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https://www.readbyqxmd.com/read/29775888/therapeutic-impact-of-rhuepo-on-abnormal-platelet-app-bace-1-presenilin-1-adam-10-and-a%C3%AE-expressions-in-chronic-kidney-disease-patients-with-cognitive-dysfunction-like-alzheimer-s-disease-a-pilot-study
#1
Vinothkumar G, Krishnakumar S, Sureshkumar, Shivashekar G, Sreedhar S, Preethikrishnan, Dinesh S, Sundaram A, Balakrishnan D, Riya, Venkataraman P
BACKGROUND: Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29767854/emerging-association-between-parathyroid-hormone-and-anemia-in-hemodialysis-patients
#2
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/29746307/erythropoietin-mimetic-peptides-and-erythropoietin-fusion-proteins-for-treating-anemia-of-chronic-kidney-disease
#3
Nupur Gupta, Jay B Wish
PURPOSE OF REVIEW: First generation erythropoiesis stimulating agents (ESAs) have short duration of action which requires administration once weekly or greater. Second generation ESAs were developed which have longer duration of action and can be administered one to two times monthly. Erythropoietin (EPO) mimetic peptides (EMPs) activate the EPO receptor but have no structural analogy to EPO, offering the potential for lower cost as they are not biologic drugs. The first approved EMP, peginesatide, was withdrawn from the market within a year of its approval because of fatal anaphylactic reactions...
May 4, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29746306/source-and-microenvironmental-regulation-of-erythropoietin-in-the-kidney
#4
Karen A Nolan, Roland H Wenger
PURPOSE OF REVIEW: Historically, the identity of O2-sensing renal erythropoietin (Epo)-producing (REP) cells was a matter of debate. This review summarizes how recent breakthroughs in transgenic mouse and in-situ hybridization techniques have facilitated sensitive and specific detection of REP cells and accelerated advancements in the understanding of the regulation of renal Epo production in health and disease. RECENT FINDINGS: REP cells are a dynamically regulated unique subpopulation of tubulointerstitial cells with features of fibroblasts, pericytes and neurons...
May 8, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29742267/epoetin-alfa-resistance-in-hemodialysis-patients-with-chronic-kidney-disease-a-longitudinal-study
#5
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/29738538/the-hypoxia-inducible-factor-erythropoietin-epo-epo-receptor-pathway-is-disturbed-in-a-rat-model-of-chronic-kidney-disease-related-anemia
#6
Daniel Landau, Lital London, Inbar Bandach, Yael Segev
OBJECTIVES: Anemia is a known driver for hypoxia inducible factor (HIF) which leads to increased renal erythropoietin (EPO) synthesis. Bone marrow (BM) EPO receptor (EPOR) signals are transduced through a JAK2-STAT5 pathway. The origins of anemia of chronic kidney disease (CKD) are multifactorial, including impairment of both renal EPO synthesis as well as intestinal iron absorption. We investigated the HIF- EPO- EPOR axis in kidney, BM and proximal tibia in anemic juvenile CKD rats. METHODS: CKD was induced by 5/6 nephrectomy in young (20 days old) male Sprague-Dawley rats while C group was sham operated...
2018: PloS One
https://www.readbyqxmd.com/read/29712435/prolyl-hydroxylase-inhibitors-a-breakthrough-in-the-therapy-of-anemia-associated-with-chronic-diseases
#7
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/29704093/trends-in-the-treatment-of-chronic-kidney-disease-associated-anaemia-in-a-cohort-of-haemodialysis-patients-the-irish-experience
#8
Roisin Gardiner, Davood Roshan, Ann Brennan, Denise Connolly, Susan Murray, Donal Reddan
BACKGROUND: Anaemia among haemodialysis patients is treated with iron and erythropoietin-stimulating agents (ESAs). ESAs reduce requirements for blood transfusions but are also expensive and overzealous use may be associated with adverse outcomes. Recent international trends have been characterised by reduced ESA doses and a greater reliance on intravenous (IV) iron. We determined trends in prescribing patterns of ESAs and IV iron for the treatment of anaemia in two representative Irish dialysis centres and correlated with current guidelines and international trends...
April 27, 2018: Irish Journal of Medical Science
https://www.readbyqxmd.com/read/29697839/brain-derived-erythropoietin-protects-from-intermittent-hypoxia-induced-cardiorespiratory-dysfunction-and-oxidative-stress-in-mice
#9
Elizabeth Elliot-Portal, Sofien Laouafa, Christian Arias-Reyes, Tara Adele Janes, Vincent Joseph, Jorge Soliz
Study Objectives: Based on the fact that erythropoietin (Epo) administration in rodents protects against spatial learning and cognitive deficits induced by chronic intermittent hypoxia (CIH)-mediated oxidative damage, here we tested the hypothesis that Epo in the brain protects against cardiorespiratory disorders and oxidative stress induced by CIH in adult mice. Methods: Adult control and transgenic mice overexpressing Epo in the brain only (Tg21) were exposed to CIH (21%-10% O2-10 cycles/hour-8 hours/day-7 days) or room air...
April 25, 2018: Sleep
https://www.readbyqxmd.com/read/29668766/prediction-of-hemoglobin-levels-in-individual-hemodialysis-patients-by-means-of-a-mathematical-model-of-erythropoiesis
#10
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/29659573/whole-body-iron-transport-and-metabolism-mechanistic-multi-scale-model-to-improve-treatment-of-anemia-in-chronic-kidney-disease
#11
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
#12
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/29615029/a-chinese-herbal-decoction-jian-pi-yi-shen-regulates-the-expressions-of-erythropoietin-and-pro-inflammatory-cytokines-in-cultured-cells
#13
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/29575006/first-in-man-proof-of-concept-study-with-molidustat-a-novel-selective-oral-hif-prolyl-hydroxylase-inhibitor-for-the-treatment-of-renal-anaemia
#14
M Böttcher, S Lentini, E R Arens, A Kaiser, D van der Mey, U Thuss, D Kubitza, G Wensing
AIMS: Insufficient erythropoietin (EPO) synthesis is a relevant cause of renal anaemia in patients with chronic kidney disease. Molidustat, a selective hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, increases endogenous EPO levels dose-dependently in preclinical models. We examined the pharmacokinetics, safety, tolerability and the effect on EPO levels after single oral doses of molidustat in healthy male volunteers. METHODS: This was a single centre, randomized, single-blind, placebo-controlled, group-comparison, dose-escalation study...
March 25, 2018: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29569190/hif-stabilizers-in-the-management-of-renal-anemia-from-bench-to-bedside-to-pediatrics
#15
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/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
#16
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
https://www.readbyqxmd.com/read/29502007/comprehensive-glycan-analysis-of-twelve-recombinant-human-erythropoietin-preparations-from-manufacturers-in-china-and-japan
#17
Ben Cowper, Xiang Li, Lei Yu, Yong Zhou, W H Fan, C M Rao
Recombinant, human, erythropoietin (rhEPO) is a glycoprotein hormone which is prescribed throughout the world to treat anaemia caused by chronic kidney disease or chemotherapy. rhEPO is at the forefront of the recent emergence of biosimilar medicines, with numerous products now available worldwide. Due to its complex glycosylation profile, which has a crucial influence upon biological activity, therapeutic rhEPO preparations must be closely monitored to ensure consistency, safety and efficacy. Here, we have compared twelve rhEPO preparations from eleven manufacturers in China and one in Japan, measuring in vivo biological activity and exploring its relationship with glycosylation through sialic acid content determination, isoform distribution via capillary electrophoresis (CE), O-glycan profiling, and N-glycan mapping using a novel anion-exchange/hydrophilic interaction chromatography-mass spectrometry (AEX/HILIC-MS) approach...
May 10, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29485740/discovery-of-molidustat-bay-85-3934-a-small-molecule-oral-hif-prolyl-hydroxylase-hif-ph-inhibitor-for-the-treatment-of-renal-anemia
#18
Hartmut Beck, Mario Jeske, Kai Thede, Friederike Stoll, Ingo Flamme, Metin Akbaba, Jens-Kerim Ergüden, Gunter Karig, Jörg Keldenich, Felix Oehme, Hans-Christian Militzer, Ingo V Hartung, Uwe Thuss
Small-molecule inhibitors of hypoxia-inducible factor prolyl hydroxylases (HIF-PHs) are currently under clinical development as novel treatment options for chronic kidney disease (CKD) associated anemia. Inhibition of HIF-PH mimics hypoxia and leads to increased erythropoietin (EPO) expression and subsequently increased erythropoiesis. Herein we describe the discovery, synthesis, structure-activity relationship (SAR), and proposed binding mode of novel 2,4-diheteroaryl-1,2-dihydro-3H-pyrazol-3-ones as orally bioavailable HIF-PH inhibitors for the treatment of anemia...
February 28, 2018: ChemMedChem
https://www.readbyqxmd.com/read/29481308/inhibition-of-fibroblast-growth-factor-23-fgf23-signaling-rescues-renal-anemia
#19
Rafiou Agoro, Anna Montagna, Regina Goetz, Onyedikachi Aligbe, Gurinder Singh, Lindsay M Coe, Moosa Mohammadi, Stefano Rivella, Despina Sitara
Severe anemia and iron deficiency are common complications in chronic kidney disease. The cause of renal anemia is multifactorial and includes decreased erythropoietin (Epo) production, iron deficiency, and inflammation, and it is currently treated with injections of synthetic Epo. However, the use of recombinant Epo has several adverse effects. We previously reported that high fibroblast growth factor 23 (FGF23) levels in mice are associated with decreased red blood cell production, whereas genetic inactivation of Fgf23 results in expansion of the erythroid lineage...
February 26, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29465053/erythropoietic-response-to-anaemia-of-dialysis-na%C3%A3-ve-patients-with-chronic-kidney-disease-in-zaria-north-west-nigeria
#20
L G Dogara, A Hassan, S Awwalu, L Okpetu, A D Waziri, A A Babadoko, I B Bosan, H M Muktar
Introduction: Chronic kidney disease (CKD) is a global health problem with an increasing prevalence worldwide. Anemia is one of its consistent and severe hematological complications although its mechanism is not fully elucidated. The primary defect could manifest as serum erythropoietin (sEPO) deficiency or EPO resistance. We set out to determine the erythropoietic response to anemia of patients with CKD and its relationship with their iron status in a cross-sectional descriptive study of 91 patients in various stages of CKD...
February 2018: Nigerian Journal of Clinical Practice
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