Original article
Biomedical System Dynamics to Improve Anemia Control With Darbepoetin Alfa in Long-Term Hemodialysis Patients

https://doi.org/10.1016/j.mayocp.2013.10.022Get rights and content

Abstract

Objective

To determine the value of a biomedical system dynamics (BMSD) approach for optimization of anemia management in long-term hemodialysis patients because elevated hemoglobin levels and high doses of erythropoiesis-stimulating agents (ESAs) may negatively affect survival in this population.

Patients and Methods

A model of erythropoiesis and its response to ESAs on the basis of a BMSD method (Mayo Clinic Anemia Management System [MCAMS]) was developed. Thereafter, an open-label, prospective, nonrandomized practice quality improvement project was performed with retrospective analysis in 8 community-based outpatient hemodialysis facilities. All prevalent hemodialysis patients seen from January 1, 2007, through December 31, 2010 (300-342 patients per month), were included with darbepoetin as the ESA. The primary outcome was the percentage of patients who attained the desired hemoglobin level. Secondary outcome measures included the percentage of patients with hemoglobin values above the desired range and mean dose of darbepoetin used.

Results

The 3 treatment periods were (1) standard ESA protocol in 2007, (2) transition to the MCAMS (2008 to June 2009), and (3) stability period with the MCAMS used in all hemodialysis facilities (2009 to 2010). In the first 6 months of 2007, 69% of patients were in the desired range and 26% were above the range. In comparison, during the first 5 months of 2010, 83% were in and 6% were above the range (P<.001). The mean monthly darbepoetin dose per patient decreased from 304 μg in 2007 to 173 μg by the second half of 2009 (P<.001).

Conclusion

With the introduction of the MCAMS, more patients had hemoglobin levels in the desired range and fewer patients exceeded the target range, with a concomitant 40% reduction in darbepoetin use.

Section snippets

Mayo Clinic Dialysis System

The Mayo Clinic Dialysis System (MCDS) includes 8 outpatient dialysis facilities (identified as A through H) with a census of 8 to 93 prevalent patients in each facility (300-342 patients). We included all prevalent patients who received at least one hemodialysis treatment and had at least one hemoglobin determination in each respective month. There were no changes in our target goals for dialysis adequacy (single-pool Kt/V >1.60) or other practices that might have knowingly affected anemia

Patient Demographic Characteristics

The prevalent hemodialysis population in January of each of the years 2007 through 2010 was analyzed to ascertain stable demographic characteristics. The patients' mean ± SD age (69.3±16.0 years in 2007; P=.18 among all 4 years), race (88% white), diabetic nephropathy prevalence (45%-48%), diabetes mellitus prevalence (54%-57%), and mean ± SD years of dialysis (2.7±2.9 years in 2007; P=.56 among all 4 years) did not change significantly.

Hemoglobin Values

The monthly distribution of hemoglobin values for all

Discussion

Management of anemia in hemodialysis patients is complex because of the delayed and prolonged effect of ESAs on erythrocyte production, the effect of hemodialysis and inflammation on erythrocyte survival and ESA responsiveness, hemodialysis-related blood loss, and other factors. These dynamic factors differ in patients and are not accounted for in most ESA administration protocols. In 2007, similar to most hemodialysis facilities, we used an anemia management protocol consistent with the

Conclusion

To our knowledge, we describe the first long-term use of the BMSD method for anemia management in a large number of long-term hemodialysis patients. When compared with a prior ESA algorithm-based protocol that is similar to those used by most dialysis facilities, the MCAMS was associated with substantially fewer patients with higher hemoglobin values, more patients with hemoglobin values in the desired range, a 40% to 50% reduction in ESA use, and less variation in hemoglobin values. The BMSD

Acknowledgments

We acknowledge all of the physicians, nurse practitioners, physician assistants, nurses, and administrative staff in the Mayo Clinic Dialysis System for their cooperation and support during implementation of this new system. The Advance Management Group also acknowledges the important support and contributions of T. Ronald Chrisope, Mark Diez, Karl J. Rogers, and Steven L. Todd.

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    Grant Support: The statistical analysis was funded by the Mayo Clinic Division of Nephrology and Hypertension. No extramural funds or grants were used to fund this analysis. Dr Dingli acknowledges support from the Minnesota Partnership for Biotechnology and Medical Genomics and Mayo Clinic.

    Potential Competing Interests: Drs McCarthy, Albright, Gallaher, Steensma, and Dingli, Messrs Hocum, Gudgell, and Rogers, and the Mayo Clinic stand to receive royalties related to any commercial development of the MCAMS.

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    Copyright © 2014 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.