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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 10  |  Issue : 2  |  Page : 282-284

First-use hypersensitivity reactions during hemodialysis


Department of Anesthesiology and Perioperative Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA

Date of Submission12-Oct-2022
Date of Acceptance12-Nov-2022
Date of Web Publication23-Dec-2022

Correspondence Address:
Mafdy N Basta
1120 15th Street, Augusta, GA 30912
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/amhs.amhs_236_22

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  Abstract 


Hypersensitivity reactions during hemodialysis result from the interaction between blood constituents and the hemodialysis membrane. Different types of membrane materials, including cellulose, substituted cellulose, or synthetic noncellulose, are used in dialyzers' manufacture which can affect the frequency and type of reaction seen. Two types of reactions, classified as Type A and Type B, have been described. Type A reaction is far less common but more severe than Type B. The following is a case of Type A reaction in a 63-year-old Caucasian male who had his first hemodialysis prescribed with a synthetic noncellulose membrane. His hemodialysis session was aborted and the reaction was successfully managed. Subsequent dialysis sessions were performed, uneventfully, with a substituted cellulose membrane. This case illustrates the importance of remaining vigilant and cognizant of the possibility of hypersensitivity reactions to hemodialysis membranes, as some of the reactions could be potentially life-threatening.

Keywords: Cellulose triacetate, hemodialysis membranes, hypersensitivity reactions, polysulfone


How to cite this article:
Basta MN. First-use hypersensitivity reactions during hemodialysis. Arch Med Health Sci 2022;10:282-4

How to cite this URL:
Basta MN. First-use hypersensitivity reactions during hemodialysis. Arch Med Health Sci [serial online] 2022 [cited 2023 Jan 31];10:282-4. Available from: https://www.amhsjournal.org/text.asp?2022/10/2/282/364964




  Introduction Top


Hemodialysis membranes reactions were initially attributed to the use of bio-incompatible, complement-activating dialyzer membranes, hypoxia-inducing acetate-containing dialysate, and ethylene-oxide sterilization of dialyzers that caused immunoglobulin E-mediated hypersensitivity. However, even in the current era, in which biocompatible dialyzers are being used, bicarbonate has replaced acetate as a dialysate buffer, and ethylene oxide sterilization has largely been abandoned, occasional cases of acute dialyzer reactions continue to be reported.


  Case Report Top


The patient was a 63-year-old Caucasian male that underwent radical cystectomy with ileal conduit for bladder cancer and right radical nephrectomy for kidney cancer. Home medications included apixaban (for lower extremity deep venous thrombosis), rosuvastatin, omeprazole, and tramadol (as needed for pain). The patient was discharged home on postoperative day 7 but was readmitted to the hospital on postoperative day 14 for sepsis and acute kidney injury (AKI). The patient was transferred to the surgical intensive care unit for further management. Following a lack of adequate improvement with conservative management, the patient was started on hemodialysis on day 1 of hospital readmission. The dialysis treatment was prescribed with Optiflux 180 NR [Figure 1], a synthetic noncellulose polysulfone, electron beam sterilized, membrane (Fresenius Medical Care North America, Waltham, MA). Within few minutes of starting the dialysis, the patient developed severe flushing of the face and chest, along with diaphoresis, tachycardia, desaturation, and generalized shaking. No fever, dyspnea, or hypotension was reported. No wheezing was detected on examination. Type A hypersensitivity reaction to the dialyzer membrane was suspected and the dialysis treatment was immediately stopped. The patient was treated with intravenous antihistamines and steroids, with a resolution of symptoms within few minutes. Relevant laboratory values, including eosinophil count, were within normal limits. Next day, the patient was premedicated with antihistamines and steroids and the dialysis was prescribed with Nipro Cellentia 17H dialyzer [Figure 2], a substituted cellulose triacetate, gamma radiation sterilized, membrane (Nipro North America, Bridgewater, NJ). No further reactions were reported. Subsequent dialysis treatments were all accomplished using the Nipro dialyzer and all were uneventful. Following management of sepsis and resolution of AKI, the patient was discharged home and instructed to follow-up as scheduled.
Figure 1: OptiFlux F180 NR dialyzer

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Figure 2: Nipro Cellentia-17H dialyzer

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  Discussion Top


Hypersensitivity reactions during hemodialysis result from the interaction between blood constituents and the hemodialysis membrane Two types of reactions, classified as type A and type B, have been described.[1] Type A reaction is far less common but more severe than type B. These reactions were grouped in the past under the term “first-use syndrome” because they primarily occurred with new dialyzers.

Different types of membranes materials, including cellulose, substituted cellulose, or synthetic noncellulose, are used in dialyzers' manufacture which can affect the frequency and type of reaction seen.

Cellulose membranes, polysaccharide-based membranes with abundant free hydroxyl groups, are primarily manufactured as cuprophan, and generally considered bioincompatible. Substituted cellulose membranes are obtained by the substitution of a material (e.g., acetate) to the free hydroxyl group. Biocompatibility ranges from relatively bioincompatible (as with cellulose acetate) to extremely biocompatible (as with cellulose triacetate). Synthetic noncellulose membranes (e.g., polysulfone, polyacrylonitrile [PAN], acrylonitrile-sodium methallyl sulfonate [AN-69]) have a higher permeability and are more biocompatible than the cellulose membranes.

Type A reactions are estimated to occur in approximately 4 of every 100,000 dialysis treatments.[1],[2] They typically occur within 30 min of starting the dialysis treatment. Symptoms range from mild (e.g., itching, burning sensation at the access site, urticaria, flushing, cough, sneezing, wheezing, abdominal cramps, diarrhea, headache, back and chest pain, nausea, vomiting, fever, and chills) to severe (e.g., dyspnea, hypotension, angioedema, and cardiac arrest). Some reactions may present as anaphylactic shock, mediated by immunoglobulin E, while others may be anaphylactoid in nature. Patients with an allergic diathesis and eosinophilia appear to be predisposed to this type of reaction.

Some anaphylactic type A reactions were related to the use of ethylene oxide, which was used to sterilize hollow fiber dialyzers.[3] Reactions to ethylene oxide occurred exclusively during the first use, usually when there has been inadequate rinsing of the dialyzer before use. Immunoglobulin E antibodies directed against ethylene oxide were present in some cases, particularly those with more severe reactions. Other substances that act as haptens, including, fomaldehyde,[4] latex,[5] chlorhexidine, intravenous iron, erythropoiesis-stimulating agents, and heparin, have also been associated with type A reactions.

A high incidence of anaphylactoid reactions is also seen when angiotensin-converting enzyme (ACE) inhibitors are used in patients treated with high-flux hemodialysis using acrylonitrile-sodium methallyl sulfonate (AN-69) dialyzers.[6] These membranes appear to act by increasing the rate of bradykinin generation, the inactivation of which is decreased in the presence of ACE inhibitors.

In recent years, an increased number of reports focused on hypersensitivity reactions to polysulfone membrane dialyzers;[7],[8],[9],[10] replacement of the dialysis membrane by a different one, usually cellulose triacetate, was associated with the disappearance of symptoms.[7],[8]

Rarely, Type A reactions are seen with reused dialyzers. No association was found with the disinfectant, the reprocessing method (manual or automated), or type of dialysate (bicarbonate or acetate). Multivariate analysis showed an increased risk with the practice of washing the hemodialyzer blood compartment with either bleach or hydrogen peroxide.[11]

The treatment of Type A reactions includes stopping the dialysis treatment immediately without returning the blood to the patient. The patient is then treated, depending on the severity of the symptoms, with antihistamines, steroids, bronchodilators, epinephrine, and/or vasopressors.

Type A reactions can usually be prevented by proper rinsing of the dialyzer, adequate sterilization techniques for the dialysis machine, reuse of the dialyzer, and avoiding AN-69 membranes in patients treated with an ACE inhibitor.[6] Sterilization of the dialyzer with gamma irradiation or steam and pretreatment with antihistamines and/or steroids may be necessary during the first use in patients with a previous history of a Type A reaction.

Type B reactions are more common and have milder symptoms. They have been reported more frequently (3%–5%) in patients dialyzed with less biocompatible cellulose membrane.[1],[2] They generally occur later than 30 min after the start of the session. Symptoms are very variable and may include dyspnea, chest pain, headache, nausea, vomiting, and hypotension. Type B reactions are believed to be mediated by complement,[12] the degree of which is progressively less as the biocompatibility of the membrane increases. Marked and transient neutropenia are frequently seen.

The treatment of type B reactions is typically supportive since the symptoms characteristically resolve as dialysis is continued. The syndrome can be minimized or prevented by reuse of the dialyzer, which reduces complement activation. In some cases, it may be necessary to change to a more biocompatible membrane to relieve symptoms.

Differential diagnoses of type A and type B reactions include other acute complications during hemodialysis, including, but not limited to, hemolysis, air embolism, dialysis-associated hypotension, dialysis-induced hypoxemia, and dialysis disequilibrium.


  Conclusion Top


Hypersensitivity reactions to hemodialysis membranes continue to be observed and disappear following a change of membrane, usually to cellulose triacetate. The cause of these reactions remains obscure and both the nature of the membrane and the changes in native proteins denatured after contact with dialysis-related molecules have been proposed. Clinicians should remain vigilant and be cognizant of the possibility of hypersensitivity reactions to hemodialysis membranes, as some of the reactions could be potentially life-threatening. Proper rinsing of the dialyzer, adequate sterilization techniques for the dialysis machine, reuse of the dialyzer, and avoiding AN-69 membranes in patients treated with an ACE inhibitor, has been proposed as some preventive methods.

Informed consent

Written consent was obtained from the patient to publish this case.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Daugirdas JT, Ing TS. First-use reactions during hemodialysis: A definition of subtypes. Kidney Int Suppl 1988;24:S37-43.  Back to cited text no. 1
    
2.
Esteras R, Martín-Navarro J, Ledesma G, Fernández-Prado R, Carreño G, Cintra M, et al. Incidence of hypersensitivity reactions during hemodialysis. Kidney Blood Press Res 2018;43:1472-8.  Back to cited text no. 2
    
3.
Lemke HD, Heidland A, Schaefer RM. Hypersensitivity reactions during haemodialysis: Role of complement fragments and ethylene oxide antibodies. Nephrol Dial Transplant 1990;5:264-9.  Back to cited text no. 3
    
4.
Maurice F, Rivory JP, Larsson PH, Johansson SG, Bousquet J. Anaphylactic shock caused by formaldehyde in a patient undergoing long-term hemodialysis. J Allergy Clin Immunol 1986;77:594-7.  Back to cited text no. 4
    
5.
Spartà G, Kemper MJ, Gerber AC, Goetschel P, Neuhaus TJ. Latex allergy in children with urological malformation and chronic renal failure. J Urol 2004;171:1647-9.  Back to cited text no. 5
    
6.
Brunet P, Jaber K, Berland Y, Baz M. Anaphylactoid reactions during hemodialysis and hemofiltration: Role of associating AN69 membrane and angiotensin I-converting enzyme inhibitors. Am J Kidney Dis 1992;19:444-7.  Back to cited text no. 6
    
7.
Martin-Navarro J, Esteras R, Castillo E, Carriazo S, Fernández-Prado R, Gracia-Iguacel C, et al. Reactions to synthetic membranes dialyzers: Is there an increase in incidence? Kidney Blood Press Res 2019;44:907-14.  Back to cited text no. 7
    
8.
Boer WH, Liem Y, de Beus E, Abrahams AC. Acute reactions to polysulfone/polyethersulfone dialysers: Literature review and management. Neth J Med 2017;75:4-13.  Back to cited text no. 8
    
9.
Arenas MD, Gil MT, Carretón MA, Moledous A, Albiach B. Adverse reactions to polysulphone membrane dialyzers durind hemodialysis. Nefrologia 2007;27:638-42.  Back to cited text no. 9
    
10.
Sánchez-Villanueva RJ, González E, Quirce S, Díaz R, Alvarez L, Menéndez D, et al. Hypersensitivity reactions to synthetic haemodialysis membranes. Nefrologia 2014;34:520-5.  Back to cited text no. 10
    
11.
Centers for Disease Control (CDC). Update: Acute allergic reactions associated with reprocessed hemodialyzers – United States, 1989-1990. MMWR Morb Mortal Wkly Rep 1991;40:147, 153-4.  Back to cited text no. 11
    
12.
Hakim RM, Breillatt J, Lazarus JM, Port FK. Complement activation and hypersensitivity reactions to dialysis membranes. N Engl J Med 1984;311:878-82.  Back to cited text no. 12
    


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