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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Authors: Hamed SA Abstract INTRODUCTION: Uremic syndrome of chronic kidney disease (CKD) is a term used to describe clinical, metabolic and hormonal abnormalities associated with progressive kidney failure. It is a rapidly growing public health problem worldwide. Nervous system complications occur in every patient with uremic syndrome of CKD. Areas covered: This review summarized central and peripheral nervous system complications of uremic syndrome of CKD and their pathogenic mechanisms. They include cognitive deterioration, encephalopathy, seizures, asterixis, myoclonus, restless leg syndrome, central pontine mye...
Source: Expert Review of Clinical Pharmacology - Category: Drugs & Pharmacology Tags: Expert Rev Clin Pharmacol Source Type: research
Conclusion: Patients with CKD had more often permanent type of AF. Percutaneous interventions of the left main coronary artery, the only elective procedures influencing patients ’ prognosis, were done more frequently in CKD patients with AF. In-hospital mortality was significantly higher in patients with severe renal impairment. Despite the higher risk of ischaemic stroke in CKD group the use of oral anticoagulation therapy was significantly less frequent and the patients were deprived of the confirmed benefits of such treatment.Kidney Blood Press Res 2018;43:1796 –1805
Source: Kidney and Blood Pressure Research - Category: Urology & Nephrology Source Type: research
In this study, we sought to better understand the characteristics, treatment, and outcomes of older patients with MM.Methods: We identified all patients diagnosed with MM at age 80 or older in the Surveillance, Epidemiology, and End Results Program (SEER) database from 2007-2013 to determine incidence and outcomes. Subset analysis was then performed on patients included in the SEER-Medicare linked database who were enrolled in Medicare Parts A, B, and D to further explore patient characteristics and treatment patterns.Results: The incidence of MM increases over age, peaking after age 80. The annual incidence for those aged...
Source: Blood - Category: Hematology Authors: Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research
ConclusionMGUS is often incidentally detected as part of a work up for other medical conditions, and our results reveal that there is a variety of reasons for which monoclonal testing is performed. With recent developments in our understanding of the significance of monoclonal gammopathy and its association with certain renal and organ damage (Fermand et al., 2018; Leung et al., 2012), there may be a change in how the paraproteinemia investigations are utilized by clinicians in different disciplines. It will be important to recognize and establish appropriate indications for testing. Furthermore, MGUS patients present with...
Source: Blood - Category: Hematology Authors: Tags: 651. Myeloma: Biology and Pathophysiology, excluding Therapy: Poster III Source Type: research
Introduction: MGUS is generally an incidental finding in the diagnostic work-up for clinical signs and symptoms suggestive of lymphoplasmacytic malignancies (multiple myeloma, light chain amyloidosis, and Waldenström macroglobulinemia), which are relatively rare (
Source: Blood - Category: Hematology Authors: Tags: 901. Health Services Research-Non-Malignant Conditions: Poster I Source Type: research
IntroductionIron deficiency anemia (IDA) is the leading cause of anemia in the United States. Although oral iron formulations can correct IDA, they are generally poorly tolerated due to gastrointestinal side effects and may require long term use to maintain normal hemoglobin. Intravenous iron is an alternative to oral iron especially in adults who cannot tolerate or absorb oral iron. Intravenous iron preparations avoid problems of malabsorption and can quickly correct IDA but little data exists on the safety or efficacy in patients without chronic kidney disease (CKD) with or without dialysis, heart failure, uterine bleedi...
Source: Blood - Category: Hematology Authors: Tags: 901. Health Services Research-Non-Malignant Conditions Source Type: research
BackgroundSickle cell disease (SCD) is a monogenetic disorder, with 300,000 to 400,000 infants born annually with the disease around the world (Kato et al, Nat Rev Dis Primers 2018). SCD is a progressively debilitating and life-threatening disease characterized by hemolytic anemia, painful vaso-occlusive events (VOEs) and persistent vasculopathy that result in significant morbidity, poor quality of life and early mortality. There is significant heterogeneity in clinical manifestations of SCD, given that vaso-occlusion and hemolysis-associated endothelial dysfunction may manifest in any tissue or organ. Severely affected pa...
Source: Blood - Category: Hematology Authors: Tags: 903. Outcomes Research-Non-Malignant Hematology: Poster III Source Type: research
Introduction: Pediatric patients with Sickle Cell Anemia (SCA) are at risk for developing albuminuria. Hyperfiltration precedes the development of albuminuria in patients with diabetes but the natural history of hyperfiltration on the progression to albuminuria has not been studied in children with SCA.Methods: We have enrolled 185 participants with HbSS or SB0 thalassemia in a prospective pediatric cohort study evaluating progression to chronic kidney disease; the mean current age of participants in this cohort is 14 years. We have abstracted 817 urine microalbumin creatinine measurements and 891 estimations of GFR (eGFR)...
Source: Blood - Category: Hematology Authors: Tags: 114. Hemoglobinopathies, Excluding Thalassemia-Clinical: Organ Damage and Clinical Complications in Sickle Cell Disease Source Type: research
IntroductionBased on improvement of overall survival (OS), lenalidomide (R) maintenance after up-front autologous stem cell transplantation has recently been approved for multiple myeloma (MM) patients (pts). Conversely, in transplant non-eligible (TNE) pts R maintenance after R-based induction improved progression free survival (PFS) but had no impact on OS. First-line treatment with VMP is considered a standard of care for newly diagnosed (ND) TNE pts, but whether maintenance therapy with R after VMP induction can further improve PFS and OS is currently unknown.AimsThe prospective phase IIb GERMAIN trial (EudraCT-No: 201...
Source: Blood - Category: Hematology Authors: Tags: 653. Myeloma: Therapy, excluding Transplantation: Poster I Source Type: research
The objective of this analysis was to assess the importance of parenteral iron dosing on serum hemoglobin (Hgb) level normalization in real world clinical practice.MethodsData was obtained from the Decision Resources Group (DRG) Real World Evidence Data Repository US database, which includes medical and pharmacy claims, and electronic health record data representing more than 300 million patient lives. Adult patients (≥18 years of age) who were treated with parenteral iron between 3/1/2015 and 2/28/2017 were included in the analysis. Eligible patients were required to have their most recent baseline Hgb level below normal (Hgb
Source: Blood - Category: Hematology Authors: Tags: 903. Outcomes Research-Non-Malignant Hematology: Poster I Source Type: research
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