Kidney Week

Abstract: SA-PO220

Patient-Specific Characteristics of Erythropoiesis and Their Influence on Hemoglobin Stability

Session Information

• Anemia and Iron Metabolism: Basic
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Anemia and Iron Metabolism

• 201 Anemia and Iron Metabolism: Basic

Authors

• Fuertinger, Doris H., Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany

Doris H. Fuertinger,

• Fuertinger, Stefan, Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Frankfurt am Main, Germany

Stefan Fuertinger,

• Cherif, Alhaji, Renal Research Institute , New York, New York, United States

Alhaji Cherif,

• Rogg, Sabrina, Fresenius Medical Care Deutschland GmbH, Bad Homburg, Germany

Sabrina Rogg,

• Kotanko, Peter, Renal Research Institute , New York, New York, United States

Peter Kotanko,

Background

In hemodialysis (HD) patients treated with erythropoiesis-stimulating agents (ESA) maintaining hemoglobin (Hgb) levels within recommended ranges is difficult. Many patients express Hgb excursions above and below the target range over the course of a year. This Hgb variability is associated with clinical events and ESA dose changes. This study investigates differences in biological key characteristics of erythropoiesis in HD patients and its influence on Hgb stability.

Methods

We adapted a comprehensive mathematical model of erythropoiesis to individual HD patients treated with methoxy polyethylene glycol-epoetin beta to estimate key characteristics of their red blood cell (RBC) reproduction cycles (Fuertinger, Plos One 2018), including RBC lifespan, endogenous EPO levels, ESA half-life and ESA influence on apoptosis and maturation velocity of RBC progenitors. In-silico tests were performed to distinguish Hgb “cyclers” from “non-cyclers” (criteria per Fishbane & Berns, Kidney Int. 2005). Estimated physiological parameters are depicted as violin plots, groups are compared by t-test.

Results

We estimated patient-specific characteristics of erythropoiesis in 6659 HD patients (♀: 46 %, Black: 43 %, mean ± SD: age 64 ± 14 years, BMI: 29.4 ± 7.6 kg/m²). 29.8% were categorized as Hgb cyclers. Figure 1 compares erythropoiesis characteristics between cyclers and non-cyclers. We observed a statistically significant difference between Hgb cyclers and non-cyclers in RBC lifespan (mean±SD: 72±18 vs 78±21 days), endogenous EPO levels (13±6 vs 18±8 U/l), ESA half-life (159±46 vs 115±57 hours) and anti-apoptotic effects.

Conclusion

Patient-specific parameter estimates suggest that certain underlying biological characteristics may predispose patients to Hgb cycling. A better understanding of these effects could permit tailoring anemia algorithms to this subgroup to improve their Hgb variability and eventually clinical outcomes.