Subcutaneous recombinant human erythropoietin in chronic renal allograft dysfunction
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Transplantation Original article
Subcutaneous recombinant human erythropoietin in chronic renal allograft dysfunction Christoph Aufricht1, Jennifer L. Marik2, and Robert B. Ettenger2 1 2
Kinderdialyse der UniversitaÈts-Kinderklinik, University of Vienna, Vienna, Austria Department of Pediatric Nephrology, University of California, Los Angeles School of Medicine, Los Angeles, California, USA
Received February 13, 1997; received in revised form and accepted June 26, 1997
Abstract. We investigated the efficacy and safety of subcutaneous recombinant human erythropoietin (rHuEpo) in 25 children with chronic renal allograft dysfunction (13 girls, 12 boys, mean age 15.8+4.2 years) for a treatment period of 9 ± 162 (median 43) weeks. rHuEpo was started once weekly at a dose of 105+25 U/kg per week in 16 children, twice weekly at a dose of 175+70 U/kg per week in 6 children, and three times weekly at a dose of 270+28 U/kg per week in 3 children. The hematocrit increased in 21 children from 23.2%+3.1% to 33%+3.1% within 7.2+4.9 weeks at a mean rate of 1.98%/week. The hematocrit increase and rHuEpo starting dose were linearly related (delta hematocrit/week = 0.8+0.08 U/kg per week, r = 0.44, P 50.05). The maintenance dose was 74+23 (43 ± 114) U/kg per week. Four children failed to reach the target hematocrit, most likely due to noncompliance. Seventeen recurrences of anemia (ªanemic episodesº) during rHuEpo therapy were identified in 12 children, mostly associated with acute or insidious deteriorations in graft function. There was no acceleration of progression of graft dysfunction with rHuEpo treatment. We conclude that subcutaneous rHuEpo at a single weekly dose of 100 IU/kg per week is highly effective in children with chronic graft dysfunction. Children who appear to be rHuEpo resistant or experience rHuEpo-resistant episodes should be assessed for noncompliance, changes in graft function since the last dosage adjustment, and blood loss, such as seen in dysfunctional uterine bleeding in adolescent girls. Key words: Anemia ± Renal transplantation ± Chronic rejection ± Chronic graft dysfunction ± Non-compliance
Introduction Renal anemia significantly impairs the quality of life of children with chronic renal failure. Following successful renal transplantation, erythropoietin produced by the transplanted kidney stimulates red cell production, thus normalizing red blood cell count [1]. Chronic decline in graft function is frequently accompanied by gradual redevelopment of renal anemia. However, the pathophysiology of anemia after renal transplantation is more complex than in primary renal failure [2]. Red blood stem cell proliferation may be depressed by immunosuppressive treatment, such as azathioprine [3]. Chronic rejection may represent a state of chronic inflammation [4]. Inflammation causes an increased clearance of iron from plasma, an increased uptake of iron by the reticuloendothelial system, and therefore a decreased iron supply for the marrow, hampering erythropoiesis [5]. Steroid therapy may impair gastrointesti
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