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https://www.readbyqxmd.com/read/28928122/discovery-and-preclinical-characterization-of-gsk1278863-daprodustat-a-small-molecule-hypoxia-inducible-factor-hif-prolyl-hydroxylase-inhibitor-for-anemia
#1
Jennifer L Ariazi, Kevin J Duffy, David F Adams, Duke M Fitch, Lusong Luo, Melissa Pappalardi, Mangatt Biju, Erin Hugger DiFilippo, Tony Shaw, Ken Wiggall, Connie Erickson-Miller
Decreased erythropoietin (EPO) production, shortened erythrocyte survival, and other factors reducing the response to EPO contribute to anemia in patients with a variety of underlying pathologies such as chronic kidney disease (CKD). Treatment with recombinant human EPO (rHuEPO) at supraphysiological concentrations has proven to be efficacious. However, it does not ameliorate the condition in all patients and presents its own risks, including cardiovascular complications. The transcription factors hypoxia-inducible factor (HIF)1α and HIF2α control the physiological response to hypoxia and invoke a program of increased erythropoeisis...
September 19, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28915563/niaoduqing-granules-relieve-chronic-kidney-disease-symptoms-by-decreasing-renal-fibrosis-and-anemia
#2
Xu Wang, Suyun Yu, Qi Jia, Lichuan Chen, Jinqiu Zhong, Yanhong Pan, Peiliang Shen, Yin Shen, Siliang Wang, Zhonghong Wei, Yuzhu Cao, Yin Lu
NiaoDuQing (NDQ) granules, a traditional Chinese medicine, has been clinically used in China for over fourteen years to treat chronic kidney disease (CKD). To elucidate the mechanisms underlying the therapeutic benefits of NDQ, we designed an approach incorporating chemoinformatics, bioinformatics, network biology methods, and cellular and molecular biology experiments. A total of 182 active compounds were identified in NDQ granules, and 397 putative targets associated with different diseases were derived through ADME modelling and target prediction tools...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28904872/treatment-of-renal-anemia-erythropoiesis-stimulating-agents-and-beyond
#3
REVIEW
Patrick Biggar, Gheun-Ho Kim
Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10-11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events...
September 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28857467/impaired-erythropoietin-synthesis-in-chronic-kidney-disease-is-caused-by-alterations-in-extracellular-matrix-composition
#4
Gemma Olmos, José M Muñoz-Félix, Inés Mora, Anton Gerhard Müller, Maria Piedad Ruiz-Torres, José M López-Novoa, Diego Rodríguez-Puyol
Renal fibrosis and anaemia are two of the most relevant events in chronic kidney disease. Fibrosis is characterized by the accumulation of extracellular matrix proteins in the glomeruli and tubular interstitium. Anaemia is the consequence of a decrease in erythropoietin production in fibrotic kidneys. This work analyses the possibility that the accumulation of abnormal collagens in kidney interstitium could be one of the mechanisms responsible for erythropoietin decreased synthesis. In renal interstitial fibroblast grown on collagen I, erythropoietin mRNA expression and HIF-2α protein decreased, whereas focal adhesion kinase protein (FAK) phosphorylation and proteasome activity increased, compared to cells grown on collagen IV...
August 30, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28792166/evaluation-of-effect-of-ascorbic-acid-on-ferritin-and-erythropoietin-resistance-in-patients-of-chronic-kidney-disease
#5
N Nand, A R Deshmukh, R Mittal
OBJECTIVE: This study was planned to evaluate the effect of short term intravenous ascorbic acid on reducing ferritin and erythropoietin resistance in patients of chronic kidney disease (CKD) on maintenance haemodialysis (MHD). METHODS: Forty adult patients [20 patients in group A with increased serum ferritin level (>500 ng/ml), transferrin saturation (TSAT) ≤20% and 20 patients in group B with normal serum ferritin level (<200 ng/ml), TSAT ≤20%] of end stage renal disease (ESRD) with erythropoietin hyporesponsiveness undergoing maintenance hemodialysis were included in the study...
July 2017: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/28766493/evaluation-of-the-safety-and-immunogenicity-of-subcutaneous-hx575-epoetin-alfa-in-the-treatment-of-anemia-associated-with-chronic-kidney-disease-in-predialysis-and-dialysis-patients%C3%A2
#6
Nicole Casadevall, Vladimir Dobronravov, Kai-Uwe Eckardt, Sehsuvar Ertürk, Liliya Martynyuk, Susanne Schmitt, Gregor Schaffar, Anita Rudy, Andriy Krendyukov, Marité Ode
AIM: To assess the safety and immunogenicity of subcutaneous (SC) HX575 (epoetin-α) in dialysis- and nondialysis-dependent adult patients with chronic kidney disease (CKD). METHODS: Open-label, single-arm, multicenter study in patients (n = 416) from Germany, Italy, Poland, Romania, Russia, Turkey, and Ukraine. RESULTS: Mean (standard deviation (SD)) age was 52.3 (15.8) years, all patients were Caucasian, and similar proportions were male/female...
August 2, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/28757635/mechanisms-and-consequences-of-carbamoylation
#7
REVIEW
Sigurd Delanghe, Joris R Delanghe, Reinhart Speeckaert, Wim Van Biesen, Marijn M Speeckaert
Protein carbamoylation is a non-enzymatic post-translational modification that binds isocyanic acid, which can be derived from the dissociation of urea or from the myeloperoxidase-mediated catabolism of thiocyanate, to the free amino groups of a multitude of proteins. Although the term 'carbamoylation' is usually replaced by the term "carbamylation" in the literature, carbamylation refers to a different chemical reaction (the reversible interaction of CO2 with α and ε-amino groups of proteins). Depending on the altered molecule (for example, collagen, erythropoietin, haemoglobin, low-density lipoprotein or high-density lipoprotein), carbamoylation can have different pathophysiological effects...
September 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28753201/delivery-of-human-erythropoietin-gene-with-an-adeno-associated-virus-vector-through-parotid-glands-to-treat-renal-anaemia-in-a-swine-model
#8
C Ma, Z Fan, Z Gao, S Wang, Z Shan
Anaemia is a common complication of chronic kidney disease, for which there is presently no adequate treatment. The delivery of human erythropoietin (hEPO) cDNA to salivary glands reportedly increases red blood cell counts, haematocrit (HCT), and haemoglobin concentration, representing a potential new method of renal anaemia treatment. However, no studies have examined the effects of this method in an animal model of renal anaemia. Here we established a miniature pig animal model of renal anaemia through continuous feeding with adenine...
July 28, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28717516/costs-associated-with-intravenous-darbepoetin-versus-epoetin-therapy-in-hemodialysis-patients-a-randomized-controlled-trial
#9
Andrea L Woodland, Sean W Murphy, Bryan M Curtis, Brendan J Barrett
BACKGROUND: Anemia of chronic kidney disease is associated with adverse outcomes and a reduced quality of life. Erythropoiesis-stimulating agents (ESAs) have improved anemia management, and 2 agents are available in Canada, epoetin alfa (EPO) and darbepoetin alfa (DA). EPO and DA are considered equally effective in achieving target hemoglobin (Hb), but it is not clear whether there is a cost difference. There have been few head-to-head comparisons; most published studies are observational switch studies...
2017: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/28705055/ferrokinetics-is-associated-with-the-left-ventricular-mass-index-in-patients-with-chronic-kidney-disease
#10
Akihito Tanaka, Daijo Inaguma, Yu Watanabe, Eri Ito, Naoki Kamegai, Hiroya Shimogushi, Hibiki Shinjo, Kiyomi Koike, Yasuhiro Otsuka, Asami Takeda
Background Patients with chronic kidney disease (CKD) often have the complication of anaemia. Usage of an erythropoietin-stimulating agent accelerates iron deficiency because it promotes iron utilization. Recently, iron administration was reported to be effective for patients with cardiac failure. We examined the association between ferrokinetics and cardiac function in patients with CKD. Methods In this cross-sectional study, we examined 558 patients (424 men and 134 women; mean age, 68.9 ± 13.1 years) with CKD who were admitted to our hospital...
July 14, 2017: Acta Cardiologica
https://www.readbyqxmd.com/read/28682026/-clinical-management-of-anemia-in-patients-with-ckd
#11
Rodolfo Fernando Rivera, Maria Teresa Sciarrone Alibrandi, Luca Di Lullo, Fulvio Fioccari
Anemia is a frequent complication in chronic kidney disease (CKD), and it is often accompanied by various clinical symptoms. The primary cause of anemia in CKD patients is the reduction in the erythropoietin production, which results in a decrease of signaling molecule that stimulates red blood cell production. Other possible causes of anemia in CKD include iron deficiency, inflammation, and the accumulation of uremic toxin. This chapter focuses the discussion on the strategy of the management of anemia in patients with CKD...
March 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28680358/interpretation-of-erythropoietin-and-haemoglobin-levels-in-patients-with-various-stages-of-chronic-kidney-disease
#12
Mirsad Panjeta, Ismet Tahirović, Emin Sofić, Jozo Ćorić, Amela Dervišević
BACKGROUND: The production of erythrocytes is regulated by the hormone erythropoietin (EPO), which maintains the blood haemoglobin (Hb) levels constant under normal conditions. Human EPO is a glycoprotein hormone and its synthesis is controlled by the hypoxia-inducible transcription factor. The aim of this study was to establish EPO and Hb levels in patients with chronic kidney disease (CKD), as well as in control subjects, and to investigate the relationship between these parameters...
April 2017: Journal of Medical Biochemistry
https://www.readbyqxmd.com/read/28674560/-management-of-chronic-hemodialysis-patients-with-anemia-case-study-conducted-in-the-department-of-nephrology-and-hemodialysis-at-the-university-hospital-point-g-in-mali
#13
Alhadji Ahmadou Tounkara, Abdoul Mahama Sériba Coulibaly, Nouhoun Coulibaly, Békaye Traoré, Mahamane Kalil Maïga
INTRODUCTION: Anemia is a frequent complication of Chronic Kidney Disease CKD commonly found in chronic haemodialysis patients. Patients management is mainly based on erythropoietin administration and iron supplementation. This study aimed to evaluate the management of chronic hemodialysis patients with anemia in the Department of Nephrology and Hemodialysis at the University Hospital Point G in Mali. METHODS: We conducted a cross-sectional study from 1 to 31 August 2016...
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28669019/altered-expression-of-intestinal-duodenal-cytochrome-b-and-divalent-metal-transporter-1-might-be-associated-with-cardio-renal-anemia-syndrome
#14
Yoshiro Naito, Hisashi Sawada, Makiko Oboshi, Keisuke Okuno, Seiki Yasumura, Yoshitaka Okuhara, Akiyo Eguchi, Koichi Nishimura, Yuko Soyama, Masanori Asakura, Masaharu Ishihara, Takeshi Tsujino, Tohru Masuyama
The interaction among heart failure (HF), chronic kidney disease (CKD), and anemia is called cardio-renal anemia syndrome. The mechanism of anemia in cardio-renal anemia syndrome is complex and remains completely unknown. We have previously reported that impaired intestinal iron transporters may contribute to the mechanism of anemia in HF using in vivo HF model rats. In this study, we assessed intestinal iron transporters in CKD model rats to investigate the association of intestinal iron transporters in the mechanism of cardio-renal anemia syndrome...
July 1, 2017: Heart and Vessels
https://www.readbyqxmd.com/read/28660446/rationale-and-design-of-observational-clinical-research-in-chronic-kidney-disease-patients-with-renal-anemia-renal-prognosis-in-patients-with-hyporesponsive-anemia-to-erythropoiesis-stimulating-agents-darbepoetin-alfa-brighten-trial
#15
Hideki Kato, Masaomi Nangaku, Hideki Hirakata, Takashi Wada, Terumasa Hayashi, Hiroshi Sato, Yasushi Yamazaki, Takao Masaki, Tatsuo Kagimura, Hiroyasu Yamamoto, Hiroki Hase, Masahiro Kamouchi, Enyu Imai, Kyoichi Mizuno, Manabu Iwasaki, Tadao Akizawa, Yoshiharu Tsubakihara, Shoichi Maruyama, Ichiei Narita
BACKGROUND: Renal anemia is an important complication in non-dialysis chronic kidney disease (CKD) patients as well as in dialysis patients. Although recombinant human erythropoietin has dramatically improved prognosis and quality of life in these patients, there have been issues among non-dialysis CKD patients who exhibit hyporesponsiveness to erythropoiesis-stimulating agent (ESA). The causes and definition of ESA hyporesponsiveness, as well as the incidence of renal and cardiovascular disease (CVD) events in such patients, are yet to be clarified...
June 28, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/28652624/serum-hepcidin-may-be-a-novel-uremic-toxin-which-might-be-related-to-erythropoietin-resistance
#16
Sung Woo Lee, Jeong Min Kim, Hye Jin Lim, Young-Hwan Hwang, Soo Wan Kim, Wookyung Chung, Kook-Hwan Oh, Curie Ahn, Kyu-Beck Lee, Su Ah Sung
The clinical importance of serum hepcidin in non-dialysis chronic kidney disease (CKD) patients is unclear. The database of a large-scale multicentre prospective study in Korea of 2238 patients enrolled from 2011-2016 was analysed. After excluding patients with missing serum hepcidin (n = 125) and haemoglobin (n = 23) levels, the study included 2090 non-dialysis CKD patients. Markers of inflammation and iron status were positively associated with serum hepcidin level, regardless of CKD stage. However, estimated glomerular filtration rate was inversely associated with serum hepcidin level, particularly in patients with CKD stages 3b-5 but not in those with CKD stages 1-3a...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28651951/prolyl-hydroxylase-domain-inhibitors-as-a-novel-therapeutic-approach-against-anemia-in-chronic-kidney-disease
#17
Mai Sugahara, Tetsuhiro Tanaka, Masaomi Nangaku
Anemia is a common complication of chronic kidney disease and is mainly caused by the inability of injured kidneys to produce adequate amounts of erythropoietin. Studies elucidating the regulation of erythropoietin production led to the identification of hypoxia-inducible factor (HIF), which activates the transcription of genes that mediate adaptive responses to hypoxia. HIF is a heterodimer that consists of an α and β subunit. While HIF-β is constitutively expressed, HIF-α is subjected to ubiquitination and proteasomal degradation under normoxic conditions...
August 2017: Kidney International
https://www.readbyqxmd.com/read/28646375/comparative-efficacy-and-safety-in-esa-biosimilars-vs-originators-in-adults-with-chronic-kidney-disease-a-systematic-review-and-meta-analysis
#18
REVIEW
Laura Amato, Antonio Addis, Rosella Saulle, Francesco Trotta, Zuzana Mitrova, Marina Davoli
BACKGROUND: Several Erythropoiesis-stimulating agents (ESAs) are available to treat anemia in patients with chronic kidney disease (CKD). Questions about the comparability of such therapeutic options are not purely a regulatory or economical matter. Appropriate use of originator or biosimilar in these patients need to be supported by clinical data. Regarding the prevention of blood transfusion, reduction of fatigue, breathlessness and mortality or cardiovascular events, a summary of the comparative efficacy and safety data of these drugs is lacking...
June 23, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28636542/niaoduqing-granules-relieve-chronic-kidney-disease-symptoms-by-decreasing-renal-fibrosis-and-anemia
#19
Xu Wang, Suyun Yu, Qi Jia, Lichuan Chen, Jinqiu Zhong, Yanhong Pan, Peiliang Shen, Yin Shen, Siliang Wang, Zhonghong Wei, Yuzhu Cao, Yin Lu
NiaoDuQing (NDQ) granules, a traditional Chinese medicine, has been clinically used in China for over fourteen years to treat chronic kidney disease (CKD). To elucidate the mechanisms underlying the therapeutic benefits of NDQ, we designed an approach incorporating chemoinformatics, bioinformatics, network biology methods, and cellular and molecular biology experiments. A total of 182 active compounds were identified in NDQ granules, and 397 putative targets associated with different diseases were derived through ADME modelling and target prediction tools...
June 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28629513/erythropoietin-and-hypothalamic-pituitary-axis
#20
Soumyadeep Dey, Constance T Noguchi
Erythropoietin (EPO), known primarily for its erythropoietic activity, is commonly used clinically to treat anemia of chronic kidney disease. However, the expression of EPO receptor (EpoR) beyond erythroid tissue provides for potential extrahematopoietic effects of EPO, including EPO regulation of metabolic homeostasis (Zhang et al., 2014). Small clinical studies have shown that EPO treatment in patients with end-stage renal disease improved glycemic control and insulin sensitivity. Studies in animal models have shown that EPO regulation of metabolism is mainly attributed to its response in fat, and the hypothalamus-pituitary axis (Dey et al...
2017: Vitamins and Hormones
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