Abstract
BackgroundAnaemia of chronic kidney disease increases the risk of death and adverse events, but can be managed using erythropoiesis stimulating agents (ESAs). However, recent evidence suggests that targeting a higher haemoglobin concentration ([Hb]) increases mortality risk, and both higher [Hb] targets and ESA doses have been implicated. Nonetheless, a causative role has not been demonstrated, and this potential relationship requires further appraisal in such a complex patient group.MethodsThe relationship between the haematopoietic response to ESAs and patient survival in 302 stable, prevalent dialysis patients was explored in a prospective, single-centre study. Clinical and laboratory parameters influencing mortality and ESA resistance were analysed. Patients were stratified into 5 groups, according to their [Hb] and ESA dosage, and were followed for 2 years.ResultsLittle difference in co-morbidities between groups was identified. 73 patients died and 36 were transplanted. Initial analysis suggested a direct relationship between mortality and ESA dosage. However, Cox proportional hazards multivariate analysis demonstrated mortality risk was associated only with age (adjusted HR per year: 1.061, 95% CI 1.031-1.092), dialysis duration (adjusted HR: 1.010, 95% CI 1.004-1.016), peripheral vascular disease (adjusted HR: 1.967, 95% CI 1.083-3.576) and CRP (adjusted HR: 1.024, 95% CI 1.011-1.039). Mortality was increased in patients poorly responsive to ESAs (55.5%).ConclusionESA dose does not appear to contribute substantially to mortality risk in dialysis patients. Instead, age and co-morbidities appear to be the critical determinants. A poor response to ESAs is a marker of overall poor health status.
Highlights
Anaemia of chronic kidney disease increases the risk of death and adverse events, but can be managed using erythropoiesis stimulating agents (ESAs)
ESA dose was expressed as IU/kg/week
Demographic and laboratory assessments Data collected at baseline included age, sex, aetiology of chronic kidney disease (CKD), blood pressure, co-morbidities, body mass index (BMI), dialysis mode, and duration of end stage kidney disease (ESKD), including duration of dialysis and/or past renal transplantation
Summary
Anaemia of chronic kidney disease increases the risk of death and adverse events, but can be managed using erythropoiesis stimulating agents (ESAs). Erythropoiesis stimulating agents (ESAs) have been used to raise and maintain haemoglobin concentrations ([Hb]) since a link between anaemia, impaired quality of life, and adverse outcomes in patients with chronic kidney disease (CKD) was first suggested [1,2,3]. In one recent randomised controlled trial in The mechanism for such an increase in the adverse event rate remains unclear, with suspicion falling on both the targeted [Hb] and ESAs themselves as causative agents [8]. It is important to recognise that the capacity of each of these trials to determine the true relationship has been limited by inherent trial design [12] This fact was highlighted by an additional recent study, which found that after adjusting for multiple factors (including ESA dose), mortality reduced with increasing [Hb] in a prospectively followed incident cohort of Spanish haemodialysis patients [13]
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