A model for erythropoiesis in experimental chronic renal failure

Chronic renal failure (CRF) in rats was induced by various subtotal nephrectomy procedures. Plasma creatinine concentrations ([Creat]p) were consistently elevated in partially nephrectomized (PNX) rats (P less than 0.001) and renal function ([Creat]p-1) was correlated with the amount of intact renal tissue (r = 0.624, P less than 0.001). Red blood cell (RBC) production in uraemic and non-uraemic rats was assessed using the recovery of packed cell volume (PCV) and the production of reticulocytes in response to acute blood loss (5, 10, 15 and 20 ml kg-1 body wt). PCV recovery was significantly delayed and failed to reach pre-bleed values for up to 28 d in PNX rats compared with full recovery within 8 d in controls. Linear relationships between the index of reticulocyte production (RP1) and blood loss induced falls in PCV were found in PNX (r = -0.679, P less than 0.001) and control rats (r = -0.696, P less than 0.001). The index of RBC production was lower in PNX rats compared with controls. This was attributed to a reduced erythropoietin (Ep) mediated reticulocyte response to acute blood loss in PNX rats. PNX rats developed a normocytic, normochromic form of anaemia in which the red blood cell volume (RBCV) and plasma volume (PV) were both appropriate for measured PCVs. The reduced RBC production response in experimental CRF may explain the development of anaemia in PNX rats, even though steady state erythropoiesis may eventually be established at a reduced level of PCV. Furthermore, the quantitative evaluation of RBC production in response to acute blood loss provides a further model for the assessment of agents which may stimulate erythropoiesis in CRF.