Reducing versus Discontinuing Erythropoietin at High Hemoglobin Levels

Abstract

A 2006 change in Medicare policy allowed reimbursement for erythropoietin (EPO) in dialysis patients whose most recent hemoglobin exceeded 13 g/dl. We investigated the effects of a change in dosing algorithm implemented in response to this policy, in which EPO dosages were reduced instead of temporarily discontinued for hemoglobin levels Ն13 g/dl. Among 1688 individuals in 18 hemodialysis units, the reduction protocol resulted in more hemoglobin levels Ն13 g/dl (P Ͻ 0.0001), fewer levels between 11 and 12.9 g/dl (P Յ 0.004), no difference in the proportion of levels Ͻ11 g/dl, and more EPO administered per session (P Ͻ 0.0001) than the discontinuation protocol. In view of the expense of erythropoiesis stimulating agents and the uncertainty of the safety of using EPO to achieve high hemoglobin targets, this study suggests that discontinuation, rather than reduction, of EPO treatment is appropriate when hemoglobin reaches 13 g/dl in hemodialysis patients.

Nadir Hemoglobin Levels after Discontinuation of Epoetin in Hemodialysis Patients

“…Similarly, Ebben et al (14) found an association between hemoglobin variability and the number of comorbid conditions. This study expands on a prior analysis by our group that showed a benefit on a dialysis provider level associated with discontinuation of epoetin at higher levels (20). In that study, there was no significant difference in the number of patients with a hemoglobin level Ͻ10 g/dl in any given month, whereas in this study, the discontinuation protocol was associated with significantly more patients with low nadir hemoglobin levels.…”

“…A prior cross-sectional analysis by our group using Dialysis Clinic Inc (DCI) data showed that reduction versus discontinuation of epoetin at a hemoglobin level of 13 g/dl resulted in significantly more hemoglobin levels Ͼ13 g/dl, fewer levels between 11 and 12.9 g/dl, and no difference in the proportion of levels Ͻ11 g/dl each month (20). This study builds on this observation by evaluating longitudinal changes in hemoglobin levels in individual hemodialysis patients with hemoglobin Ն 13 g/dl treated with reduction or discontinuation of epoetin to help inform best management of high hemoglobin levels in these individuals.…”

Epo and Non-hematopoietic Cells: What Do We Know?

“…Safety concerns were raised during treatment of anemia in diabetic patients with CKD when they showed a twofold higher risk of stroke, an increased risk of venous thromboembolism and cancer-related deaths (210). Several studies have suggested that exposure to high doses of Epo mimetics, when needed to achieve higher hemoglobin levels, is harmful and explains this phenomenon (211,212). Very high doses of Epo, in conjunction with hypoxia, has also been associated with a paradoxical neurotoxic effect suggesting dose-response conditions need to be optimized.…”

Hemoglobin Variability in Anemia of Chronic Kidney Disease

“…Selecting and administrating an ESA and adjusting its dosing, whether initiated by a physician on the basis of clinical judgment or whether used through clinical decision algorithms by nonphysician health care providers, should follow the principles of a "negative-feedback loop." 21 Setting a narrow hemoglobin target of 11 to 12 g/dl may increase the More frequent hemoglobin monitoring (e.g., weekly to biweekly rather than monthly) Shortening of the time lapse between the blood draw and result review by the nephrologist or other anemia management providers Fine-tuned (rather than drastic) changes in ESA dosage (e.g., 25% change in the ESA and/or iron dosage rather than doubling the dosage or withholding the ESA a ) Preemptive adjustment of the ESA dosage for temporal trends that are still within the target range (e.g., dosage reduction ͓or increase͔ by 25% with upward ͓or downward͔ trends a ) Switch to different types of ESA (e.g., longer acting ESA for noncompliant patients with frequent missing of dialysis treatments) Preemptive increase in ESA dosage during infectious or inflammatory conditions or bleeding (e.g., dialysis access surgeries, heavy menstruations) or immediately after a hospitalization Prompt and effective treatment of infection and inflammation in ESA-hyporesponsive patients Optimal management of hyperparathyroidism including appropriate use of vitamin D analogs, calcimimetics, and phosphorus binders Maintenance iron supplementation during ESA treatment (e.g., weekly to monthly low-dosage intravenous iron b ) Avoidance of iron-ESA dosage discrepancy (e.g., high ESA dosage with little or no iron and vice versa) Adequate attention to and appropriate interpretation of iron markers Timely workup of persistent ESA hyporesponsiveness or erythrocytosis for prompt detection and management gastrointestinal or other types bleeding or malignancies associated with internal ESA production Implementing strategies to improve patient compliance with dialysis treatment attendance Development and ongoing improvement of facility-specific algorithms for anemia management tailored to the need of the regional population Considering novel computerized intelligent methods to model the hemoglobin variability across patients and clinics a Transient withholding ESA/iron (e.g., for Ն1 wk) for hemoglobin values Ͼ13 g/dl range 71 or doubling the dosage for hemoglobin values below 9 to 10 g/dl may also be considered. b More concrete examples include once a week administration of 25 to 50 mg of iron sucrose or dextran, 31.0 to 62.5 mg of iron gluconate, or similar dosages for ferumoxytol and other intravenous iron agents.…”