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Use of Recombinant Human Erythropoietin in Children Undergoing Dialysis

Chronic renal failure (CRF) in childhood is inevitably associated with the development of a normochromic, normocytic, hypoproliferative anemia (50). This so-called renal anemia (RA) usually starts in children when their glomerular filtration rate has declined to 35 mVmid1.73 m2 (76) and is more pronounced than in adults (55). Its etiology is multifactonal and due to the combination of extracorpuscular hemolysis, increased occult intestinal blood loss and reduced erythropoiesis (48, 76). The latter is mainly the consequence of an inadequate renal erythropoietin (EPO) secretion (46, 51) related to the degree of anemia. This relative EPO deficiency becomes an absolute one when the stage of terminal renal failure has been reached, where hypoxiainduced EPO secretion has been lost. Accordingly, EPO concentrations are extremely low in children on hemodialysis (HD), and are comparable to values obtained in bilaterally nephrectomized adults, whereas with CAPD, higher levels are detected (8, 22). Since gastrointestinal blood loss is increased during HD, it is not surprising that the degree of RA is more pronounced in children on HD than on CAPD (53). To what extend the EPO secretion of peritoneal macrophages contributes to the serum EPO concentration remains unknown (2 1). With progression from preterminal to terminal renal failure (TRF), RA is usually associated with the development of transfusion dependency. In children, about 100 ml packed red blood cellslm2 BSMmonth were required following initiation of CAPD; three fold that amount was required after beginning HD (53). Treatment modalities such as subtotal parathyroidectomy and oxandrolone were unable to obviate the need for blood transfusions, so, in the past, children with TRF progressively suffered from hemosiderosis unless an early kidney graft (i.e., within one year after starting dialysis) was performed (77). Moreover, the use of blood transfusions predisposes to additional long-term complications such as transmission of hepatitis C, development of cytotoxic HLA antibodies, and suppression of erythropoiesis (55). Consequently, transfusion policy was rather restrictive in the past and transfusions with a hemoglobin (Hb) concentration >5-6 g/dl were avoided. Therefore, uremia was usually