Des-Arg9-bradykinin metabolism in patients who presented hypersensitivity reactions during hemodialysis: role of serum ACE and aminopeptidase P

Peptides. 1999;20(4):421-30. doi: 10.1016/s0196-9781(99)00020-0.


Bradykinin (BK) has been proposed as the principal mediator of hypersensitivity reactions (HSR) in patients dialyzed using negatively charged membranes and concomitantly treated with angiotensin-converting enzyme (ACE) inhibitors. We investigated the metabolism of exogenous BK added to the sera of 13 patients dialyzed on an AN69 membrane with a history of HSR (HSR+ patients) and 10 others who did not present such a reaction (HSR- patients) while dialyzed under the same conditions. No significant difference in the t1/2 of BK was found between the patient groups. However, the t1/2 of generated des-Arg9-BK was significantly increased (2.2-fold) in HSR+ patients compared to HSR-subjects. Preincubation of the sera with an ACE inhibitor (enalaprilat) significantly increased the t1/2 of both BK and des-Arg9-BK in both groups. There was no significant difference between the groups with respect to the t1/2 of BK, but there was a significantly greater increase (3.8-fold) in the t1/2 of des-Arg9-BK in HSR+ patients compared to HSR-subjects. The level of serum aminopeptidase P (APP) activity showed a significant decrease in the HSR+ sera when compared to HSR-samples. In HSR- and HSR+ patients, a significant inverse relation (r2 = 0.6271; P < 0.00005) could be calculated between APP activity and des-Arg9-BK t1/2. In conclusion, HSR in hemodialyzed patients who are concomitantly treated with a negatively charged membrane and an ACE inhibitor can be considered as a multifactorial disease in that a decreased APP activity resulting in reduced degradation of des-Arg9-BK may lead to the accumulation of this B1 agonist that could be responsible, at least in part, for the signs and symptoms of HSR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins
  • Acrylonitrile / analogs & derivatives
  • Aged
  • Aminopeptidases / blood*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Bradykinin / analogs & derivatives*
  • Bradykinin / pharmacokinetics
  • Bradykinin / pharmacology
  • Enalaprilat / adverse effects*
  • Female
  • Humans
  • Hypersensitivity / drug therapy
  • Hypersensitivity / metabolism*
  • Lysine Carboxypeptidase / metabolism
  • Male
  • Membranes, Artificial
  • Middle Aged
  • Peptidyl-Dipeptidase A / blood*
  • Receptor, Bradykinin B1
  • Receptors, Bradykinin / agonists
  • Renal Dialysis / adverse effects*


  • Acrylic Resins
  • Angiotensin-Converting Enzyme Inhibitors
  • Membranes, Artificial
  • Receptor, Bradykinin B1
  • Receptors, Bradykinin
  • bradykinin, des-Arg(9)-
  • AN-69
  • Aminopeptidases
  • X-Pro aminopeptidase
  • Peptidyl-Dipeptidase A
  • Lysine Carboxypeptidase
  • Enalaprilat
  • Acrylonitrile
  • Bradykinin