Internal medicine

Pathology

Eculizumab

Disease

Glomerulopathy

Complement system

Alternative complement pathway

Antibody

Immunology

Biopsy

Proteinuria

Atypical hemolytic uremic syndrome

Kidney

Renal biopsy

Complement component 5

Transplantation

End stage renal disease

Medicine

American Journal of Medical Genetics Part C Seminars in Medical Genetics

C3 glomerulopathy (C3G) describes a pathologic pattern of injury diagnosed by renal biopsy. It is characterized by the dominant deposition of the third component of complement (C3) in the renal glomerulus as resolved by immunofluorescence microscopy. The underlying pathophysiology is driven by dysregulation of the alternative pathway of complement in the fluid‐phase and in the glomerular microenvironment. Characterization of clinical features and a targeted evaluation for indices and drivers of complement dysregulation are necessary for optimal patient care. Autoantibodies to the C3 and C5 convertases of complement are the most commonly detected drivers of complement dysregulation, although genetic mutations in complement genes can also be found. Approximately half of patients progress to end‐stage renal disease within 10 years of diagnosis, and, while transplantation is a viable option, there is high risk for disease recurrence and allograft failure. This poor outcome reflects the lack of disease‐specific therapy for C3G, relegating patients to symptomatic treatment to minimize proteinuria and suppress renal inflammation. Fortunately, the future is bright as several anti‐complement drugs are currently in clinical trials.

<scp>C3</scp> glomerulopathy: Understanding an ultra‐rare complement‐mediated renal disease

C3 glomerulopathy: Understanding an ultra‐rare complement‐mediated renal disease