How C3 Glomerulopathy Progresses

1. Initiation:

- Genetic predisposition (APOL1 risk variants)

- Environmental triggers (infections, toxins)

2. Complement activation:

- Dysregulation of the alternative complement pathway

- Deposition of C3 fragments on the glomerular basement membrane (GBM)

3. Leukocyte infiltration:

- Neutrophils and macrophages are recruited to the affected glomeruli

- Release of inflammatory mediators and proteases

4. Glomerular inflammation:

- Mesangial expansion and proliferation

- Thickening of the GBM

- Endothelial cell activation

5. Podocyte injury:

- Podocytes are damaged by inflammation and complement activation

- Loss of podocytes leads to proteinuria and glomerulosclerosis

6. Progression to chronic kidney disease (CKD):

- Persistent inflammation and injury lead to progressive loss of kidney function

- Development of end-stage renal disease (ESRD) may require dialysis or kidney transplantation