Thesis topic proposal
László Dézsi
Development and application of nanomedicinal methods in order to study hypersensitivity reactions


Institute: Semmelweis University, Budapest
theoretical medicine
Doctoral School of Basic and Translational Medicine

Thesis supervisor: László Dézsi
Location of studies (in Hungarian): Semmelweis University
Abbreviation of location of studies: SE

Description of the research topic:

Investigation of pathomechanism of acute and delayed reactions during hemodialysis, and its clinical relevance

At the beginning of the development of hemodialysis technique, acute dialysis reactions were common. The bio-incompatible cellulose membranes used at this time activated the complement system, and the ethylene oxide used for sterilization also triggered IgE-mediated allergic reactions. Ethylene oxide is no longer used for sterilization of dialysis membranes, so no reaction of this kind is seen. However, complications associated with the dialysis membrane still occur despite the use of biocompatible polysulphone/polyethersulfon dialysers. Although their frequency is negligible compared to their million-times usage, they have recently been increasing.
During extracorporeal treatments, especially hemodialysis treatment, the blood of end stage renal failure patients contacts with artificial materials. Possible dialysis reactions endanger the survival of the patient with renal failure, and therefore examination of the pathomechanism is essential, and its exploration may help to prevent such reactions. The cause of acute and life-threatening membrane reactions during dialysis is unknown. In the clinical cases reported so far, acute dialysis reactions have always occurred with the use of polysulfone (polysulfone/polyethersulfone - PSu/PESu) membranes. The onset of acute dialysis reaction occurs within 30 minutes after initiation of dialysis. The most common clinical symptoms are dispnea (69%), hypotension (66%), hypoxia (bronchospasm) (25%), chest pain (22%), skin itching (22%), abdominal symptoms (22%). The importance of the unique chemical structure of the membrane is that in patients with recent polysulfone-based but modified, biocompatible PSu/PESu dialyzers, attempts to use similar polysulfone-based membranes may be dangerous, while switching to membranes in which polysulfone is substituted (polymethylmethacrylat, polyacrylonitrile) completely prevents the reactions. Although membrane-mediated events resemble those observed in complement activation related pseudoallergy (CARPA), it still has to be proven, which may be the starting point for further research. Heparin, intravenously administered iron complex, and erythropoietin may also cause allergic reactions during dialysis treatment. On the basis of these, these reactions may have other correlations with the clinical parameters, such as the demographic and laboratory data, medication, and dialysis characteristics. Mapping these relationships can help identify high-risk patients and better understand the mechanism of membrane reactions.
In an animal study, we conducted pig hemodialysis treatments and planning to do more. In the framework of this project we plan to further analyse the results obtained during the animal testing. Blood samples from our experiments are being analysed. Based on the results obtained, we also plan to perform human measurements. For this purpose, access to data and samples of hemodilalysed patients is provided.

Number of students who can be accepted: 3

Deadline for application: 2019-12-31

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