Mechanisms of hemoglobin cycling in anemia patients treated with erythropoiesis-stimulating agents

Patients with renal anemia are frequently treated with erythropoiesis-stimulating agents (ESAs), which are dynamically dosed in order to stabilize blood hemoglobin levels within a specified target range. During typical ESA treatments, a fraction of patients experience hemoglobin ‘cycling’ periods du...

Full description

Saved in:
Bibliographic Details
Published inPLoS computational biology Vol. 19; no. 1; p. e1010850
Main Authors Jörg, David J., Fuertinger, Doris H., Kotanko, Peter
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 24.01.2023
Public Library of Science (PLoS)
Subjects
Algorithms
Anemia
Anemia - drug therapy
Apoptosis
Biology and Life Sciences
Blood
Bone marrow
Care and treatment
Cell cycle
Control theory
Cycles
Decision trees
Dosage
Erythrocytes
Erythropoiesis
Feedback
Hematinics - adverse effects
Hematinics - therapeutic use
Hemoglobin
Hemoglobin synthesis
Hemoglobins
Humans
Kidney Diseases
Life span
Medicine and Health Sciences
Patient outcomes
Patients
Physiological effects
Physiological factors
Physiology
Renal anemia
Research and Analysis Methods
Germany
Online AccessGet full text

Cover

More Information
Summary:Patients with renal anemia are frequently treated with erythropoiesis-stimulating agents (ESAs), which are dynamically dosed in order to stabilize blood hemoglobin levels within a specified target range. During typical ESA treatments, a fraction of patients experience hemoglobin ‘cycling’ periods during which hemoglobin levels periodically over- and undershoot the target range. Here we report a specific mechanism of hemoglobin cycling, whereby cycles emerge from the patient’s delayed physiological response to ESAs and concurrent ESA dose adjustments. We introduce a minimal theoretical model that can explain dynamic hallmarks of observed hemoglobin cycling events in clinical time series and elucidates how physiological factors (such as red blood cell lifespan and ESA responsiveness) and treatment-related factors (such as dosing schemes) affect cycling. These results show that in general, hemoglobin cycling cannot be attributed to patient physiology or ESA treatment alone but emerges through an interplay of both, with consequences for the design of ESA treatment strategies.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
I have read the journal’s policy and the authors of this manuscript have the following competing interests: DJJ and DHF are employees of Fresenius Medical Care Germany. PK is an employee of the Renal Research Institute, a wholly owned subsidiary of Fresenius Medical Care. PK receives author royalties from HSTalks and holds stock in Fresenius Medical Care. PK is on the Editorial Board of Blood Purification, Kidney and Blood Pressure Research, and Frontiers in Nephrology. PK is inventor on multiple patents in the field of kidney medicine.
ISSN:1553-7358
1553-734X
1553-7358
DOI:10.1371/journal.pcbi.1010850