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Abstract: SA-PO249

Hemoglobin Cycling Induced by Delayed Patient-Therapy Feedback During ESA Treatment

Session Information

Category: Anemia and Iron Metabolism

  • 202 Anemia and Iron Metabolism: Clinical

Authors

  • Joerg, David J., Fresenius Medical Care, Bad Homburg, Germany
  • Fuertinger, Doris H., Fresenius Medical Care, Bad Homburg, Germany
  • Kotanko, Peter, Renal Research Institute , New York, New York, United States
Background

Chronic kidney disease (CKD) commonly entails anemia, leading to poor patient outcomes. During treatment of anemia with erythropoiesis-stimulating agents (ESAs), patients frequently experience hemoglobin (Hgb) “cycling” periods during which the patient’s Hgb levels periodically over- and undershoot a defined target range of 10–11.5 g/dL. Using a computational model of anemia treatment (“Virtual Anemia Trial”; Fuertinger et al., CPT Syst. Pharmacol. 7(4) 219, 2018), we aimed to detect treatment-related causes of this behavior.

Methods

We carried out Virtual Anemia Trials with 6659 virtual patients (“avatars”) under 4 different anemia treatment protocols (a to d) for one simulated year of treatment. Avatars differed in endogenous EPO levels, total blood volume, and ESA half-life. Treatment protocols differed in ESA dosing charts (steps between doses and administration frequency) and the criteria that determine ESA dose recommendations based on the patient’s Hgb history (i.e., critical Hgb levels and/or rates of change).

Results

The 4 treatment protocols yielded different distributions of Hgb amplitudes (difference between maximum and minimum Hgb in the second half of the simulated patient year), with mean ± s.d. given by (a) 1.7 ± 1.5 g/dL, (b) 1.7 ± 1.4 g/dL, (c) 1.6 ± 1.3 g/dL and (d) 1.1 ± 1.0 g/dL, respectively (see Figure). Except for (a) vs. (b), differences between the corresponding distributions were statistically significant when pairwise compared (Pearson chi-squared test; p < 0.05).

Conclusion

Our results suggest that certain treatment protocols can augment Hgb cycling instead of preventing it. Analysis of the differences between probed treatment protocols reveals two treatment-related causes for Hgb cycling: (i) too late ESA dose changes in response to falling/rising Hgb levels and (ii) too extreme dosing decisions (e.g., a complete ESA hold for a too long time) that prevent Hgb levels from remaining within target after transiently reaching it. Based on these insights, existing treatment protocols may be modified to reduce patients’ Hgb cycling.

Funding

  • Commercial Support