Abdominal manifestations associated with use of a surface-treated AN69 membrane and ACEI during haemodialysis

Sir, Dialyzer reactions are classified in two types: type A and type B. Type A, or ‘anaphylactoid’, reactions are mostly caused by leachable substances from the dialyzer (i.e. ethylene oxide) or by bacterial contamination. Type B reactions are mediated by complement activation and are becoming less frequent with the use of more biocompatible synthetic membranes. The anaphylactoid reaction seen when haemodialysed patients receive an angiotensin-converting enzyme inhibitor (ACEI), while using an AN69 dialyzer, is well described [ 1 , 2 ]. To our knowledge, however, there are only three cases of adverse events associated with ACEI and the surfaced-treated AN69 membrane. The first patient experienced an anaphylactoid reaction after a single dose of captopril [ 3 ]. The other two patients had a more subtle presentation, with abdominal pain and diarrhoea [ 4 ]. We report here on another patient who had intestinal manifestations and hypotension in the same context. An 81-year-old man with end-stage renal disease secondary to hypertensive nephrosclerosis has been on chronic haemodialysis since February 2006. He is dialysed for 4 h three times a week, with a synthetic polyarylethersulphone/polyamide membrane (Polyflux 17L, Gambro). He also suffers from atherosclerotic cardiac and vascular disease, congestive heart failure (left ventricular ejection fraction of 40%) and atrial fibrillation. His medication includes aspirin, warfarin, metoprolol, lisinopril, furosemide, erythropoietin, intravenous iron, allopurinol and clonazepam. The patient was taking a combination of hydralazine and nitrate, which was replaced by a small dose of lisinopril (2.5 mg once daily) shortly after he began haemodialysis. The patient underwent ophthalmic surgery in May 2006. His usual dialyzer was replaced by a surface-treated AN69 membrane (Nephral ST 400, Gambro) for the next dialysis treatments. On 15 May 2006, the patient presented with a hypotensive episode. His blood pressure was 114/64 just before the start of haemodialysis, and dropped to 82/39 about 1h 30 min later. Boluses of normal saline were given, but the dialysis had to be stopped because of persisting hypotension. The patient finally quit the dialysis unit with a blood pressure of 111/75. On the next session, two days later, he once again experienced a blood pressure drop from 116/69 to 86/48 in the first hour of dialysis. This time, however, he also complained of severe abdominal cramps and had massive diarrhoea. The session was stopped immediately, with symptoms resolving spontaneously. The dialyzer was changed back to Polyflux 17L at the next dialysis, with no recurrence of hypotension or intestinal symptoms. At the time, we did not link the ST-AN69 membrane to the patient's manifestations. On 23 and 25 October 2006, a Nephral ST 400 (from a different lot) was reintroduced because of a temporary contraindication to anticoagulation (fistulography with angioplasty). Less than 1 h after the beginning of the dialysis, abdominal pain and diarrhoea recurred. The patient had no hypotension this time. The surface-treated AN69 membrane was suspected to be responsible and the next haemodialysis was started with the patient's former dialyzer, with no other adverse event. Lisinopril was continued. The AN69 membrane has one of the highest electronegativity of all dialysis membranes, due to the methylsulphonate radicals. This electronegativity is known to enhance bradykinin production [ 5 , 6 ]. By preventing degradation of bradykinin, ACEI can raise bradykinin to potentially harmful levels (as much as 20–30-fold). Polyethyleneimine (PEI) is a polycationic saline solution used to coat the surface of AN69 membrane, making them less electronegative. This surface-treated membrane has been used safely in patients also receiving ACEI [ 7 ]. However, we found three cases of adverse events occurring in this setting that resolved after changing the dialyzer [ 3 , 4 ]. In our patient taking a small dose of ACEI, the recurrence of symptoms with rechallenge is also in favour of a dialyzer-related reaction. The proposed explanation was an imperfect covering of the negative charges on the membrane by PEI, which induces a conformational change in the Hageman factor. This facilitates the binding of Hageman factor and kininogen with prekallikrein, thus activating a reaction that leads to formation of bradykinins [ 3 , 5 ]. In conclusion, we suggest caution when using a surface-treated AN69 membrane in a patient who is also taking ACEI. A wide spectrum of hypersensitivity manifestations may occur, ranging from anaphylactoid reaction to mild abdominal pain or diarrhoea. The dialyzer should be replaced as soon as one suspects a hypersensitivity reaction associated to surface-treated AN69 membrane. Conflict of interest statement . None declared.

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