The impact of early normalization of haematocrit by erythropoietin on renal damage in the remnant kidney model

Background. Correction of anaemia in moderate to advanced renal failure is still a matter of debate because of postulated detrimental effects of erythrupoietin on the progression of renal damage. Methods, The renal effects of early normalization of haematocrit (Htc) by erythropoietin (rHuEpo) were investigated from the time of 5/6 nephrectomy up to 8 weeks post-intervention in three groups of remnant kidney model rats: untreated controls (CON), rats receiving 100 UI/kg body-wt of rHuEpo i.p, twice a week (EPO), and rats receiving rHuEpo in which periodic phlebotomies maintained I-Etc similar to the value of the control group (PHL). The latter group was included to evaluate the direct effects of rHuEpo on renal damage, i.e. independent from Htc correction. Results. Two weeks after renal ablation (basal), I-Etc decreased in CON and PHL rats (from 49.3 +/- 1.4% to 43.2 +/- 1.1, P < 0.05 and from 49.6 +/- 1.1 to 43.3 +/- 1.5%, P < 0.05 respectively), while it remained consistently normal in EPO rats (48.9 +/- 1.2% to 48.9 +/- 1.5%, P < 0.05 vs other groups). Thereafter Htc did not change throughout the remaining period in all groups. At the end of the study, with respect to basal, resting blood pressure increased significantly by the same extent in CON (+13 +/- 2%) and EPO rats (+15 +/- 5%), while it remained constant in PHL rats. Notably, creatinine clearance significantly decreased in CON (-53 +/- 8% vs basal) and EPO (-38 +/- 8% vs basal), while it did not change in PHL rats. Likewise the degree of proteinuria as well as renal morphologic alterations and glomerular hypertrophy/sclerosis was similar in CON and EPO rats, and was significantly more severe than in the phlebotomized group. The only difference detected between CON and EPO group was the greater mesangial hypercellularity in rHuEpo-treated rats. Conclusion. In uraemic rats, chronic treatment with rHuEpo aimed at normalization of Htc beginning the early stage of renal failure does not inevitably account for a rise in systemic blood pressure. In addition, neither erythropoietin per se nor the correction of haematocrit accelerates the progression of renal damage when blood pressure remains constant.