Isolated serum-free perfused rat kidneys release immunoreactive erythropoietin in response to hypoxia

The renal glycoprotein hormone erythropoietin (Epo) interacts with erythrocytic progenitors to stimulate their proliferation and differentiation in the bone marrow. The renal 02-sensing mechanism in the control of the synthesis of Epo is still poorly understood. Therefore, the capacity of isolated rat kidneys to produce Epo during hypoxic and anemic perfusion was studied. The kidneys were perfused at a constant perfusion pressure of 100 mm Hg with a substrate-enriched Krebs-Hen-seleit solution containing 60 g/liter BSA and freshly drawn human erythrocytes. Epo was measured by RIA. When the kidneys were perfused at an arterial pO₂of 720 or 150 mm Hg (hematocrit, 5%), Epo production was very low (0.1-0.2 U/g kidney within 3 h of perfusion). When the arterial pO₂was lowered to 35 or 20 mm Hg, Epo production increased to 0.4 and 0. 9 U/g kidney, respectively. The release of Epo during hypoxic perfusion (pO₂35 and 20 mm Hg) was little affected by changes in the hematocrit, i.e. the O₂-carrying capacity of the perfusion medium over a wide range (0-40%). These results indicate that the production of Epo in the isolated perfused kidney depends on the availability of O₂and can be modulated by changes in the arterial pO₂.