Kinins and pseudo-allergic reactions

Several mediators can be involved in angioedema and cardiopulmonary-bypass-induced hypotension without a true immune allergic reaction. In the last years, we have evaluated the kinin system in patients with angioedema related to the therapy with angiotensin converting enzyme (ACE) inhibitors in comparison with normal subjects, patients with angioedema due to C1-inhibitor deficiency and patients with angioedema that responded to antihistamines. Bradykinin plasma levels were high in patients with ACE inhibitor related angioedema and patients with angioedema due to C1-inhibitor deficiency whereas they were normal in patients with angioedema that responded to antihistamines. Aminopeptidase P, an enzyme which besides ACE catabolizes bradykinin, was low in patients with ACE inhibitor related angioedema. Kinin evaluation has been also performed in patients undergoing cardiopulmonary bypass for cardiac surgery showing that during cardiopulmonary bypass plasma bradykinin increased and mean arterial pressure fell. At the end of the procedure both bradykinin and blood pressure returned to baseline. Here we applied a multivariate statistical approach to the kinetic parameters of the metabolism of endogenous kinins in 37 hypertensive patients with a history of angioedema during ACE inhibitor treatment and in 39 hypertensive patients who had never had ACE inhibitor-associated side-effects. It was possible to predict ACE inhibitor-associated angioedema with two parameters characterizing the metabolism of des-Arg9-bradykinin: the shape parameter  (p=0.0001) and the speed of the degradation (p=0.035). The statistical test showed a sensitivity of 81% and a specificity of 59%. In conclusion, bradykinin can be involved in conditions mimicking an allergic reaction like angioedema or cardiopulmonary-bypass-induced hypotension. The development of the study of kinin catabolism could provide a useful tool to predict ACE inhibitor-related angioedema.