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'...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1010850 |
| _version_ | 1811176409685557248 |
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| author | David J Jörg Doris H Fuertinger Peter Kotanko |
| author_facet | David J Jörg Doris H Fuertinger Peter Kotanko |
| author_sort | David J Jörg |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T19:52:07Z |
| format | Article |
| id | doaj.art-ccb441708a584dfbbe2497350d0b8f40 |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-04-10T19:52:07Z |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-ccb441708a584dfbbe2497350d0b8f402023-01-28T05:30:29ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582023-01-01191e101085010.1371/journal.pcbi.1010850Mechanisms of hemoglobin cycling in anemia patients treated with erythropoiesis-stimulating agents.David J JörgDoris H FuertingerPeter KotankoPatients 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.https://doi.org/10.1371/journal.pcbi.1010850 |
| spellingShingle | David J Jörg Doris H Fuertinger Peter Kotanko Mechanisms of hemoglobin cycling in anemia patients treated with erythropoiesis-stimulating agents. PLoS Computational Biology |
| title | Mechanisms of hemoglobin cycling in anemia patients treated with erythropoiesis-stimulating agents. |
| title_full | Mechanisms of hemoglobin cycling in anemia patients treated with erythropoiesis-stimulating agents. |
| title_fullStr | Mechanisms of hemoglobin cycling in anemia patients treated with erythropoiesis-stimulating agents. |
| title_full_unstemmed | Mechanisms of hemoglobin cycling in anemia patients treated with erythropoiesis-stimulating agents. |
| title_short | Mechanisms of hemoglobin cycling in anemia patients treated with erythropoiesis-stimulating agents. |
| title_sort | mechanisms of hemoglobin cycling in anemia patients treated with erythropoiesis stimulating agents |
| url | https://doi.org/10.1371/journal.pcbi.1010850 |
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