Model predictive control of erythropoietin administration in the anemia of ESRD.
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.


METHODS
(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.


METHODS
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.


METHODS
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).


CONCLUSIONS
MPC of ESAs may result in improved anemia management.
D000368:Aged; D000465:Algorithms; D000740:Anemia / Q000188:drug therapy* / Q000453:epidemiology / Q000209:etiology*; D003198:Computer Simulation; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016571:Neural Networks, Computer; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D016896:Treatment Outcome
D011994:Recombinant Proteins; D004921:Erythropoietin