PHI) may have neuroprotective effects on PD through increasing HIF-1α levels. However, the therapeutic benefit of HIF-PHI for PD remains poorly explored due to the lack of proper clinical compounds and understanding of the underlying molecular mechanisms...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29753402/hif-activation-against-cvd-in-ckd-novel-treatment-opportunities
#4
REVIEW
Tetsuhiro Tanaka, Kai-Uwe Eckardt
Cardiovascular disease is a common and serious complication in patients with chronic kidney disease (CKD). One of the fundamental functions of the cardiovascular system is oxygen delivery, therefore cardiovascular disease inherently is linked to insufficient tissue oxygenation. Advances in our knowledge of cellular oxygen sensing by a family of prolyl hydroxylases (PHDs) and their role in regulating hypoxia-inducible factors (HIFs) have led to the discovery of PHD inhibitors as HIF stabilizers. Several small-molecule PHD inhibitors are currently in clinical trials for the treatment of anemia in CKD...
May 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29752643/effect-of-multiple-doses-of-omeprazole-on-the-pharmacokinetics-safety-and-tolerability-of-roxadustat-in-healthy-subjects
#5
Dorien Groenendaal-van de Meent, Martin den Adel, Jan van Dijk, Begona Barroso-Fernandez, Rachid El Galta, Georg Golor, Marloes Schaddelee
BACKGROUND AND OBJECTIVES: Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of anemia in chronic kidney disease. This study investigated the effect of multiple daily oral doses of omeprazole on the pharmacokinetics, safety, and tolerability of a single oral dose of roxadustat. METHODS: This phase 1, open-label, two-period, one-sequence, crossover study enrolled healthy subjects. During Period 1, subjects received a single oral dose of 100 mg roxadustat...
May 11, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29742267/epoetin-alfa-resistance-in-hemodialysis-patients-with-chronic-kidney-disease-a-longitudinal-study
#6
E J F Santos, E V Hortegal, H O Serra, J S Lages, N Salgado-Filho, A M Dos Santos
Anemia is an inevitable complication of hemodialysis, and the primary cause is erythropoietin deficiency. After diagnosis, treatment begins with an erythropoiesis-stimulating agent (ESA). However, some patients remain anemic even after receiving this medication. This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016...
2018: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/29734154/treatment-of-posttransplantation-anemia
#7
Kohei Unagami, Masayoshi Okumi, Tomomi Tamura, Hideki Ishida, Kazunari Tanabe, Kosaku Nitta
Kidney transplantation represents a renal replacement therapy for end-stage renal failure, with outcomes improving from year to year. With the improved survival prognosis, treatment of complications of chronic kidney disease after transplantation is becoming increasingly important. In particular, posttransplantation anemia (PTA) is often protracted, which could be related to a variety of factors, including the renal function status, graft rejection episodes, and infectious causes. PTA occurs in about 30-40% of transplant recipients, and is known to affect the function of the transplanted kidney as well as patient survival...
2018: Contributions to Nephrology
https://www.readbyqxmd.com/read/29712435/prolyl-hydroxylase-inhibitors-a-breakthrough-in-the-therapy-of-anemia-associated-with-chronic-diseases
#8
Amit Arvind Joharapurkar, Vrajesh Bhaskarbhai Pandya, Vishal J Patel, Ranjit C Desai, Mukul R Jain
Chronic kidney disease, cancer, chronic inflammatory disorders, nutritional and genetic deficiency can cause anemia. Hypoxia causes induction of hypoxia-inducible factor (HIF), which stimulates erythropoietin (EPO) synthesis. Prolyl hydroxylase domain (PHD) enzyme inhibition can stabilize hypoxia-inducible factor (HIF). HIF stabilization also decreases hepcidin, a hormone of hepatic origin, which regulates iron homeostasis. PHD inhibitors represent the novel pharmacological treatment of anemia of chronic diseases...
May 1, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29703633/oral-versus-intravenous-iron-supplementation-for-the-treatment-of-iron-deficiency-anemia-in-patients-on-maintenance-hemodialysis-effect-on-fibroblast-growth-factor-23-metabolism
#9
Wataru Fukao, Yukiko Hasuike, Tomo Yamakawa, Kazuhiro Toyoda, Makoto Aichi, Satoko Masachika, Mari Kantou, Shoko Ikeda Takahishi, Takahide Iwasaki, Mana Yahiro, Masatoshi Nanami, Yasuyuki Nagasawa, Takahiro Kuragano, Takeshi Nakanishi
OBJECTIVE: Iron administration affects serum levels of intact (I-) fibroblast growth factor-23 (FGF23) and its cleavage product C-terminal (C-) FGF23 in iron-deficient patients on maintenance hemodialysis (MHD). The objective of this study was to compare the effect of oral or intravenous iron administration on serum levels of I-FGF23 and C-FGF23 in iron-deficient patients on MHD. DESIGN AND METHODS: A prospective randomized study. SUBJECTS: Participants on MHD with severe iron deficiency (n = 61)...
April 24, 2018: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/29672740/effects-of-vadadustat-on-hemoglobin-concentrations-in-patients-receiving-hemodialysis-previously-treated-with-erythropoiesis-stimulating-agents
#10
Volker H Haase, Glenn M Chertow, Geoffrey A Block, Pablo E Pergola, Emil M deGoma, Zeeshan Khawaja, Amit Sharma, Bradley J Maroni, Peter A McCullough
Background: Vadadustat, an inhibitor of hypoxia-inducible factor prolyl-4-hydroxylase domain dioxygenases, is an oral investigational agent in development for the treatment of anemia secondary to chronic kidney disease. Methods: In this open-label Phase 2 trial, vadadustat was evaluated in 94 subjects receiving hemodialysis, previously maintained on epoetin alfa. Subjects were sequentially assigned to one of three vadadustat dose cohorts by starting dose: 300 mg once daily (QD), 450 mg QD or 450 mg thrice weekly (TIW)...
April 16, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29668766/prediction-of-hemoglobin-levels-in-individual-hemodialysis-patients-by-means-of-a-mathematical-model-of-erythropoiesis
#11
Doris H Fuertinger, Franz Kappel, Hanjie Zhang, Stephan Thijssen, Peter Kotanko
Anemia commonly occurs in people with chronic kidney disease (CKD) and is associated with poor clinical outcomes. The management of patients with anemia in CKD is challenging, due to its severity, frequent hypo-responsiveness to treatment with erythropoiesis stimulating agents (ESA) and common hemoglobin cycling. Nonlinear dose-response curves and long delays in the effect of treatment on red blood cell population size complicate predictions of hemoglobin (Hgb) levels in individual patients. A comprehensive physiology based mathematical model for erythropoiesis was adapted individually to 60 hemodialysis patients treated with ESAs by identifying physiologically meaningful key model parameters from temporal Hgb data...
2018: PloS One
https://www.readbyqxmd.com/read/29666917/measurement-of-iron-status-in-chronic-kidney-disease
#12
Wesley Hayes
Anemia is a common complication of chronic kidney disease (CKD) in children, and dysregulation of iron homeostasis plays a central role in its pathogenesis. Optimizing iron status is a prerequisite for effective treatment of anemia. Insufficient iron can lead to inappropriate escalation of the erythropoiesis-stimulating agent (ESA) dose, which is associated with adverse outcomes. Excess iron supplementation also has negative sequelae including free radical tissue damage and increased risk of systemic infection...
April 17, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29659573/whole-body-iron-transport-and-metabolism-mechanistic-multi-scale-model-to-improve-treatment-of-anemia-in-chronic-kidney-disease
#13
Joydeep Sarkar, Alka A Potdar, Gerald M Saidel
Iron plays vital roles in the human body including enzymatic processes, oxygen-transport via hemoglobin and immune response. Iron metabolism is characterized by ~95% recycling and minor replenishment through diet. Anemia of chronic kidney disease (CKD) is characterized by a lack of synthesis of erythropoietin leading to reduced red blood cell (RBC) formation and aberrant iron recycling. Treatment of CKD anemia aims to normalize RBC count and serum hemoglobin. Clinically, the various fluxes of iron transport and accumulation are not measured so that changes during disease (e...
April 2018: PLoS Computational Biology
https://www.readbyqxmd.com/read/29655605/physiology-and-pathophysiology-of-renal-erythropoietin-producing-cells
#14
REVIEW
Hong-Mou Shih, Chih-Jen Wu, Shuei-Liong Lin
Anemia is a common complication and contributes to increased morbidity and mortality in chronic kidney disease (CKD) patients. Whereas there has been a significant improvement of understanding the underlying mechanism of erythropoiesis, the treatment of renal anemia is still restricted to erythropoietin (EPO)-stimulating agents. The purpose of this article is to review the physiology of erythropoiesis, functional role of EPO and underlying molecular and cellular basis that regulate EPO production. Regulation of EPO production is at mRNA level...
April 11, 2018: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/29624739/hemodialysis-induced-cardiovascular-disease
#15
REVIEW
Shadi Ahmadmehrabi, W H Wilson Tang
More than half of all deaths among end stage renal disease (ESRD) patients are due to cardiovascular disease (CVD). Cardiovascular changes secondary to renal dysfunction, including fluid overload, uremic cardiomyopathy, secondary hyperparathyroidism, anemia, altered lipid metabolism, and accumulation of gut microbiota-derived uremic toxins like trimethylamine N-oxidase, contribute to the high risk for CVD in the ESRD population. In addition, conventional hemodialysis (HD) itself poses myocardial stress and injury on the already compromised cardiovascular system in uremic patients...
April 6, 2018: Seminars in Dialysis
https://www.readbyqxmd.com/read/29615029/a-chinese-herbal-decoction-jian-pi-yi-shen-regulates-the-expressions-of-erythropoietin-and-pro-inflammatory-cytokines-in-cultured-cells
#16
Jianping Chen, Amy G W Gong, Xiaoyan Liu, Zhonggui Li, Airong Qi, Tina T X Dong, Tiegang Yi, Karl W K Tsim, Shunmin Li
BACKGROUND: A Chinese herbal formula, namely Jian-Pi-Yi-Shen (JPYS), has been clinically prescribed for patients with chronic kidney disease associated-anemia, and which can improve the patient's immunological system. However, the mechanisms of JPYS involved in anemia and immune response have not been investigated. To study the role of JPYS in regulating hematopoietic and immunological functions, we investigated its activities on the expressions of erythropoietin and pro-inflammatory cytokines in cultured cells...
April 3, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29581249/hypoxia-inducible-factor-prolyl-hydroxylase-inhibitor-roxadustat-fg-4592-protects-against-cisplatin-induced-acute-kidney-injury
#17
Yunwen Yang, Xiaowen Yu, Yue Zhang, Guixia Ding, Chunhua Zhu, Songming Huang, Zhanjun Jia, Aihua Zhang
Renal hypoxia occurs in acute kidney injury (AKI) of various etiologies. Activation of hypoxia-inducible transcription factor (HIF) has been identified as an important mechanism of cellular adaptation to low oxygen. Preconditional HIF activation protects against AKI, suggesting a new approach in AKI treatment. HIF is degraded under normoxic conditions mediated by oxygen-dependent hydroxylation of specific prolyl residues of the regulative α-subunits by HIF prolyl hydroxylases (PHD). FG-4592 is a novel, orally active small-molecule HIF PHD inhibitor for the treatment of anemia in patients with CKD...
March 26, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29569190/hif-stabilizers-in-the-management-of-renal-anemia-from-bench-to-bedside-to-pediatrics
#18
REVIEW
Dalvir Kular, Iain C Macdougall
Anemia is a common complication of chronic kidney disease (CKD) in adult and pediatric patients. It has traditionally been treated with erythropoietin therapy and iron supplementation, with great success. With the discovery of the major transcription factor hypoxia inducible factor (HIF) for the erythropoietin gene in 1992, molecules were created that inhibit the HIF prolyl-hydroxylase enzyme. This new class of drug-called HIF stabilizers, or HIF prolyl-hydroxylase inhibitors-prevents the proteasomal degradation of HIF-α, thereby inducing upregulation of the erythropoietin gene...
March 22, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29548780/social-determinants-of-health-addressing-unmet-needs-in-nephrology
#19
REVIEW
Yoshio N Hall
There is ongoing recognition that a wide array of social, economic, and environmental factors influence individuals' opportunities to engage in health care and healthy behaviors. Despite spending $34 billion annually on the care of patients with end-stage renal disease, the American public and nephrology community remain remarkably complacent about addressing "upstream" factors that influence the prevention, progression, and treatment of chronic kidney diseases. Recently, a growing number of health plans and dialysis providers have begun to embrace population health management; accept greater accountability for health, health care, and health costs; and envision kidney health beyond their traditional roles in care delivery...
March 13, 2018: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29544446/prevalence-treatment-patterns-and-healthcare-resource-utilization-in-medicare-and-commercially-insured-non-dialysis-dependent-chronic-kidney-disease-patients-with-and-without-anemia-in-the-united-states
#20
Wendy L St Peter, Haifeng Guo, Shaum Kabadi, David T Gilbertson, Yi Peng, Trudy Pendergraft, Suying Li
BACKGROUND: Anemia is common in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients, but detailed information on prevalence and treatment is lacking. METHODS: We evaluated anemia prevalence and treatment using two datasets: the Medicare 20% random sample (ages 66-85 years), and the Truven Health MarketScan database (ages 18-63 years). We selected stage 3-5 NDD-CKD patients with and without anemia from both databases during 2011-2013. We evaluated anemia prevalence and treatment (erythropoietin stimulating agents [ESAs], intravenous [IV] iron, red blood cell [RBC] transfusions) following anemia diagnosis during a 1-year baseline period, and healthcare utilization during a 1-year follow-up period...
March 15, 2018: BMC Nephrology
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