A biomathematical model of human erythropoiesis and iron metabolism

Abstract

Anaemia therapy or perisurgical support of erythropoiesis often require both, EPO and iron medication. However, excessive iron medication can result in iron overload and it is challenging to control haemoglobin levels in a desired range. To support this task, we develop a biomathematical model to simulate EPO- and iron medication in humans. We combine our previously established model of human erythropoiesis including comprehensive pharmacokinetic models of EPO applications with a newly developed model of iron metabolism including iron supplementation. Equations were derived by translating known biological mechanisms into ordinary differential equations. Qualitative model behaviour is studied in detail considering a variety of interventions such as bleeding, iron malnutrition and medication. The model can explain time courses of erythrocytes, reticulocytes, haemoglobin, haematocrit, red blood cells, EPO, serum iron, ferritin, transferrin saturation, and transferrin under a variety of scenarios including EPO and iron application into healthy volunteers or chemotherapy patients. Unknown model parameters were determined by fitting the predictions of the model to time series data from literature. We demonstrate how the model can be used to make predictions of untested therapy options such as cytotoxic chemotherapy supported by iron and EPO. Following our ultimate goal of establishing a model of anaemia treatment in chronic kidney disease, we aim at translating our model to this pathological condition in the near future.