Erythropoietin activity in acutely uremic mice

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.