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Renal Anemia

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By Isabel Acosta-Ochoa Nephrology senior staff. Valladolid. Spain
Hara T Georgatzakou, Vassilis L Tzounakas, Athanassios D Velentzas, Issidora S Papassideri, Apostolos C Kokkalis, Konstantinos E Stamoulis, Anastasios G Kriebardis, Marianna H Antonelou
BACKGROUND: Despite universal administration of erythropoiesis-stimulating agents, patients with end-stage renal disease (ESRD) are at high risk for presenting persistent anemia. Due to ambiguities in optimal hemoglobin targets and evidence of recombinant human erythropoietin (EPO)-related toxicity, an increase in blood transfusions has been observed in chronic renal disease over the past years. The probable effects of uremic plasma on the performance of stored red blood cells (RBCs) after transfusion have not been investigated...
March 19, 2019: Transfusion
Christina Awad, Karin Gilkison, Erwin Shaw
Lanthanum carbonate is a phosphate binder that is used to reduce serum phosphate levels in patients with end-stage renal disease (ESRD). Lanthanum forms insoluble lanthanum phosphate complexes that are supposed to pass through the gastrointestinal (GI) tract unabsorbed. Phosphate binders have been reported to deposit in the GI tract and can cause mucosal injury. There are few case reports of GI bleeding associated with phosphate binder deposits. This case report presents a patient with iron deficiency anaemia secondary to biopsy-proven lanthanum deposits in the upper GI tract...
March 15, 2019: BMJ Case Reports
Aishatu Mohammed Nalado, Johnny N Mahlangu, Bala Waziri, Raquel Duarte, Graham Paget, Gbenga Olorunfemi, Saraladevi Naicker
Introduction: Anemia is a complication of chronic kidney disease (CKD) that can greatly impact on its prognosis. However, the risk factors for anemia, including the influence of ethnicity, are not well established among the CKD population in Johannesburg. Methods: This was a cross-sectional study of 353 adult CKD patients attending the renal outpatient clinic of the Charlotte Maxeke Johannesburg Academic Hospital (Johannesburg, South Africa) from June 1, 2016 to December 30, 2016...
2019: International Journal of Nephrology and Renovascular Disease
Tadao Akizawa, Iain C Macdougall, Jeffrey S Berns, Thomas Bernhardt, Gerald Staedtler, Megumi Taguchi, Kazuma Iekushi, Thilo Krueger
BACKGROUND: Molidustat, a novel hypoxia-inducible factor-prolyl hydroxylase inhibitor, is being investigated for the treatment of anemia associated with chronic kidney disease (CKD). The efficacy and safety of molidustat were recently evaluated in three 16-week phase 2b studies. Here, we report the results of two long-term extension studies of molidustat. METHODS: Both studies were parallel-group, open-label, multicenter studies of ≤36 months' duration, in patients with anemia due to CKD, and included an erythropoiesis-stimulating agent as active control...
March 8, 2019: American Journal of Nephrology
Francesco Locatelli, Lucia Del Vecchio
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...
March 7, 2019: Nephrology, Dialysis, Transplantation
Sohita Dhillon
Roxadustat (Ai Rui Zhuo® in China) is an orally administered, small molecule hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that is being developed by FibroGen, in collaboration with Astellas and AstraZeneca, for the treatment of anaemia in patients with dialysis-dependent chronic kidney disease (CKD), non-dialysis-dependent CKD and in patients with myelodysplastic syndromes. The drug reversibly binds to and inhibits HIF-prolyl hydroxylase enzymes that are responsible for the degradation of transcription factors in the HIF family under normal oxygen conditions...
February 25, 2019: Drugs
Amir Schechter, Anat Gafter-Gvili, Daniel Shepshelovich, Ruth Rahamimov, Uzi Gafter, Eytan Mor, Avry Chagnac, Benaya Rozen-Zvi
BACKGROUND: Post transplantation anemia (PTA) is common among kidney transplant patients. PTA is associated with increased graft loss and in most studies with increased mortality. However, the effect of the severity of anemia on this associations was not thoroughly evaluated. METHODS: Patients who underwent kidney transplantation in Rabin Medical Center (RMC) were included in the study. Data were collected during the years 2002-2016. Anemia was defined as hemoglobin (Hb) level less than 12 g/dL in women and less than 13 g/dL in men, in accordance with World Health Organization (WHO) criteria...
February 13, 2019: BMC Nephrology
Hongyong Liu, Yuqiu Ye, Yanbing Chen, Yunqiang Zhang, Shaomin Li, Wentao Hu, Rongqian Yang, Zhesi Zhang, Hongquan Peng, Linsheng Lv, Xun Liu
Anemia is one of the major complications in predialysis patients with chronic kidney disease (CKD). A clearer cognition of the prognostic impact of hemoglobin (Hb) or hematocrit (Hct) target on the outcomes of predialysis patients with CKD is significant. This article aims to establish the suitable hemoglobin target to provide clinical guidance. MEDLINE, EmBase, the Cochrane Library and other databases were searched with both MeSH terms and keywords to gather researches that assessed all-cause mortality, stroke, treatment of renal replacement, and transfusion...
February 11, 2019: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Amy M Meadowcroft, Borut Cizman, Louis Holdstock, Nandita Biswas, Brendan M Johnson, Delyth Jones, A Kaldun Nossuli, John J Lepore, Michael Aarup, Alexander R Cobitz
Background: This study evaluated the hemoglobin dose response, other efficacy measures and safety of daprodustat, an orally administered, hypoxia-inducible factor prolyl hydroxylase inhibitor in development for anemia of chronic kidney disease. Methods: Participants ( n  = 216) with baseline hemoglobin levels of 9-11.5 g/dL on hemodialysis (HD) previously receiving stable doses of recombinant human erythropoietin (rhEPO) were randomized in a 24-week dose-range, efficacy and safety study...
February 2019: Clinical Kidney Journal
Yuqiu Ye, Hongyong Liu, Yanbing Chen, Yunqiang Zhang, Shaomin Li, Wentao Hu, Rongqian Yang, Zhesi Zhang, Linsheng Lv, Xun Liu
BACKGROUND: Anemia is extremely common among dialysis patients and underlies some of the symptoms associated with reduced kidney function, including fatigue, depression, reduced exercise tolerance, and dyspnea. OBJECTIVES: A clearer cognition of the prognosistic impact of hemoglobin (Hb) or hematocrit (Hct) target for the outcomes of dialysis patients is urgent. This article aims to establish the suitable hemoglobin in order to provide clinical guidance. METHODS: MEDLINE, EmBase, the Cochrane Library and other databases were searched with both MeSH terms and keywords to gather randomized controlled trials that assessed all-cause mortality, cardiovascular events, fistula thrombosis, infectious diseases and transfusion among dialysis-dependent patients using erythropoiesis-stimulating agents...
November 2018: Renal Failure
Chi-Feng Pan, Cheng-Jui Lin, Shu-Hua Chen, Chi-Feng Huang, Chun-Chuan Lee
Anemia is common in chronic kidney disease (CKD) and may be affected by trace element concentrations. While the concentrations of trace elements are known to be altered in CKD, the relationship between trace element and hemoglobin concentrations has not been systematically investigated in a large cohort. This study aims to examine associations between trace element concentrations and anemia in patients with CKD. Data from the National Health and Nutrition Examination Survey collected from 2011 to 2014 were used for this analysis...
February 4, 2019: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Jay B Wish
No abstract text is available yet for this article.
April 2017: Nephrology News & Issues
Tadao Akizawa, Masaomi Nangaku, Takuhiro Yamaguchi, Masanobu Arai, Ryosuke Koretomo, Atsushi Matsui, Hideki Hirakata
BACKGROUND: Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that mimics adaptive responses to hypoxic conditions and may provide a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy, safety, and maintenance dose of enarodustat in anemic patients with CKD not on dialysis. METHODS: Erythropoiesis-stimulating agent (ESA) naïve patients (correction group) and patients on a stable dose of ESA (conversion group) were randomized to receive 2, 4, or 6 mg of enarodustat or placebo once daily for 6 weeks in a double-blind manner (Period 1) followed by 24 weeks of open enarodustat treatment to maintain their hemoglobin (Hb) levels within a target range of 10...
2019: American Journal of Nephrology
Daniel W Coyne, David Goldsmith, Iain C Macdougall
Anemia is a common complication of chronic kidney disease. Use of erythropoiesis-stimulating agents (ESA) has been a mainstay of treatment since 1990. A series of large trials demonstrated that ESAs have serious safety problems, including increasing cardiovascular and thrombotic events, and death. Analyses suggest high pharmacologic doses of ESAs, rather than the highly achieved hemoglobin, may mediate harm. Hypoxia-inducible factor (HIF) activators stimulate endogenous erythropoietin production and enhance iron availability...
December 2017: Kidney International Supplements
Matthew Sheetz, Philip Barrington, Sophie Callies, Paul H Berg, Juliet McColm, Thomas Marbury, Brian Decker, Gregory L Dyas, Stephanie M E Truhlar, Robert Benschop, Donmienne Leung, Jolene Berg, Derrick R Witcher
AIMS: Erythropoiesis stimulating agents (ESAs) used to treat anemia in patients with chronic kidney disease (CKD) has been associated with cardiovascular adverse events. Hepcidin production, controlled by BMP6, regulates iron homeostasis via interactions with the iron transporter, ferroportin. High hepcidin levels are thought to contribute to increased iron sequestration and subsequent anemia in CKD patients. To investigate alternative therapies to ESAs for CKD patients, monoclonal antibodies, LY2928057 and LY3113593, targeting ferroportin and BMP6 respectively, were tested in CKD patients...
January 24, 2019: British Journal of Clinical Pharmacology
(no author information available yet)
No abstract text is available yet for this article.
January 14, 2019: New England Journal of Medicine
Gregg L Semenza
Hypoxia-inducible factors (HIFs) control transcriptional responses to reduced O2 availability. HIFs are heterodimeric proteins composed of an O2 -regulated HIF-α subunit and a constitutively expressed HIF-1β subunit. HIF-α subunits are subject to prolyl hydroxylation, which targets the proteins for degradation under normoxic conditions. Small molecule prolyl hydroxylase inhibitors, which stabilize the HIF-α subunits and increase HIF-dependent expression of erythropoietin, are in phase III clinical trials for the treatment of anemia in patients with chronic kidney disease...
January 6, 2019: Annual Review of Pharmacology and Toxicology
Sanne Eg van Raaij, Alexander J Rennings, Bart J Biemond, Saskia Em Schols, Erwin Tg Wiegerinck, Hennie Mj Roelofs, Ewout J Hoorn, Stephen B Walsh, Tom Nijenhuis, Dorine W Swinkels, Rachel Van Swelm
BACKGROUND: In physiological conditions, circulating iron can be filtered by the glomerulus and is almost completely reabsorbed by the tubular epithelium to prevent urinary iron wasting. Increased urinary iron concentrations have been associated with renal injury. However, it is not clear whether increased urinary iron concentrations in patients are the result of increased glomerular iron filtration and/or insufficient tubular iron reabsorption and if these processes contribute to renal injury...
January 9, 2019: American Journal of Physiology. Renal Physiology
Steven Fishbane, Daniel W Ross, Susana Hong
No abstract text is available yet for this article.
January 4, 2019: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
Maciej Drozdz, André Weigert, Fatima Silva, João Frazão, Abdulkareem Alsuwaida, Mahesh Krishnan, Werner Kleophas, Szymon Brzosko, Fredrik K Johansson, Stefan H Jacobson
BACKGROUND: The optimal treatment algorithm for iron therapy and the use of erythropoiesis-stimulating agents (ESA) in anemic hemodialysis (HD) patients has not been established. Hemoglobin (Hb) target levels can be achieved through more frequent intravenous (IV) iron use with lower ESA dose, or with less iron dosing but higher ESA. ESA therapy to correct anemia may result in severe arterial and venous thrombotic complications and the evidence base evaluating hard clinical outcomes related to the use of IV iron is sparse...
January 7, 2019: BMC Nephrology
2019-01-10 09:56:15
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