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Due to insufficient endogenous production of erythropoietin, chronic kidney disease patients with anemia are often treated by the administration of recombinant human erythropoietin (EPO). The target of the treatment is to keep the patient's hemoglobin level within a normal range. While conventional methods for guiding EPO dosing used by clinicians normally rely on a set of rules based on past experiences or retrospective studies, model predictive control (MPC) based dosage optimization is receiving attention recently. The objective of this paper is to incorporate the hemoglobin response model uncertainty into the dosage optimization decision making. Two methods utilizing Conditional Value at Risk (CVaR) are proposed for hemoglobin control in chronic kidney disease under model uncertainty. The first method includes a set-point tracking controller with the addition of CVaR constraints. The second method involves the use of CVaR directly in the cost function of the optimal control problem. The methods are compared to set-point tracking MPC and Zone-tracking MPC through computer simulations. Simulation results demonstrate the benefits of utilizing CVaR in stochastic predictive control for EPO dosage optimization.

BackgroundOngoing discussion on anaemia management and target haemoglobin (Hb) levels in patients on haemodialysis with erythropoietin treatment require a systematic approach in evaluating current practice. Aim of the present study was to develop a new classification system to easily monitor Hb trajectories and categorise patients on haemodialysis.MethodsRoutine data from five dialysis centres in the USA collected between 2010 and 2016. Data were anonymised and only those from patients with fortnightly Hb values were included in the analysis. Entries on blood parameters and medication were standardised to achieve overall comparability. Data from each patient was grouped in periods of 120 days. Hb values above or below the target level of 10–12 g/dL were counted for each period. Periods were then assigned to Hb-classes according to the number of Hb values out of range per period: Hb-class I with 0–2, Hb-class II for 3–5 and Hb-class III for ≥6 values out of range.ResultsRecords from 3349 patients with fortnightly Hb values, information on haemodialysis data, laboratory parameters correlated to red blood cells and data on medication with erythropoiesis-stimulating agents (ESAs) were available. Patients were 64.4±15.9 years old; 55.0% were men. Statistical analysis revealed significant differences between Hb-classes in all of the examined parameters, except erythrocytes mean corpuscular volume and C reactive protein above the threshold, with more critical values in higher Hb-classes. The usage of ESAs showed a mean difference between Hb-class III and Hb-class I of 6.4 units/day and kilogram body weight in a 120-day period.ConclusionOur classification system allows an easily achievable overview of the patients’ responsiveness and performance of Hb management. Integrated into a disease management programme or continuous quality improvement, the classification delivers an instant appraisal without complex statistical or mathematical processing.

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