Abstract
Anemia commonly occurs in people with chronic kidney disease (CKD) and is associated with poor clinical outcomes. The management of patients with anemia in CKD is challenging, due to its severity, frequent hypo-responsiveness to treatment with erythropoiesis stimulating agents (ESA) and common hemoglobin cycling. Nonlinear dose-response curves and long delays in the effect of treatment on red blood cell population size complicate predictions of hemoglobin (Hgb) levels in individual patients. A comprehensive physiology based mathematical model for erythropoiesis was adapted individually to 60 hemodialysis patients treated with ESAs by identifying physiologically meaningful key model parameters from temporal Hgb data. Crit-Line® III monitors provided non-invasive Hgb measurements for every hemodialysis treatment. We used Hgb data during a 150-day baseline period together to estimate a patient’s individual red blood cell lifespan, effects of the ESA on proliferation of red cell progenitor cells, endogenous erythropoietin production and ESA half-life. Estimated patient specific parameters showed excellent alignment with previously conducted clinical studies in hemodialysis patients. Further, the model qualitatively and quantitatively reflected empirical hemoglobin dynamics in demographically, anthropometrically and clinically diverse patients and accurately predicted the Hgb response to ESA therapy in individual patients for up to 21 weeks. The findings suggest that estimated model parameters can be used as a proxy for parameters that are clinically very difficult to quantify. The presented method has the potential to provide new insights into the individual pathophysiology of renal anemia and its association with clinical outcomes and can potentially be used to guide personalized anemia treatment.
Highlights
A decrease in the total amount of red blood cells (RBC) and hemoglobin (Hgb) levels impairing the blood’s ability to carry oxygen is referred to as anemia
In 2014, 84% of 680,000 end-stage renal disease patients in the US were treated for anemia by administering erythropoiesis stimulating agents (ESA) [1]
A comprehensive physiologically informed mathematical model of erythropoiesis was adapted to 60 chronic HD patients using parameter estimation techniques
Summary
A decrease in the total amount of red blood cells (RBC) and hemoglobin (Hgb) levels impairing the blood’s ability to carry oxygen is referred to as anemia. The administration of ESAs exerts hematological effects similar to the endogenous hormone erythropoietin (EPO) which drives the production of new RBCs. Based on several randomized controlled trials the most current clinical practice guideline calls for a partial correction of anemia in CKD patients, urging inception of therapy at a Hgb of 9.0 to 10.0 g/dl, and treatment to levels in general not beyond 11.5 g/dl [2]. A later study, which was inspired by [5], focused on an application to periodic hematological diseases [8] and Crauste and colleagues [9,10,11] presented a different modification of the Belair model incorporating self-renewal of progenitor cells. Comprehensive physiology based models are commonly used to generate insights and test hypotheses about underlying mechanisms of diseases Individually estimated parameters that are of physiological key importance allow further insight into patient specific pathophysiology
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
