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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: The results showed that chronic conditions and multiple chronic conditions are prevalent in older adults across Florida and the United States. Even though slight differences were observed, the similar estimates of prevalence of chronic conditions and multiple chronic conditions across OneFlorida and HCUP NIS suggested that clinical research data networks such as OneFlorida, built from heterogeneous data sources, can provide rich data resources for conducting large-scale secondary data analyses.
Source: Journal of Medical Internet Research - Category: General Medicine Authors: Source Type: research
Publication date: Available online 11 April 2018 Source:Journal of the Formosan Medical Association Author(s): 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 t...
Source: Journal of the Formosan Medical Association - Category: General Medicine Source Type: research
Abstract 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. When anemia or hypoxia occurs, transcriptional factor, hypoxia...
Source: J Formos Med Assoc - Category: General Medicine Authors: Tags: J Formos Med Assoc Source Type: research
Majid A Almadi, Othman Alharbi, Nahla Azzam, Mohannad Altayeb, Salem Thaniah, Abdulrahman AljebreenSaudi Journal of Gastroenterology 2018 24(2):93-99 Background/Aims: Optimal bowel preparation is essential for a complete high-quality colonoscopy. We sought to determine whether an inpatient, as opposed to an ambulatory setting, would affect the quality of bowel preparation. Patients and Methods: A retrospective chart review was conducted in a tertiary care university hospital. We collected demographic data from consecutive patients who underwent a colonoscopy for any reason between August 2007 and April 2012. Results: ...
Source: The Saudi Journal of Gastroenterology - Category: Gastroenterology Authors: Source Type: research
Abstract 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. This review will provide...
Source: Seminars in Dialysis - Category: Urology & Nephrology Authors: Tags: Semin Dial Source Type: research
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. How...
Source: BMC Complementary and Alternative Medicine - Category: Complementary Medicine Authors: Tags: Research article Source Type: research
Chronic kidney disease (CKD) affects approximately 15 to 30% of geriatric cats. The role of inflammation in this disease is not well characterized. In human patients, chronic inflammation and oxidative stress play key roles in the development and progression of CKD. Increased concentrations of positive acute-phase proteins (APPs), such as C-reactive protein(CRP) and inflammatory cytokines, such as interleukin (IL)-6, have been described in humans with CKD and are associated with poor outcome. Anemia also is considered a negative prognostic factor in humans with renal failure, and evidence suggests that the severity of anem...
Source: Advances in Small Animal Medicine and Surgery - Category: Veterinary Research Tags: Nephrology/Urology Source Type: research
American Journal of Hematology, EarlyView.
Source: American Journal of Hematology - Category: Hematology Source Type: research
Conclusions Blood 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
by Laura M. Raffield, Jacob C. Ulirsch, Rakhi P. Naik, Samuel Lessard, Robert E. Handsaker, Deepti Jain, Hyun M. Kang, Nathan Pankratz, Paul L. Auer, Erik L. Bao, Joshua D. Smith, Leslie A. Lange, Ethan M. Lange, Yun Li, Timothy A. Thornton, Bessie A. Young, Goncalo R. Abecasis, Cathy C. Laurie, Deborah A. Nickerson, Steven A. McCarroll, Adolfo Correa, James G. Wilson, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Hematology&Hemostasis, Diabetes, and Structural Variation TOPMed Working Groups , Guillaume Lettre, Vijay G. Sankaran, Alex P. Reiner Co-inheritance of α-thalassemia has a significant p...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research
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