**10. Epoetin-resistant anemia**

Anemia in CKD patients induces eccentric LVH and exacerbates myocardial ischemia, increasing cardiovascular mortality in dialysis CRS [110, 111]. Erythropoietin drugs improve the quality of life of dialysis patients. However, the mortality-reducing effect of erythropoietin in dialysis CRS has not been proven, and the most effective and safe target Hb level is not established. The currently recommended target Hb level of 10–12 g/dL does not stimulate sufficiently neoangiogenesis and endothelial stem cells activity.

Resistant anemia often develops within MIA syndrome (under the influence of chronic inflammation, acidosis, iron malabsorption, vit. B12 and folic acid deficiency), as well as because of ineffective HD syndrome and hyperparathyroidism, requiring the unusually high doses of erythropoietin. Since this therapy is often complicated by poorly controlled hypertension and thrombosis, combined antihypertensive therapy, complete correction of iron deficiency, vit. B12 and metabolic acidosis, and control of the coagulation system are indicated [112]. Intensification of HD regimen, correction of hyperparathyroidism, influence on chronic inflammation syndrome (anti-cytokine drugs, etc.) are of great importance for overcoming resistance to epoetin. At critically low hemoglobin, blood transfusions can be used.

Recently, a new group of drugs has been proposed to treat anemia, the so called hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs). HIF-PHIs promote erythropoiesis primarily through increased endogenous EPO production and modulation of iron metabolism. The results of phase 2 and 3 clinical trials have shown their advantages, such as decreased hepcidin levels, better iron utilization and thus less need for iron, the ability to influence the background of inflammation without increasing the dose [113]. These drugs will probably find their use in patients with epoetin-resistant anemia associated with both inflammation and iron metabolism disorders.
