Contributions to the study of the complement system in IgA nephropathy and dialysis

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    Abstract

    Deregulation or excessive activation of the complement system is now considered a fundamental aspect of the pathogenesis of a wide-spectrum of immune-mediated and inflammatory diseases, and it is particularly involved in kidney diseases. Chronic kidney disease (CKD) is recognized as a major health-care problem due to its increasing prevalence and association with cardiovascular mortality, costs to healthcare systems, and patient well-being.

    The current work presented in this thesis contributes to, and expands the notion of, the involvement of the complement system in various pathological processes taking part in the progression of CKD and in the uremic milieu in dialysis patients. Particularly, in a common glomerular disease such as IgA nephropathy (IgAN), it was shown that C4d, as both a glomerular and potentially vascular biomarker of lectin pathway (LP) activation, identifies a subgroup of patients with a worse prognosis in this very complex and heterogeneous disease, that may benefit from different clinical approaches. Also, in hemodialysis (HD) patients with higher levels of intra-dialytic complement activation indicated by an increased C3d/C3-ratio, a higher risk of a cardiovascular event was identified. Furthermore, in CKD and HD patients who were administered intravenous iron formulations, particularly iron sucrose, complement activation measured through sC5b-9 levels was documented, expanding the list of potential side effects of this commonly administered drug in HD patients. Finally, in peritoneal dialysis (PD), both local and systemic complement activation was demonstrated to occur through apparently different triggering pathways, and strikingly, systemic sC5b-9 levels were significantly higher than those found in HD patients.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Berger, Stefan, Supervisor
    • Pestana, Manuel, Supervisor, External person
    • Seelen, Marcus, Co-supervisor
    • Poppelaars, Felix, Co-supervisor
    Award date20-Jan-2021
    Place of Publication[Groningen]
    Publisher
    DOIs
    Publication statusPublished - 2021

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