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 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.
Competing Interests: 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.
(Copyright: © 2023 Jörg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)