Abstract

Abstract Background and Aims Anemia of CKD is common and managed with oral or intravenous iron, erythropoiesis-stimulating agents (ESAs) and, when necessary, red blood cell transfusions (RBCT). Reducing RBCT use is a goal in the management of anemia of CKD due to known short term (e.g., hyperkalaemia, heart failure) and longer term risks (e.g., allosensitization), but there is limited collated data on their use in Europe. A systematic literature review was conducted to evaluate the frequency of RBCT use among dialysis dependent (DD) and non-dialysis (ND) patients, and associated data reported for predictors of RBCT receipt, complications, healthcare resource use (HCRU), and costs. Method A comprehensive search strategy was used to retrieve real-world (RW) studies and randomized controlled trials (RCTs) conducted in DD and ND CKD patients with anemia using Embase and Medline (1980 to June 2022). Searches of conference abstracts, bibliographies and grey literature were also conducted. Studies which included European patients’ data are described here. Results Of the 3495 citations retrieved, 182 relevant studies were identified including 54 studies with European patients. Thirteen were RW studies including 12 quantifying the frequency of RBCT use (Table). In RW studies, the overall frequency of RBCT use ranged from 4.3–35.0% across studies and for key subgroups (n=10 studies: DD only studies, 8.4–33.9%; ND only studies, 4.3–35.0%). The number of RBCT units per patient-year (PY) ranged from 1.4–2.7 among DD patients (n=2 studies; no ND studies found). RBCT use appeared to vary by patient factors (iron/ESA use, CKD stage), by study design (e.g., length of follow-up) and across countries (but with no clear patterns in geographic variation). For the 41 RCTs including European patients (single country, n=3 studies, multi-country, n=38 studies), the overall frequency of RBCT use ranged from 0–21.6% (DD only studies, 0.4–21.6%; ND only studies, 0–14.8%), which was lower than those recorded in the RW studies. The rate of RBCT use in trials ranged from 3.5–66.0 events per 100 PY overall (DD only studies, 3.5–66.0; ND only study, 8.0); the number of RBCT units per PY ranged from 0.20–1.65 among DD patients (n=2 studies; no ND studies found). No studies used statistical modelling to quantify predictors of RBCT use while adjusting for potential differences between groups. One RW study from 1986 reported detection of human T-lymphotropic virus type III (HTLV-III; subsequently known as HIV) antibodies in 4 patients who had received RBCT (in a sample of 276 screened chronic HD patients). Of three RW studies reporting data on costs, two were >30 years old and one provided costs relating to receipt of inpatient RBCT in ND patients stratified by oral iron, low dose, or high dose intravenous iron use from 2013–2015 (n=111). Conclusion RBCT use forms part of the management of anemia of CKD in Europe and its use is variable but not infrequent. RBCT risk in RW studies appeared elevated compared to RCTs. There were no consistent patterns in geographic variation, but risk varied by patient factors and study design. There is currently limited European data reporting on frequency of associated complications, predictors of RBCT use, associated HCRU and costs. Funding: GSK (Study 218929).

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