Using AN69 ST membrane: A dialysis centre experience

H. Maheut and F. Lacour

Clinique de Champagne CHU de Reims Reims France

Sir,

The contact between blood and dialysis membrane can induce serious side-effects, mostly linked to hypersensitivity reactions (HSRs). These reactions are observed during the first minutes after the dialysis onset. Their clinical expression associates at least two of the following symptoms: thoracic oppression, nausea, vomiting, itching, severe hypotension and shock.

All types of membrane are concerned, but HSRs are more frequent and severe in patients treated simultaneously with the AN69 membrane and ACE inhibitors (ACEI) [1].

A prospective multicentre study conducted in 30 French dialysis units in 1993 showed a low prevalence: 33 HSRs for 122,694 dialysis sessions (0.03%) and the conclusion was reached that being treated with ACEI and AN69 membrane together, patients might develop HSRs at a fivefold higher risk than patients treated with the same ACEI and an another type of highly permeable dialysis membrane. Seventy-two percent of the HSRs were observed within only two units. The causes of this ‘Centre effect’ were not elucidated [2].

These accidents led nephrologists to avoid the prescription of ACEI together with AN69 membrane in dialysis patients.

HSR responds to an anaphylactoid mechanism: the contact phase activation which generates plasma bradykinin (BK), a powerful pro-inflammatory peptide. ACEI inhibit BK degradation and potentiate its accumulation [3].

Recent in-vitro experimental studies using miniaturized dialysers demonstrate the crucial role of physiochemical factors such as the plasma dilution and the pH values of the rinsing solution [4]. They stressed the pivotal role of the electronegativity of the membrane surface when placed in an acidic milieu. The more electronegative the membrane, the greater its ability to generate BK release at low pH. 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 (PEI) reduces the surface electronegativity avoiding the BK generation even at low pH [4].

We report here our 3 year experience with the use of a PEI-coated AN69 membrane in chronic dialysis patients.

Previously (March 1997), PEI treatment (9 mg/m2) was realized with the Crystal series (Plate dialyzers, Hospal-France) during the priming procedure through a specific device installed on the rinsing line, containing an adequate PEI quantity. Starting in September 1999, membrane treatment took place during the manufacturing process by spraying PEI at the same concentration (9 mg/m2) (Crystal 4000 ST).

From 15 March 1997 to 31 July 2000, 56 patients were dialyzed with PEI-coated AN69 membrane. A total of 10630 dialysis sessions were performed. Seventeen of the 56 patients were simultaneously treated with ACEI at various doses, for a total of 3400 dialysis sessions.

No HSR was observed in these patients, whether receiving ACEI or not. One ACEI-treated female patient having developed a moderate degree of HSR at the start of her first dialysis session caught our attention. It finally appeared that the PEI adjunction had been unfortunately omitted.

In 1990 in our dialysis centre a very high incidence of HSR was observed in patients treated with the association of AN69 and ACEI namely 19/1000 dialysis sessions [5], and this combination was no longer used until March 1997.

In conclusion, the AN69 ST membrane has been used safely in ACEI-treated patients, even with three of the 17 patients having suffered in the past one or more HSR when dialysed with the non-treated AN69. These three patients had given their informed consent to the change of the membrane. Though retrospective in nature, our clinical experience tends to confirm that HSRs can be efficiently prevented using PEI-grafted AN69 membrane. Prospective studies are needed to definitely prove the potential benefit of this modified membrane compared with other highly permeable membranes.

References

  1. Tielemans C, Madhoun P, Lenaers M, Schandene L, Goldman M, Vanherweghem, JL. Anaphylactoid reactions during hemodialysis on AN 69 membrane in patients receiving ACE inhibitors. Kidney Int1990; 38: 982–984[ISI][Medline]
  2. Simon P, Potier J, Thebaud HE. Facteurs de risque des réactions aiguës d'hypersensibilité en hémodialyse: enquête prospective multicentrique sur six mois dans Ouest de la France. Nephrologie1996; 17: 163–170[ISI][Medline]
  3. Blais C Jr, Marc-Aurele J, Simmons WH, Loute G, Thibault P, Skidgel RA, Adam A. Des-Arg9-bradikinin metabolism in patients who presented hypersensitivity reactions during hemodialysis: Role of serum ACE and aminopeptidase P. Peptides1999; 20: 421–430[ISI][Medline]
  4. 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]
  5. Lacour F, Maheut H. Membrane AN 69 et inhibiteurs de l'enzyme de conversion: Prévention des chocs anaphylactoïdes par le rinçage alcalin? Nephrologie1992; 13: 135–136[ISI][Medline]