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

Abstract

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.

Kinetics of Bradykinin Levels during and after Leucocyte Filtration of Platelet& ;Concentrates

“…We report a high interindividual variation in the ability to generate bradykinin, which is in line with the experience from other clinical settings [23]. In addition, we also noted a high donation-to-donation variation within the same individual in a single experiment.…”

International Union of Pharmacology. XLV. Classification of the Kinin Receptor Family: from Molecular Mechanisms to Pathophysiological Consequences

“…Patients experiencing hypersensitivity to dialysis membranes have been shown to have increased plasma levels of BK (Schaefer et al, 1993;Verresen et al, 1994). Lower serum aminopeptidase P activity differentiated dialysis patients who had experienced a hypersensitivity reaction to the negatively charged membrane from patients who had not experienced a reaction (Blais et al, 1999).…”

Is Platelet-Activating Factor Produced during Hemodialysis with AN-69 Polyacrylonitrile Membrane?

“…To conclude: (a) Since in the early 1990s, a number of studies have concluded an increased frequency of anaphylactoid reactions in ACEI-treated hemodialyzed patients with AN-69 membrane [50, 51, 52, 53]; for these reactions the pathogenic agent was assumed to have increased the secretion of bradykinin (a tissue peptide hormone with a variety of direct or indirect – due to induction of the secondary mediators release – effects, which included vasodilation and bronchoconstriction) from the membrane by activation of Hageman factor [54, 55, 56, 57, 58]. (b) PAF synthesis and secretion are indeed induced by AN-69 membrane and as it is a very active vasodilator and bronchoconstrictor agent, it could also be implicated in the pathogenesis of acute anaphylactic type reaction of HD [7, 59].…”