Improvements in B lymphocyte function have been reported in hemodialysis patients receiving erythropoietin. The present investigation studied whether erythropoietin interferes with B cell function and the mechanisms of this effect. Antibody production by cultured peripheral blood mononuclear cells (PBMC) (7 days) from 15 dialysis patients before and during erythropoietin treatment and from 14 healthy controls was followed. IgG and IgA were formed less in the uremic group than in healthy subjects. After 8 weeks of erythropoietin (hematocrit rose from 19 to 31%) basal IgG formation by PBMC rose from 304 +/- 83 to 566 +/- 49 ng/ml (p less than 0.02), while IgA production rose from 380 +/- 121 to 563 +/- 362 ng/ml (p less than 0.01). IgM production, which appeared to be normal in uremia, remained unchanged during erythropoietin treatment. Production of IgG and IgA stimulated by pokeweed-mitogen was subnormal in uremia, but improved under erythropoietin therapy. To establish whether erythropoietin acted by itself or through correction of the renal anemia, healthy PBMC were directly incubated with 2 U/ml of erythropoietin. Under these conditions production of IgG (+19%), IgA (+28%), and IgM (+32%) was enhanced. Taken together these data indicate a direct stimulant effect of erythropoietin on B lymphocytes in end-stage renal failure.
Fifteen long-term hemodialysis patients suffering from stable anemia received recombinant human erythropoietin (r-huEPO). The hormone was given intravenously at the end of each dialysis session starting with a dose of 24 IU/kg. This dose was doubled when hemoglobin levels did not rise within 2 weeks. The number of reticulocytes started to increase after 14 days of treatment. The hematocrit rose from baseline values of 23.7 +/- 1.2% to 32.4 +/- 1.3% after 24 weeks of treatment. In parallel, hemoglobin values increased from 7.3 +/- 0.3 g/100 ml to 10.1 +/- 0.4 g/100 ml. As for side effects, 3 patients developed hypertension and 2 patients suffered from occlusions of their arterio-venous fistulas. There was no evidence of major organ dysfunctions, toxic effects, allergic reactions, or antibody formation. These data show that r-HuEPO is able to correct the anemia of patients undergoing hemodialysis treatment.
The majority of patients with renal insufficiency suffer from a normochromic, normocytic anaemia. This renal anaemia affects the quality of life of these patients and reduces their chance of survival. Despite the availability of recombinant human erythropoetin for the treatment of renal anaemia, many patients do not achieve the target haemoglobin concentration of more than 11 g/dl. A major factor contributing to suboptimal correction of renal anaemia and reduced responsiveness to epoetin is a lack of iron availability to the stimulated erythropoesis.Thus, forthe majority of patients with renal insufficiency intravenous iron therapy will be the treatment of choice to replete and maintain adequate iron stores.
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