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Is complement a target for therapy in renal disease?
1Academic Renal Unit, University of Bristol, Bristol, England, United Kingdom. p.mathieson@bris.ac.uk
Insights
The complement system directly causes kidney injury, particularly in glomerulonephritis. New therapies targeting this pathway offer hope for treating renal diseases and preventing transplant rejection.
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Complement deposition is common in injured kidneys, especially with glomerulonephritis.
- The complement system's role in kidney tissue injury is increasingly understood.
- Local complement production occurs within the kidney.
Purpose of the Study:
- To review the complement pathway, its regulation, and mechanisms of complement-induced kidney injury.
- To discuss the renal consequences of complement dysregulation.
- To examine current and future therapeutic strategies targeting the complement system.
Main Methods:
- Narrative review of existing literature.
- Overview of complement pathway and regulatory mechanisms.
- Analysis of complement's role in renal disease and xenotransplantation.
Main Results:
- Complement activation can directly cause kidney tissue injury.
- The complement system plays a causal role in specific renal diseases.
- Therapies targeting complement activation are emerging.
Conclusions:
- The complement system is a direct cause of injury in certain kidney diseases.
- Specific therapies can interrupt complement activation or promote regulation.
- Complement inhibitors developed for xenotransplantation hold promise for primary renal diseases.
Abstract:
Complement deposition in the injured kidney is common, especially in glomerulonephritis. The precise role of the complement system in the mediation of tissue injury in the kidney has been defined in recent years, and this has assumed extra importance with the recent development of specific forms of therapy directed at the complement pathway. As well as the induction of cell lysis, complement has many subtle effects on cell biology, particularly on endothelial cells. Complement components are produced locally in the kidney. Detailed studies of certain rare forms of nephritis have provided evidence that complement activation can directly cause tissue injury. Appreciation of the importance of complement in hyperacute rejection of xenotransplants has given new impetus to the development of complement inhibitors. A narrative review is provided, with a brief overview of the complement pathway and its regulatory mechanisms, mechanisms of complement-induced tissue injury, local complement production, and the renal consequences of complement dysregulation. Currently available forms of therapy aimed at the complement system are reviewed, and possible future therapeutic strategies are suggested. The complement system plays a direct causal role in tissue injury in certain forms of renal disease. Specific forms of therapy are becoming available that can selectively interrupt complement activation or promote its regulation. Much of the drive for the development of these therapies comes from the field of xenotransplantation, but these forms of therapy should also be tested in various primary renal diseases.