Kidney diseases caused by complement dysregulation: acquired, inherited, and still more to come

Area of Science:

• Nephrology
• Immunology
• Genetics

Background:

• The complement alternative pathway is implicated in various renal diseases.
• Genetic variants in complement regulatory proteins are increasingly identified as causes of complement-associated glomerulopathies.
• Defective complement control leads to activated complement product deposition in the glomeruli.

Purpose of the Study:

• To summarize the role of complement alternative pathway dysregulation in renal diseases.
• To highlight the significance of genetic factors in C3 glomerulopathies.
• To discuss current and future therapeutic strategies for complement-related glomerulopathies.

Main Methods:

• Review of recent literature on complement alternative pathway genetics and glomerulopathies.
• Analysis of the role of complement component 3 (C3) deposition in disease classification.
• Evaluation of therapeutic approaches including complement blockade and plasma substitution.

Main Results:

• C3 glomerulopathies are defined by glomerular C3 deposition without immunoglobulin deposits.
• Identification of mutations in complement regulatory proteins advances understanding of pathogenesis.
• Therapies like eculizumab and plasma substitution show promise in managing C3 glomerulopathies.

Conclusions:

• Complement alternative pathway dysregulation is central to C3 glomerulopathies.
• Further research into underlying defects is needed for precise, pathogenesis-specific therapies.
• Targeting complement regulation offers therapeutic potential for these renal diseases.