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

Background: Correction of anaemia in moderate toadvanced renal failure is still a matter of debate because of postulateddetrimental effects of erythropoietin on the progression of renal damage.Methods: The renal effects of early normalization ofhaematocrit (Htc) by erythropoietin (rHuEpo) were investigated from thetime of 5/6 nephrectomy up to 8 weeks post-intervention in three groups ofremnant kidney model rats: untreated controls (CON), rats receiving 100UI/kg body-wt of rHuEpo i.p. twice a week (EPO), and rats receiving rHuEpoin which periodic phlebotomies maintained Htc similar to the value of thecontrol group (PHL). The latter group was included to evaluate the directeffects of rHuEpo on renal damage, i.e. independent from Htc correction.Results: Two weeks after renal ablation (basal), Htcdecreased in CON and PHL (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 EPOrats (78.9±1.2% to 48.8±1.5%, P<0.05vs other groups). Thereafter Htc did not changethroughout the remaining period in all groups. At the end of the study,with respect to basal, resting blood pressure increased significantly bythe 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 alterationsand glomerular hypertrophy/sclerosis was similar in CON and EPO rats, andwas significantly more severe than in the phlebotomized group. The onlydifference detected between CON and EPO group was the greater mesangialhypercellularity in rHuEpo-treated rats. Conclusion:In uraemic rats, chronic treatment with rHuEpo aimed at normalization ofHtc beginning the early stage of renal failure does not inevitably accountfor a rise in systemic blood pressure. In addition, neither erythropoietinper se nor the correction of haematocrit acceleratesthe progression of renal damage when blood pressure remains constant.