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[Role of Complement in Kidney Diseases - New Aspects]
Peter F Zipfel1,2, Svante Zipfel3, Thorsten Wiech4
1Abteilung Infektionsbiologie, Leibniz institut für Naturstoff Forschung und Infektionsbiologie, Jena, Deutschland.
Insights
The complement system is crucial for immunity and its dysregulation causes kidney disease. New therapies targeting complement are emerging for treating various kidney disorders, including those linked to COVID-19.
Area of Science:
- Immunology
- Nephrology
- Proteolytic cascades
Context:
- The complement system, a key immune component, is intricately linked with coagulation.
- Dysfunctional complement activation and regulation contribute to severe kidney diseases.
- Recent COVID-19 infections highlight complement's role in thrombotic inflammation and kidney damage.
Purpose:
- To review recent advancements in understanding complement's role in kidney diseases.
- To discuss novel complement inhibitors and targeted therapies.
- To focus on specific complement-mediated kidney pathologies and emerging treatments.
Summary:
- This review covers the latest developments in complement's involvement in kidney diseases, including atypical hemolytic uremic syndrome, C3 glomerulopathy, ANCA-associated vasculitis, IgA nephropathy, membranous nephropathy, lupus nephritis, transplant rejection, and COVID-19-associated nephropathy.
- It highlights the growing number of approved and investigational complement inhibitors and therapies.
- The manuscript also touches upon the development of diagnostic guidelines and biomarkers for complement-mediated diseases.
Impact:
- Advances in complement inhibition offer new treatment avenues for severe kidney diseases.
- Emerging therapies show promise for conditions previously lacking effective treatments.
- The development of clinical guidelines and biomarkers will improve diagnosis and management of complement-mediated renal pathologies.
Abstract:
Complement is a central part of the immune system. In the human body, complement is responsible for recognition of infectious microbes, for coordinating the adaptive immune response, controlling homeotic reactions and for the non-inflammatory removal of modified self-cells and infectious microbes. Complement is also closely linked to another proteolytic cascade, the coagulation system. Defective activation and altered complement regulation drives pathology of several severe human kidney diseases.This manuscript summarizes the latest developments on the role of complement in kidney diseases, on new complement inhibitors and on recent complement targeting therapies. In particular focusing on diseases (1) atypical Hemolytic Uremic Syndrome, (2) C3 Glomerulopathy, (3) Anti Neutrophil Cytoplasmic Antibody Mediated Vasculitis, (4) IgA Nephropathy, (5) Membranous Glomerulopathy, (6) Systemic Lupus Erythematosus, (7) Transplant rejection and (8) COVID 19 Infection-Triggered Kidney Diseases. More excitement is generated in this field, as more and more complement mediated diseases can be treated. Several complement targeting compounds are approved by the EMA and FDA and an increasing number of new candidates are in late phase clinical trials. In addition, clinical guidelines are developed for Diagnosis and Therapy of complement mediated diseases, new biomarkers are evaluated in clinical studies, and diagnostic guidelines are in development. The recent Covid infections showed a clear link of complement in thrombo inflammation, which ultimately results in kidney damage. These aspects have increased further the focus of complement inhibitors in COVID infections.
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