Mechanism of the depressor effect of recombinant human erythropoietin in anemic patients undergoing chronic hemodialysis

A depressor effect of recombinant human erythropoietin (EPO) has been noted in some anemic patients with chronic renal failure undergoing maintenance hemodialysis. In order to clarify the mechanism of the depressor effect of EPO, changes in blood pressure, cardiac function and plasma vasoactive substances were evaluated at, before and after EPO therapy. Twenty-eight dialysed patients with renal anemia (hematocrit value≤23.5%) were treated with EPO to maintain a hematocrit value between 25 and 30%. Before and after EPO administration for 12 months, blood pressure, heart rate, body weight, blood count, echocardiography, plasma adrenaline (pNA), plasma renin activity (PRA), angiotensin II (A-II) and atrial natriuretic peptide (ANP) were determined. Significant depressor effects of EPO were found in 4 patients (DP group) but not in the other 24 (non-DP group). There were no differences in the severity of anemia between these two groups over the 12 month period. Heart rate and body weight were not changed by EPO in either group. Left atrial dimension and left ventricular dimension did not differ between the DP and non-DP groups. Before EPO administration, the left ventriculer ejection fraction was higher in the DP than in the non-DP group. Left ventricular stroke volume (SV) and cardiac output (CO) showed significant decreases or a tendency to decrease with EPO administration, especially in the DP group. As a result, significant positive correlations were found between changes in blood pressure and SV, and blood pressure and CO only in the DP group. No significant difference was found in total peripheral resistance between the DP and non-DP groups. There were no differences in pNA, PRA, A-II and ANP between the two groups. In conclusion, correction of the high cardiac output state may be one of the mechanisms mediating the deprssor effect of EPO.