Reconsideration of the anemia management strategy for chronic kidney disease and dialysis patients

Anemia is common in patients with nondialysis-dependent (NDD) and dialysis-dependent (DD) chronic kidney disease (CKD). Although the capacity to produce substantial erythropoietin (EPO) remains high in these patients, insufficient EPO production is regarded as the main cause of renal anemia. Although erythropoietin-stimulating agent (ESA) administration has become the mainstay of renal anemia treatment, this treatment results in an unfavorable prognosis when the hemoglobin level becomes > 13 g/dL with the administration of these agents, and evidence for the optimal lower limit of hemoglobin level is scarce. Anemia is also common in patients with heart failure. Structural renal disease, which can reduce EPO production, is infrequent but is characterized by a low serum EPO level. ESA use for anemia treatment in heart failure patients is associated with more thromboembolic adverse events and is therefore not recommended. Given that milder forms of heart failure or cardiac stress caused by volume overload are common in oliguric or anuric patients with NDD- and DD-CKD, cardiac stress caused by volume overload can also be an important cause of anemia in these patients. The dynamics of serum endogenous EPO and reticulocyte levels differ according to the cause of anemia. During gradual anemia exacerbation due to renal dysfunction in patients with NDD-CKD, the serum endogenous EPO and reticulocyte levels do not decrease but rather increase. These levels increase after massive hemorrhage in patients on hemodialysis. In contrast, the serum EPO and reticulocyte levels decrease during anemia exacerbation due to mild cardiac stress caused by volume overload in patients on hemodialysis. After water removal, anemia is ameliorated without ESA administration, which is not due to hemoconcentration. In patients with NDD- and DD-CKD, in addition to decreased EPO production capacity, there are other causes of anemia. Thus, the strategy for anemia management should not be uniform. To improve the outcomes of these patients, in addition to the current strategy for anemia management in which target hemoglobin levels are achieved by adjusting the ESA dose, other approaches for anemia management based on the cause of anemia are needed. Possible problems and future improvements in the current strategy for anemia management in patients with NDD- and DD-CKD are discussed.