Background: Variable hemoglobin (Hb) response to erythropoiesis-stimulating agents (ESAs) may result in adverse outcomes. New methods are needed to determine the appropriate dose of ESA to maintain the target Hb level.
Design: (1) Observational study to develop an algorithm for model predictive control (MPC) by using an artificial neural network model of Hb response to ESA. (2) Computer simulation to test MPC versus a conventional anemia management protocol (AMP). (3) Clinical trial to test MPC.
Setting & participants: The MPC was developed from historic data from 186 long-term hemodialysis patients at the University of Louisville, KY. Testing by simulation occurred in 60 hypothetical patients generated from random sampling of the 186 patients. The trial included 9 hemodialysis patients who received ESA doses based on MPC recommendations over 6 months.
Predictor: Management by means of MPC or AMP. OUTCOME OF INTEREST: Achieved Hb level and variability measured by means of the difference between achieved Hb level and target Hb level of 11.5 g/dL and erythropoietin dose. In the trial, Hb level deviation from target was compared in the same subjects between the study (last 4 of 6 months on MPC) and control (4 months on AMP immediately proceeding the study period) periods.
Results: In simulation, achieved Hb levels were 12.3 +/- 0.6 g/dL for AMP and 11.6 +/- 0.4 g/dL for MPC (P < 0.001), mean SDs were 0.75 +/- 0.30 g/dL for AMP and 0.60 +/- 0.21 g/dL for MPC (P < 0.01), and mean absolute differences from target were 0.8 +/- 0.6 g/dL for AMP and 0.3 +/- 0.3 g/dL for MPC (P < 0.001). In the trial, achieved Hb levels were 11.9 +/- 1.1 g/dL for AMP and 11.8 +/- 0.6 g/dL for MPC (P = 0.8), mean SDs were 0.86 +/- 0.60 g/dL for AMP and 0.64 +/- 0.33 g/dL for MPC (P = 0.4), and mean absolute differences from target were 1.19 +/- 0.79 g/dL for AMP and 0.79 +/- 0.50 g/dL for MPC (P = 0.02).
Conclusion: MPC of ESAs may result in improved anemia management.