Anemia in conventional hemodialysis: Finding the optimal treatment balance

Renal anemia is a serious and common complication in hemodialysis ( HD ) patients. The introduction of erythropoiesis‐stimulating agents ( ESA s) has dramatically improved hemoglobin levels and outcomes. Several interventional studies reported that excessive correction of anemia and the massive use of ESA can trigger cardiovascular disease ( CVD ), and consequently may worsen the prognosis of patients undergoing HD . Therefore, it has been widely recognized that large doses of ESA should be used with caution. An effective use of iron preparations is required to yield the optimal effect of ESA . It is well‐known that iron utilization is inhibited under pathological conditions, such as chronic inflammation, resulting in ESA resistance. It is postulated that a new class of therapeutic agents for renal anemia, hypoxia inducible factor prolyl hydroxylase ( HIF ‐ PH ) inhibitors, will have beneficial treatment effects in patients on HD . HIF is induced by hypoxia and promotes erythropoietin production. In the absence of a hypoxic state, HIF is decomposed by the HIF catabolic enzyme. HIF ‐ PH inhibitors inhibit this degrading enzyme and stimulate endogenous erythropoietin production via HIF induction. Additionally, HIF ‐ PH inhibitors promote effective utilization of iron and raise erythropoietin to physiological concentrations. Accordingly, HIF ‐ PH inhibitors improve anemia and iron metabolism. It appears that this effect persists irrespective of chronic inflammatory conditions. HIF ‐ PH inhibitors do not overshoot erythropoietin above physiological concentrations like ESA s. Therefore, it is hypothesized that HIF ‐ PH inhibitors would not increase the risk of CVD in patients undergoing HD .