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

Abstract

Use of recombinant human erythropoietin (rHuEpo) in patients with end-stage renal disease (ESRD) improves anemia and reduces the need for blood transfusions. However, one third of patients on rHuEpo develop hypertension, aggravation of preexistent hypertension, or other complications. Nitric oxide (NO) plays a role in blood pressure (BP) regulation. Whether rHuEpo treatment in ESRD is accompanied by alterations in NO production was explored in patients undergoing hemodialysis. Of 121 consecutive patients in a hemodialysis clinic, 107 were treated with rHuEpo and 14 were untreated. Plasma was collected before and after hemodialysis for quantification of nitrite and nitrate (NOx). Findings were correlated with various routinely monitored parameters. Predialysis NOx levels were lower in the treated than the untreated group; postdialysis NOx levels were virtually the same. Thus, the change was less in the treated group. Urea reduction ratios (URR) and ultrafiltrate volumes were similar. The mean predialysis systolic BP was higher in the treated group than in the untreated group. The 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 107 treated patients, 12 had an increased postdialysis NOx without differences in ultrafiltrate volumes or URR. This group had higher total serum calcium levels, faster pulses, and greater BP reductions than other treated patients. No difference was found in the use of calcium-channel blockers and serum phosphorus and intact parathyroid hormone concentrations did not differ significantly among these groups. Intermittently hemodialyzed ESRD patients treated with rHuEpo accumulate less NOx in the plasma before dialysis but generate more NOx during dialysis than untreated patients. About 11% of treated patients generated excessive amounts of NOx, thereby maintaining plasma concentrations at the predialysis level or higher. This group experienced significant hemodynamic consequences characteristic of the excessive action of NO.