[Erythropoietin-beta in the treatment of anemia in patients with chronic renal insufficiency].

INTRODUCTION: Anemia is an early sign of chronic renal failure (CRF). Although multifactorial in origin, insufficient erythropoietin (EPO) synthesis is one of the most important factors. Other causes are: decreased erythrocyte survival (from 120 days to 70-80 days), chronic blood loss (mainly gastrointestinal and gynecological), inhibitors of erythropoiesis, inflammatory cytokines (IL-1, TNF-alpha, IFN-gamma) and malnutrition (folic acid, L-carnitine and vitamin B12 deficiency). Chronic blood loss may cause iron deficiency in about 25% of patients. Correlation between EPO level and glomerular filtration rate (GFR) is well preserved, but negative feed-back loop between hemoglobin and EPO is disturbed in patients with CRF.

CONSEQUENCES OF GRF: The consequences of renal anemia are mainly cardiovascular; left ventricular hypertrophy (LVH) is often found at the start of dialytic therapy. Cardiovascular morbidity [especially LVH and congestive heart failure (CHF)] and mortality highly correlate with the degree of anemia. In addition, anemia affects patient rehabilitation and quality of life. It positively correlates with the degree of physical activity, sleep and general well-being.

ERYTHROPOIETIN THERAPY: Optimization of erythropoietin therapy includes awareness of target hematocrit and hemoglobin, defining the renal anemia management period (RAMP), drug dosage and mode of application and significance of adjuvant therapy. Anemia should be treated early during the course of renal failure, even when GFR falls below 50 ml/min. According to dialysis outcomes quality initiative (DOQI) guidelines, target values are 0.33-0.36 L/L for hematocrit and 110-130 g/l for hemoglobin. Early administration is recommended especially in high-risk patients: the elderly, diabetics and those with coronary artery and peripheral artery diseases.

EFFECTS OF EPO THERAPY: Individualization and close monitoring of therapy are very important and weekly rise in hematocrit (Ht) should not exceed 1%. More recent studies justify the normalization of Hb/Ht values--patients with normal Hb/Ht values have had the lowest mortality. In addition, normalization of Hb/Ht prevented LVH. Subcutaneous administration has priority compared to intravenous. Adjuvant therapy includes: iron, vitamin C and D, L-carnitine, folic acid, cytokines and growth factors. Intravenous iron administration has priority upon oral; target levels are 400-800 for ferritin um/ml and > 20 for transferrin saturation. Vitamin C (500 mg, after every hemodialysis) is very helpful in cases of functional iron deficiency. L-carnitine stabilizes the membrane of erythrocytes and prolongs their lives. Folic acid (10 mg/day) enhances response to EPO. Apart from correction of hematological parameters, erythropoietin therapy significantly improves left ventricular hypertrophy, quality of life, nutrition, sexual activity, carbohydrate and lipid metabolism, cognitive function and sleeping function. Given in predialysis period, it may slow progression of renal failure, prevents cardiovascular and overall morbidity and improves survival in dialysis population.

CONCLUSION: The reasons for inadequate erythropoietin response are unrecognized bleeding, iron deficiency and infection/inflammation. Adverse events are very rare and predictable; they can be avoided with careful dosage and follow-up of patients. In conclusion, EPO-therapy is well established and efficient for renal anemia in dialysis and pre-dialysis patients.