Hemodynamic effects of partial correction of chronic anemia by recombinant human erythropoietin in patients on dialysis.

Eighteen patients on chronic hemodialysis with renal anemia were treated with recombinant human erythropoietin (r-HuEPO). Hemodynamic parameters in the resting state were determined before and after successful treatment. Posttreatment cardiac index was decreased (3.3 v 2.8 L/min/m2), whereas diastolic blood pressure (72 v 79 mm Hg) and calculated peripheral resistance (2,230 v 2,860 dyne.cm.s-5) were increased significantly when compared with the pretreatment period. We conclude from our study that the increase of blood pressure as seen in patients on dialysis, who are effectively treated with r-HuEPO, is due to an increase in peripheral resistance. This increase overrules the decrease of cardiac index and might well be a result of peripheral vasoconstriction due to improved oxygen availability.

[Aerobic and anaerobic capacity of chronic hemodialysis patients under continuous therapy with recombinant human erythropoietin]. / Verhalten der aeroben und anaeroben Leistungsfähigkeit chronischer Hämodialysepatienten unter einer Dauertherapie mit rekombinantem humanem Erythropoietin.

In earlier studies we have shown that partial correction of anemia by recombinant human erythropoietin (r-HuEPO) already after 12 weeks results in a significant increase of exercise capacity in patients on chronic hemodialysis. As causative effect increased oxygen availability with improved oxygen delivery to the tissues was assumed. To elucidate the long-term effects of a partial correction of anemia with r-HuEPO on exercise capacity, oxygen uptake at maximum exercise and at the anaerobic threshold was measured by repetitive spiroergometry. Measurements were done before, 3 months and 6 months after initiation of r-HuEPO therapy. The results are summarized below: (table; see text) Our results show that a long-term improvement of peripheral oxygen availability leads to a further increase of anaerobic threshold in patients on chronic hemodialysis even without a further increase of hemoglobin levels and without exercise training. It appears that elimination of the chronic hypoxic condition results in a restoration of previously diminished mitochondrial enzymes in muscle, particularly for aerobic glycolysis. Besides acute improvement of aerobic and anaerobic exercise capacity, the long-term administration of r-HuEPO with its increased anaerobic threshold enhances the patients' everyday life working capacity.

Working capacity is increased following recombinant human erythropoietin treatment.

To investigate the effect of partial correction of anemia in patients maintained by chronic intermittent hemodialysis on aerobic and anaerobic working capacity, eight patients underwent a bicycle spiro-ergometry before and after treatment with recombinant human erythropoietin (r-HuEPO). the initial mean (+/- SD) hemoglobin value was 5.9 mg/dl +/- 0.61 and increased during treatment to 10.9 +/- 0.59 mg/dl, P less than 0.0001). This partial correction of anemia resulted in a significant increase of both oxygen uptake at the anaerobic threshold and peak peripheral oxygen uptake at subjective exhaustion (P less than 0.01 and P less than 0.0002, respectively). The increase in oxygen uptake corresponded to significant increases in Watts, both at the anaerobic threshold and at maximum workload (P less than 0.02 and P less than 0.0004). These data show that partial correction of renal anemia results in a significant increase of both exercise capacity and maximum work.

[Effectiveness of recombinant human erythropoietin in the treatment of transfusion-dependent anemia in patients on chronic dialysis]. / Wirksamkeit von rekombinantem humanem Erythropoietin in der Behandlung der transfusionsabhängigen Anämie chronischer Dialysepatienten.

Recombinant human erythropoietin (r-HuEPO) has recently become available for clinical trial and has been used for the first time in Austria for the treatment of transfusion dependent patients on chronic haemodialysis. Inclusion criteria into the study were baseline haemoglobin levels of less than or equal to 6 g/dl and transfusion requirements of greater than or equal to 1 unit of blood per month. r-HuEPO (CILAG/AMGEN/ORTHO) was administered intravenously 3 times weekly at the end of dialysis. The initial dose was 100 U/kg body weight at each administration and was increased by 25 U/kg if Hb levels failed to increase by greater than 5% of baseline at intervals of 3 weeks. All 9 patients studied showed an increase in Hb values to the desired value at least greater than or equal to 10 g/dl within 6 to 16 weeks and none of the patients required further blood transfusions. All patients reported subjective improvement of life quality and markedly increased working ability. Apart from minor episodes of bone pain and subfebrile temperatures after r-HuEPO administration no major side effects were noted. These preliminary results show that r-HuEPO (CILAG/AMGEN/ORTHO) is a safe and effective form of therapy for renal anaemia and one which opens new horizons in the management of patients on chronic haemodialysis.