Anemia is common in patients with chronic kidney disease (CDK), contributes to reduced Quality of Life (QoL) and is associated with cardiovascular disease, morbidity and mortality. Epoetin raises hemoglobin (Hb) and increases QoL and physical exercise capacity. Because of concerns about safety and economics, current anemia treatment with epoetin aims to achieve subnormal Hb (110-120 g/l). Normalization of Hb may be of additional benefit regarding QoL and cardiovascular effects. The present study examines the effects of Hb normalization with epoetin on safety variables, QoL, graft function after kidney transplantation, dialysis adequacy, hemorheology, hemodynamics and cardiac autonomic function in CKD patients. In a randomized, multicenter study comprising 416 pre-dialysis and dialysis patients no difference was observed between patients treated to a normal or a subnormal Hb level on mortality, thrombovascular events, serious adverse events, vascular access thrombosis and residual renal function. QoL was enhanced in a subgroup of hemodialysis patients. Pretransplant epoetin treatment directed toward normal Hb levels did not result in worse graft function during 6 postoperative months. Dialysis adequacy was reduced in a subgroup of hemodialysis patients after normalization of Hb. The blood flow properties of pre-dialysis patients were altered. The hemorheological investigation demonstrated that Hb normalization caused a parallel increase in hematocrit and blood viscosity without other hemorheological changes. While the total peripheral resistance index increased, the cardiac index (CI) decreased. In a separate study cardiac autonomic function, measured by heart rate variability, was decreased in pre-dialysis patients. It was improved, but not fully normalized, by Hb normalization. On the basis of this study, Hb normalization with epoetin appears to be safe and increases QoL in hemodialysis patients though may result in lower dialysis adequacy and increased blood pressure. A reduction in CI and improved cardiac autonomic function indicate a positive effect on cardiovascular function.

Dans le but de vérifier l’impact d’un changement soudain dans l’agrégation érythrocytaire sur certains paramètres cardiovasculaires, une transfusion par échange sanguin du tiers du volume a été effectuée avec du sang hyperagrégeant chez le rat de souche Brown Norway. La pression caudale, le volume cardiaque systolique, la fraction d’éjection, le débit cardiaque, le rythme cardiaque et la résistance périphérique à l’écoulement sanguin ont été observés non-intrusivement sur 19 jours suite à la transfusion. Les rats ont été sacrifiés plus d’un mois suivant la transfusion et une étude ex vivo de la réponse à deux agents dilatateurs (l’acétylcholine et le nitroprussiate de sodium) a été menée sur les artérioles mésentériques. Des variations des paramètres cardiovasculaires, soit le débit, le volume systolique et la résistance périphérique, ont été remarquées dans les trois premiers jours posttransfusion. Une résistance du muscle vasculaire lisse au monoxyde d’azote a été notée chez les rats transfusés au sang hyperagrégeant alors qu’aucune dysfonction endothéliale n’était apparente en réponse à l’acétylcholine. / The aim of this study was to evaluate the effects of an acute change in erythrocyte aggregation on cardiovascular parameters by exchanging one third of the blood volume with hyperaggregating blood in the Brown Norway rat model. Values of caudal pressure, systolic cardiac volume, ejection fraction, cardiac output, heart rate and peripheral resistance to blood flow were observed non-invasively over 19 days after transfusion. The rats were sacrificed after more than a month following the procedure and an ex vivo study in response to pharmacological agents (acetylcholine and sodium nitroprussiate) was performed on mesenteric arterioles. Variations in cardiac output, systolic volume and peripheral resistance were noted for the first three days post-transfusion. The vascular smooth muscles of rats transfused with the hyperaggregating erythrocytes seemed to have developed a resistance to nitric oxide but no endothelial dysfunction was observed in response to acetylcholine.