title: Biphasic changes in nitric oxide generation in hemodialyzed patients with end-stage renal disease treated with recombinant human erythropoietin.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  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. 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.
authors.affiliation: Department of Pediatrics, University of Tennessee, Memphis 38163, USA. eskang@pol.net
authors.forename: E S
authors.initials: ES
authors.lastname: Kang
authors.forename: Y B
authors.initials: YB
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Cardenas
authors.forename: M T
authors.initials: MT
authors.lastname: Tevlin
authors.forename: S
authors.initials: S
authors.lastname: Mishra
authors.forename: S R
authors.initials: SR
authors.lastname: Acchiardo
mesh_terms: D001794:Blood Pressure; D001835:Body Weight; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000096:biosynthesis / Q000097:blood*; D009573:Nitrites / Q000097:blood; D011994:Recombinant Proteins; D006435:Renal Dialysis
chemical_list: D009566:Nitrates; D009573:Nitrites; D011994:Recombinant Proteins; D004921:Erythropoietin; D009569:Nitric Oxide