Individualized Anemia Management Reduces Hemoglobin Variability in Hemodialysis Patients

One-size-fits-all protocol-based approaches to anemia management with erythropoiesis-stimulating agents (ESAs) may result in undesired patterns of hemoglobin variability. In this single-center, double-blind, randomized controlled trial, we tested the hypothesis that individualized dosing of ESA improves hemoglobin variability over a standard population-based approach. We enrolled 62 hemodialysis patients and followed them over a 12-month period. Patients were randomly assigned to receive ESA doses guided by the Smart Anemia Manager algorithm (treatment) or by a standard protocol (control). Dose recommendations, performed on a monthly basis, were validated by an expert physician anemia manager. The primary outcome was the percentage of hemoglobin concentrations between 10 and 12 g/dl over the follow-up period. A total of 258 of 356 (72.5%) hemoglobin concentrations were between 10 and 12 g/dl in the treatment group, compared with 208 of 336 (61.9%) in the control group; 42 (11.8%) hemoglobin concentrations were <10 g/dl in the treatment group compared with 88 (24.7%) in the control group; and 56 (15.7%) hemoglobin concentrations were >12 g/dl in the treatment group compared with 46 (13.4%) in the control group. The median ESA dosage per patient was 2000 IU/wk in both groups. Five participants received 6 transfusions (21 U) in the treatment group, compared with 8 participants and 13 transfusions (31 U) in the control group. These results suggest that individualized ESA dosing decreases total hemoglobin variability compared with a population protocol-based approach. As hemoglobin levels are declining in hemodialysis patients, decreasing hemoglobin variability may help reduce the risk of transfusions in this population.Anemia is a common complication of ESRD and is treated with erythropoiesis-stimulating agents (ESAs), iron, and/or blood transfusions. Effective anemia management with an ESA is challenging because of significant interindividual variability in erythropoietic response. A large ESA dose associated with an inability to achieve target hemoglobin (ESA resistance) may be a marker for increased risk of cardiovascular adverse events.^1–4 Until recently, the national guidelines for anemia management in ESRD patients recommended a hemoglobin target of 10–12 g/dl. The current ESA product label approved by the US Food and Drug Administration (FDA) stipulates treatment individualization to decrease the risk of transfusions. Furthermore, changes in reimbursement rules by Medicare, which provides coverage for a large majority of ESRD patients, have led to an evolution of ESA dosing patterns that results in lower average hemoglobin levels and more transfusions.⁵Ever since the introduction of ESAs, dialysis facilities have been providing standardized care using protocols derived from the national guidelines. The new FDA ruling emphasizes the need for individualized ESA dosing.^6,7 The goal of such individualization should be to maintain stable hemoglobin concentrations and prevent hemoglobin excursions below levels that typically trigger blood transfusions. However, as of now, no such level has been uniquely defined, and it is typically left to the clinician’s judgment to decide what hemoglobin level and/or presence of other symptoms should trigger transfusions.We and others have demonstrated the application of automatic control methods to ESA dosing.^8–10 We have shown that a population approach to ESA dosing, based on the principles of model predictive control (MPC), is comparable with a standard protocol.^8,9 We now present the results of a randomized clinical trial of an MPC-based individualized approach to ESA dosing. We tested the hypothesis that individualized ESA dosing improves the total hemoglobin variability defined as the proportion of hemoglobin measurements within a user-specified target (10–12 g/dl) compared with a standard protocol-based population approach. This study was registered at ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT00572533","term_id":"NCT00572533"}}NCT00572533).