Biphasic changes in nitric oxide generation in hemodialyzed patients with end-stage renal disease treated with recombinant human erythropoietin

Background: Use of recombinant human erythropoietin (rHuEpo) in patients wi th end-stage renal disease (ESRD) improves anemia and reduces the need for blood transfusions. However, one third of patients on rHuEpo develop hypert ension, aggravation of preexistent hypertension, or other complications. Ni tric oxide (NO) plays a role in blood pressure (BP) regulation. Whether rHu Epo treatment in ESRD is accompanied by alterations in NO production was ex plored in patients undergoing hemodialysis. Methods: Of 121 consecutive pat ients in a hemodialysis clinic, 107 were treated with rHuEpo and 14 were un treated. Plasma was collected be:fore and after hemodialysis for quantifica tion of nitrite and nitrate (NOx). Findings were correlated with various ro utinely monitored parameters. Results: Predialysis NOx levels were lower in the treated than the untreated group; postdialysis NOx levels were virtual ly the same. Thus, the change was less in the treated group. Urea reductio n ratios (URR) and ultrafiltrate volumes were similar. The mean predialysis systolic BP was higher in the treated group than in the untreated group. T he dose of rHuEpo did not correlate with the plasma NOx or the predialysis BPs. No correlation was found between NOx levels and Hb or gender. Of the 1 07 treated patients, 12 had an increased postdialysis NOx without differenc es in ultrafiltrate volumes or URR. This group had higher total serum calci um levels, faster pulses, and greater BP reductions than other treated pati ents. No difference was found in the use of calcium-channel blockers and se rum phosphorus and intact parathyroid hormone concentrations did not differ significantly among these groups. Conclusions: Intermittently hemodialyzed ESRD patients treated with rHuEpo accumulate less NOx in the plasma before dialysis but generate more NOx during dialysis than untreated patients. Ab out 11% of treated patients generated excessive amounts of NOx, thereby mai ntaining plasma concentrations at the predialysis level or higher. This gro up experienced significant hemodynamic consequences characteristic of the e xcessive action of NO.