Whole-body iron transport and metabolism: Mechanistic, multi-scale model to improve treatment of anemia in chronic kidney disease

by 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 er ythropoietin 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.g., CKD) and trea tment are unknown. Unwanted iron accumulation in patients is known to lead to adverse effects. Current whole-body models lack the mechanistic details of iron transport related to RBC maturation, transferrin (Tf and TfR) dynamics and assume passive iron efflux from macrophages. Hence, they are not pr edictive of whole-body iron dynamics and cannot be used to design individualized patient treatment. For prediction, we developed a mechanistic, multi-scale computational model of whole-body iron metabolism incorporating four compartments containing major pools of iron and RBC generation process. The model accounts for multiple forms of ironin vivo, mechanisms involved in iron uptake and release and their regulation. Furthermore, the model is interfaced with drug pharmacokinetics to allow simulation of treatment dynamics. We calibrated our m...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research

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Conclusions: This is the first Italian prospective study performed with a large cohort of CKD patients over a 3-year period. Considering the multifactorial burden of diseases associated with CKD patients, the need for greater attention to CKD and related disorders is paramount.Nephron
Source: Nephron - Category: Urology & Nephrology Source Type: research
Abstract OBJECTIVE: Systemic sclerosis (SSc) is a disease of autoimmunity, fibrosis, and vasculopathy. Scleroderma renal crisis (SRC) is one of the most severe complications. Corticosteroid exposure, presence of anti-RNA polymerase III antibodies (ARA), skin thickness, and significant tendon friction rubs are among the known risk factors at SSc diagnosis for developing future SRC. Identification of additional clinical characteristics and laboratory findings could expand and improve the risk profile for future SRC at SSc diagnosis. METHODS: In this retrospective cohort study of the entire military electronic m...
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ConclusionsBlood T1 estimation method can confound the interpretation of CBF changes measured using ASL MRI in patients with CKD. Blood T1 should ideally be corrected for hematocrit effects in clinical populations with anemia.
Source: Journal of Neuroradiology - Category: Radiology Source Type: research
Publication date: Available online 11 April 2018Source: Journal of the Formosan Medical AssociationAuthor(s): Hong-Mou Shih, Chih-Jen Wu, Shuei-Liong LinAnemia 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...
Source: Journal of the Formosan Medical Association - Category: General Medicine Source Type: research
Publication date: Available online 22 May 2018Source: Diabetes &Metabolic Syndrome: Clinical Research &ReviewsAuthor(s): Nicolas Roberto Robles, Juan Lucio Ramos, Edgar Chavez, Boris Gonzalez Candia, Miguel Angel Bayo, Antonio Cidoncha, Juan Lopez Gomez, Juan Jose CuberoAbstractBackgroundsIron deficiency has been studied extensively in patients with chronic kidney disease on hemodialysis therapy. However, few studies looked at iron treatment in the non-dialysis chronic kidney disease population.MethodsFive hundred and eighty patients were studied (247 were diabetic persons). Patients were divided into 4 groups: non...
Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews - Category: Endocrinology Source Type: research
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Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Diabetic Medicine,Volume 0, Issue ja, -Not available-.
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Authors: Del Vecchio L, Locatelli F Abstract INTRODUCTION: In the last decade, concerns have been raised around the use of erythropoiesis stimulating agents (ESA) and intravenous iron in CKD patients, especially when given at high doses. Moreover, treatment with ESA is expensive. Areas covered: We searched PubMed for original articles, reviews and editorials having as a topic anaemia, chronic kidney disease, hypoxia inducible factor, hepcidin, iron, hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI). HIF-PHI are a new class of small molecules activating HIF-alfa isoforms (the main mediators of the eff...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research
ConclusionsBlood T1 estimation method can confound the interpretation of CBF changes measured using ASL MRI in patients with CKD. Blood T1 should ideally be corrected for hematocrit effects in clinical populations with anemia.
Source: Journal of Neuroradiology - Category: Radiology Source Type: research
Publication date: Available online 11 April 2018Source: Journal of the Formosan Medical AssociationAuthor(s): Hong-Mou Shih, Chih-Jen Wu, Shuei-Liong LinAnemia 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...
Source: Journal of the Formosan Medical Association - Category: General Medicine Source Type: research
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