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Published on: May 4, 2017
Complement inhibitors for kidney disease
Benjamin Wooden1, Blanca Tarragon1, Mariela Navarro-Torres1
1Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, NY, USA.
Insights
Novel therapies targeting the complement system offer new hope for kidney diseases. Research shows complement inhibition, from C5 to C3, can modify disease progression in conditions like C3 glomerulopathy and IgA nephropathy.
Area of Science:
- Nephrology
- Immunology
- Pharmacology
Background:
- The complement system, crucial in immune responses, significantly contributes to kidney disease pathogenesis.
- Understanding complement activation via classical, lectin, and alternative pathways is key to developing targeted therapies.
- Diseases like C3 glomerulopathy and immunoglobulin A nephropathy involve complement dysregulation.
Conclusions:
- Complement inhibition represents a promising therapeutic avenue for kidney diseases.
- Targeting upstream complement components like C3 offers potential for broader therapeutic impact.
- The field is progressing towards more precise and effective complement-modulating treatments for renal pathologies.
Abstract:
A refined understanding of the role of complement in the pathogenesis of glomerular and other kidney diseases has, over the past two decades, been matched by the development of novel, complement-targeting therapies. As we increasingly recognize the important role that complement activation across all three pathways-classical, lectin and alternative-plays in glomerular lesions both rare (e.g. C3 glomerulopathy) and common (e.g. immunoglobulin A nephropathy), we can identify avenues for precise, targeted approaches to modifying the natural history of these kidney diseases. In this review, we survey the evidence on using complement inhibition from the earliest, small-scale studies focusing on C5-targeting agents to more recent, large, multicenter, randomized trials utilizing complement blockade higher up in the complement pathway at the level of C3. We conclude by examining where the field of complement targeting therapy may be headed in light of these studies.
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