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Erythropoietic activity produced by exogenous erythropoietin (Ep) is markedly reduced in Swiss mice rendered uremic by bilateral nephrectomy or bilateral ureteral ligation. Exogenous Ep causes a greater increase in erythropoiesis in germfree Swiss mice as compared with non-germfree mice, but the germfree mice show a more drastic reduction of erythropoiesis in uremia. Heme production in blood, spleen, and femoral marrow retains its typical pattern in uremia; there is no shift of erythropoiesis among the three sites. Production of endogenous Ep in uremic mice is less by a factor of 2-3 than that in intact mice whereas the reduction is by a factor of almost 100 in anephric mice. The data suggest that the anemia associated with uremia is the result of two phenomena: (1) a decreased production of Ep and (2) a diminished erythropoietic response to Ep.
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