Verresen L, Fink E, Lemke H D, Vanrenterghem Y
Department of Nephrology, University of Leuven, Belgium.
Kidney Int. 1994 May;45(5):1497-503. doi: 10.1038/ki.1994.195.
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.
类过敏反应（AR）是血液透析最可怕的并发症。最近，有报道称在接受ACE抑制剂治疗的患者使用AN69膜进行透析期间，AR的发生率很高。在12例使用AN69进行透析且发生AR的患者发病时，检测了其血浆C3a、组胺和缓激肽水平。我们还研究了10例使用四种不同膜进行透析且无症状的患者的缓激肽生成情况。在发生AR时研究的12例患者中，均未表现出补体过度激活或组胺释放。相反，在检测缓激肽的所有9例患者中，均观察到血浆缓激肽水平很高（2392±53 fmol/ml；平均值±标准误）。1例患者即使未服用ACE抑制剂，在AN69膜上也连续发生了两次过敏反应。两次发作时缓激肽水平均很高（分别为5280和10467.7 fmol/ml）。此外，该患者在使用其他膜进行透析时无症状，缓激肽水平正常（123.4 fmol/ml）。与其他膜如铜仿膜（5.1±7.3）、血仿膜（17.2±6.3）和聚砜膜（39.7±6.6）相比，在无症状透析期间，AN69引发的缓激肽生成也显著更高（327.6±18 fmol/ml；平均值±标准误），这一观察结果进一步证实了膜类型在AR中的作用。我们的研究结果强烈表明，缓激肽是使用AN69膜进行血液透析期间AR的主要介质。据我们所知，这是首次有数据支持缓激肽在类休克症状中具有更普遍作用这一假说。此外，缓激肽生成必须被视为体外治疗生物相容性的一个新标志物。
