Anaphylactoid reaction induced by ACEI during haemodialysis with a surface-treated AN69 membrane

Ramón Peces

Nephrology Service, Hospital Universitario La Paz, Madrid, Spain Email: rpeces{at}hulp.insalud.es

Sir,

Anaphylactoid reactions during haemodialysis using AN69 membrane in patients receiving angiotensin-converting enzyme inhibitors (ACEI) are well recognized [1]. However, to our knowledge, anaphylactoid reactions induced by ACEI during haemodialysis with a surface-treated AN69 membrane have not been reported so far. We report on a patient who experienced an anaphylactoid reaction while dialysing on surface-treated AN69 membrane and received a single dose of captopril.

Case

A 49-year-old male with end-stage renal disease secondary to familial focal segmental glomerulosclerosis and factor V Leiden was on regular haemodialysis since November 2000. In the past, he had received treatment with ACEI to decrease proteinuria. He was receiving 4 h of dialysis three times a week using a surface-treated AN69 membrane (Nephral ST® 500) dialyser sterilized with steam. The dialysate calcium concentration was 1.5 mmol/l. The patient's medication comprised nifedipine LA 60 mg od, ranitidine 150 mg od, aspirin 200 mg od, ticlopidine 250 mg od, calcitriol 0.25 µg od, calcium carbonate 3 bid and s.c. Epo 3000 U/week. He had hypertension and gained excessive weight in between dialysis sessions. On 19 December 2001, ~1 h into haemodialysis, he developed headache and his blood pressure was 191/110 mmHg. An oral dose of 25 mg captopril was given and ~30 min later he experienced itching, flushing, tongue and throat swelling, breathlessness, thoracic oppression, nausea and vomiting. His blood pressure was 175/94 mmHg and his pulse rate was 100 beats/min. A clinical diagnosis of acute hypersensitivity reaction due to the AN69–ACEI interaction was made, the haemodialysis session was stopped and the patient was immediately taken off the machine. Intravenous methylprednisolone 80 mg and dexchlorpheniramine 5 mg was given, and the patient's condition improved rapidly. The dialyser was changed to a high flux polysulfone membrane dialyser (Hemoflow HF80S®) and he continued his haemodialysis session without any further problems.

Anaphylactoid reaction in patients who dialyse on AN69 whilst taking ACEI is well recognized [1]. This reaction occurs in the first 10–20 min of the dialysis session. Underlying reasons are mainly the induction of bradykinin release due to the negatively charged membrane and the reduced degradation of bradykinin due to ACE inhibition [13]. The AN69 membrane, due to its methylsulphonate radicals, exhibits the highest surface electronegativity of all dialysis membranes currently used. Coating the AN69 membrane with a polycationic saline solution reduces surface electronegativity, thereby avoiding the generation of bradykinin [4]. The use of surface-treated AN69 membrane may prevent hypersensitivity reactions during haemodialysis. Indeed, the surface-treated AN69 membrane has been used safely in ACEI-treated patients [4]. Our patient developed an anaphylactoid reaction despite the use of a surface-treated AN69 membrane. He presented the reaction later whilst on haemodialysis when a single dose of captopril was administered. It is possible that this is related to the dose and timing of the intake of the ACEI in relationship to the start of the dialysis session. We suggest that there might be an activation of the Hageman factor by the incompletely neutralized negative charge of the AN69 membrane, leading to persisting bradykinin synthesis. In the absence of ACEI plasma, bradykinin levels increased only moderately, and clinically the patient was free of symptoms. However, once kininase II, which is identical with converting enzyme, was blocked by captopril, plasma bradykinin levels increased markedly and the patient suffered from a severe reaction. Since some of the bradykinin effects are mediated by nitric oxide, aspirin treatment might potentiate these effects.

In addition to these variable exogenous factors, interindividual differences in bradykinin generating and degrading capacities might play a role. Variable tissue and circulating bioactivity of kallikrein inhibitors may lead to differences in bradykinin generation. A decrease of serum aminopeptidase P activity might also play a role [5]. It is of course possible that different mechanisms are responsible for the hypersensitivity reaction [5,6]. Thus, the fact that the patient was given ACEI in the past does not exclude completely a reaction type angioedema or a true allergic reaction to the drug. In conclusion, prospective studies are needed to confirm the safety of this modified membrane. We therefore recommend caution in using ACEI in patients using surface-treated AN69 membrane dialysers.

References

  1. Verresen L, Fink E, Lemke HD, Vanrenterghem Y. Bradykinin is a mediator of anaphylactoid reaction during hemodialysis with AN69 membrane. Kidney Int1994; 45: 1497–1503[ISI][Medline]
  2. Renaux JL, Thomas M, Crost T, Loughraieb N, Vantard G. Activation of the kallikrein-kinin system in hemodialysis. Role of membrane electronegativity, blood dilution and pH. Kidney Int1999; 55: 1097–1103[ISI][Medline]
  3. Krieter DH, Grude M, Lemke HD et al. Anaphylactoid reaction during hemodialysis in sheep are ACE inhibitor dose-dependent and mediated by bradykinin. Kidney Int1998; 53: 1026–1035[ISI][Medline]
  4. Maheut H, Lacour F. Using AN69 ST membrane: a dialysis centre experience. Nephrol Dial Transplant2001; 16: 1519–1520[Free Full Text]
  5. Blais C Jr, Marc-Aurele J, Simmons WH et al. Des-Arg9-bradykinin metabolism in patients who presented hypersensitivity reactions during hemodialysis: role of serum ACE and aminopeptidase P. Peptides1999; 20: 421–430[ISI][Medline]
  6. John B, Anijeet HKI, Ahmad R. Anaphylactic reaction during hemodialysis on AN69 membrane in a patient receiving angiotensin II receptor antagonist. Nephrol Dial Transplant2001; 16: 1955–1956[Free Full Text]




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