Bradykinin is a mediator of anaphylactoid reactions during hemodialysis with AN69 membranes

Bradykinin is a mediator of anaphylactoid reactions during
hemodialysis with AN69 membranes. Anaphylactoid reactions (AR) are
the most feared complications of hemodialysis. Recently, a high
incidence of AR has been reported during dialysis with AN69
membranes in patients treated with ACE inhibitors. Plasma levels of
C3a, histamine and bradykinin were measured in 12 patients at the
onset of AR during dialysis with AN69. We also investigated
bradykinin generation in 10 symptom-free patients dialyzed with
four different membranes. None of the 12 patients studied during AR
displayed excessive complement activation or histamine release. In
contrast, high bradykinin plasma levels (2392 53 fmol/ml; mean sem)
were observed in all nine patients of whom bradykinin was measured.
One patient developed two consecutive episodes of hypersensitivity
on AN69 membranes even without taking ACE inhibitors. Bradykinin
levels were high in both episodes (5280 and 10467.7 fmol/ml).
Furthermore, this patient showed no symptoms and normal bradykinin
levels (123.4 fmol/ml) when dialyzed with other membranes. The role
of the membrane type in the AR is further substantiated by the
observation that AN69 also provoked a significantly higher
bradykinin generation (327.6 18 fmol/ml; mean SEM) during
symptom-free sessions compared to other membranes like CuprophanR
(5.1 7.3), HemophanR (17.2 6.3) and PolysulfoneR (39.7 6.6). Our
findings strongly suggest that bradykinin is the principal mediator
of AR during hemodialysis with AN69 membranes. To our knowledge it
is the first time that data support the hypothesis of a more
general role of bradykinin in shock-like symptoms. Furthermore,
bradykinin generation must be regarded as a new marker of
biocompatibility of extracorporeal treatments.