The response of erythropoietin to dietary protein in human renal disease

The response of erythropoietin to dietary protein was examined in nine subjects with a variety of glomerular diseases. They were randomly assigned by using a crossover design to two 11-day periods, one on a high-protein diet (2 gm/kg/day) and the other on a low-protein diet (0.55 gm/kg/day). The high-protein diet was associated with increased urinary erythropoietin excretion (4.28 ± 0.84 U/24 hr vs 1.28 ± 0.16 U/24/hr; p < 0.05), increased serum erythropoietin concentration (22 ± 2 mU/ml vs 10 ± 2 mU/ml; p < 0.05), and increased reticulocyte count (3.0 ± 0.8 vs 1.6 ± 0.4; p < 0.05), demonstrating that erythropoietin production by the diseased kidney was still responsive to dietary protein manipulation. To examine whether changes in erythrocyte survival could be responsible for the differences in erythropoietin production, red cell survival was measured in two groups of subtotally nephrectomized rats, one group ingesting a high-protein diet (30%) and the other a low-protein diet (6%). No difference in erythrocyte survival rate was found. Reticulocyte counts were, however, elevated on the high-protein diet. We conclude that in the diseased kidney, a high-protein diet, perphaps by increasing renal O₂ consumption, directly stimulates erythropoietin production.