Abstract

Abstract Background and Aims In clinical practice, the treatment of renal anemia is challenging. The attainment of target levels for hemoglobin is often low, due to the high incidence of infections, hyporesponsiveness to erythropoietin stimulating agents (ESA), and suboptimal prescribing of ESA and iron. Several interventions to improve the treatment of renal anemia have been developed, two of them being algorithm-managed dosing and pharmacist-managed dosing of ESA. We performed a systematic review to identify and summarize these two types of interventions and to determine their effectiveness in improving the treatment of renal anemia. Method We followed the PRISMA guidelines for systematic reviews. Studies that explored the effect of algorithm-managed and pharmacist-managed dosing of ESA in adult patients with renal anemia were evaluated for inclusion. No restrictions were set on outcome parameters. All observational and interventional studies that included a control group and had a follow-up of at least six months, were eligible for inclusion. Only full-length articles were considered for inclusion. PubMed, Embase, Web of Science, and the Cochrane Library were searched from their inception through July 2022. All included studies were evaluated by two independent reviewers. The quality of studies was assessed by the Newcastle Ottawa Scale and the risk of bias was assessed by the ROBINS-I and RoB1 tools. Data were summarized and tabulated. Studies were grouped according to intervention type, study design, and risk of bias. The protocol of this study was registered in PROSPERO (International Prospective Register of Systematic Reviews) with ID CRD42021243678. This study was funded by the Franciscus Gasthuis and Vlietland hospital. Results A total of 120 articles were assessed for inclusion, and after screening, 16 articles were included with a total number of 3777 patients. Available evidence was scarce and generally of low to moderate quality; only two RCTs could be identified. All but one of the other studies were observational in nature. The risk of bias was serious in all but one study. Study follow-up was relatively short, varying between six and thirteen months. In six studies, ESA dosing was pharmacist-managed and in one study ESA dosing was algorithm-managed, in nine studies a combination was used. The quality of the intervention description was low to moderate and interventions generally were not reproducible. Although heterogeneity was substantial for outcome parameters, four types of outcome parameters could be determined: hemoglobin/hematocrit, ESA dose and expenditure, iron status, and iron dose. Quantitative synthesis of data was not possible due to the substantial heterogeneity in outcome parameters and the high risk of bias. Therefore, the effectiveness of algorithm-managed and pharmacist-managed dosing of ESA in renal anemia could only be qualitatively assessed for the four types of outcome parameters. In six of the fifteen studies that reported on hemoglobin or hematocrit, the percentage of patients within target levels was significantly higher for the intervention group, whereas in four studies no significant difference was found. Six of the ten studies that reported on ESA dose or ESA expenditure found a significant decrease in ESA dose or expenditure in the intervention group, whereas two studies reported no significant difference. In five of the seven studies that reported on iron status, a significantly higher iron status was found in the intervention group, whereas one non-inferiority study reported no significant difference. In three of the four studies that reported on the iron dose, no significant difference was found between the intervention and the control group, whereas in one study the iron dose was significantly higher in the intervention group. Conclusion Available evidence was scarce with a high risk of bias, and quantitative data synthesis was not possible. Therefore, no definite conclusions could be drawn on the effectiveness of algorithm-managed and pharmacist-managed dosing of ESA in renal anemia. Consequently, no recommendations on the implementation of either of the two interventions could be made.

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