Clinical Practice Guidelines for evidence-based use of erythropoietic-stimulating agents

Abstract

BACKGROUND In patients with chronic kidney disease (CKD), anemia is associated with left ventricular hypertrophy and adverse cardiovascular and clinical outcomes. Moreover, anemia is associated with a reduction in quality of life, particularly when the hemoglobin level drops below 100 g/l. 1 Thus, the goal of treating anemia in iron-replete patients with erythropoietic-stimulating agents (ESAs) is to reduce the likelihood of cardiovascular events, improve patients’ survival, and improve patients’ quality of life while minimizing any deleterious effects of the drug. Given that ESAs increase blood pressure and have other potential side effects, it is also important to assess whether the quantity of the ESA used might contribute to adverse events such as more rapid deterioration of kidney function, earlier requirement for dialysis, and vascular access failure. It is acknowledged that, if left untreated, patients with severe anemia may require blood transfusions, which have associated risks and costs, and possible implications for patients awaiting a kidney transplant. In light of this, in most developed countries, the question for CKD patients with significant anemia has often not been whether to use ESAs, but when to use them and what target hemoglobin level to aim for. 2 The earliest anemia correction studies in nondialysischronic kidney disease (ND-CKD) and hemodialysis-chronic kidney disease (HD-CKD) patients compared the use of erythropoietin a with placebo. 3–5 Most early studies were not designed and powered to examine clinical outcomes other than quality of life, and no differences were apparent in such other outcomes. Several of the studies showed improvements in quality of life compared with placebo. 3–5 Subsequent randomized control trials (RCTs) have tended to examine the impact of using ESAs to achieve different target hemoglobin level ranges on surrogate endpoints, such as left ventricular (LV) mass, where patients with the lower hemoglobin target would be less likely to require the use of an ESA or would require lower doses to maintain the prespecified lower target hemoglobin. Two RCTs 6,7 in HDCKD patients compared with the use of ESAs to achieve intermediate hemoglobin and high hemoglobin targets. Although both studies showed no difference in progression of LV mass, the higher target hemoglobin led to improved quality of life in some of the domains, but the size of this