Kinin-dependent hypersensitivity reactions in hemodialysis: metabolic and genetic factors.
2006
Although the association of angiotensin I-converting enzyme inhibitors (ACEis) with a negatively charged membrane is thought to be responsible for hypersensitivity reactions (HSRs) during hemodialysis, we hypothesize that these complications are due to changes in plasma aminopeptidase P (APP) activity and genotype. To test this hypothesis, we measured plasma APP activity in 14 patients who suffered HSR (HSR+) while dialyzed with an AN69 membrane and simultaneously treated with an ACEi. APP activity was also studied in a control group ( n =39) dialyzed under the same conditions, but who did not suffer any side effect (HSR-). We found significantly decreased plasma APP activity ( P =0.013) in HSR+ subjects as well as altered degradation of endogenous des-Arginine 9 -bradykinin, with a significantly lower β value ( P P XPNPEP2 locus was a significant predictor of APP activity in the 39 HSR- controls ( P =0.029). Furthermore, a recessive genetic model for the A allele disclosed a significant difference in mean APP activity by genotype ( P
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