Des-Arg 9-bradykinin metabolism in patients who presented hypersensitivity reactions during hemodialysis: role of serum ACE and aminopeptidase P

Abstract

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 t 1/2 of BK was found between the patient groups. However, the t 1/2 of generated des-Arg 9-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 t 1/2 of both BK and des-Arg 9-BK in both groups. There was no significant difference between the groups with respect to the t 1/2 of BK, but there was a significantly greater increase (3.8-fold) in the t 1/2 of des-Arg 9-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 ( r 2 = 0.6271; P < 0.00005) could be calculated between APP activity and des-Arg 9-BK t 1/2. 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-Arg 9-BK may lead to the accumulation of this B 1 agonist that could be responsible, at least in part, for the signs and symptoms of HSR.