Regional Renal Unit Royal Liverpool University Hospital Liverpool, UK
Sir,
Anaphylactic reactions during haemodialysis using AN69 membrane in patients receiving angiotensin-converting enzyme inhibitors (ACE-I) are well recognized [1]. However, anaphylactic reactions are rare in patients on angiotensin II receptor antagonists with AN69 dialysers. To our knowledge, there are only two reported cases of possible anaphylactoid reactions with the angiotensin II receptor antagonist, losartan [2]. We report a patient who had anaphylactic reaction while dialysing on AN69 and receiving losartan.
Case. A 43-year-old male, with end-stage renal disease secondary to anti-GBM disease was on regular haemodialysis. He was receiving 4-h dialysis three times a week and was using a Haemophan® membrane (COBE 400) dialyser. His medications were nifedepine LA 30 mg once daily, losartan 25 mg once daily, azathioprine 50 mg once daily, prednisolone 12.5 mg once daily, ranitidine 150 mg bid, aluminium hydroxide capsules 3 tid, calcium carbonate 3 bid, erythropoietin 2000 units s/c 3 days per week and iron saccharide 100 mg twice monthly. He was anuric and gained excessive weight in between dialysis. The urea removal rate (URR) was 46.79%. Since he was not being adequately dialysed, the dialyser was changed to AN69 (Filtral® 2800) but the other dialysis parameters were unchanged. About an hour into the first dialysis on the AN69, he developed breathlessness and became agitated with profuse sweating. He denied any chest pain. His pulse rate was 100 per minute and blood pressure was 202/108 mmHg. Chest examination revealed scattered basal crepitations. A clinical diagnosis of acute allergic reaction to the dialyser membrane was made and he was immediately taken off the machine. Intravenous hydrocortisone 200 mg along with chlorpheniramine 4 mg was given and his condition rapidly improved. The patient refused a trial of dialysis on AN69 after stopping losartan. Hence he was put back onto a Haemophan HG® membrane dialyser but with a higher surface area (COBE 600). The dialysis has since then remained uneventful. He has remained stable and his URR is now 65.38%.
Comment. The first use reactions are allergic in nature, which occurs with the use of a fresh dialyser. These have been linked to sterilant ethylene oxide and this has been overcome by gamma sterilization. Anaphylactic reactions in patients who dialyse on AN69 whilst taking ACE-I is well recognized [1]. The risks of reaction vary from unit to unit and even in the same unit only some patients develop reactions raising the possibility of individual susceptibility. Even the same patient does not always develop reactions. This lack of reproducibility should point towards a multifactorial aetiology. It has been hypothesized that bacterial pathogens are the initiating factors and these reactions were potentiated or amplified in patients on ACE-I [1]. Some researchers have suggested that high bradykinin levels were responsible for the anaphylactoid reactions possibly due to synthesis of bradykinin by the AN69 membrane along with reduced degradation by the presence of ACE-I [3]. Others have demonstrated a higher bradykinin level at the outlet of the AN69 membrane dialyser when compared to the inlet concentration [4]. However, Wakasa et al. did not find any significant difference in bradykinin levels in the two groups of patients on AN69 with and without ACE-I. It should be noted that none of the patients in this report developed any reactions during dialysis. They suggested that there might be an activation of the Hageman factor by the negative charge of the AN69 membrane leading to increased bradykinin synthesis [5]. Anaphylaxis has commonly been described with AN69 dialyser in ACE-I (i.e. captopril and enalapril) treated patients. These drugs alter bradykinin levels by virtue of their inhibition of angiotensin-converting enzyme. However, angiotensin II receptor antagonists have no effect on bradykinin metabolism. Our patient developed the anaphylactic reaction whilst on losartan.
In conclusion we therefore recommend caution in using angiotensin II receptor antagonists in patients using AN69 membrane dialysers.
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