GDNF and focal segmental glomerulosclerosis: In FSGS patients with progressive proteinuria, protein-overload mice and in vitro podocyte culture, C3a/C3aR caused podocyte damage by activating glial cell line-derived neurotrophic factor (GDNF)/c-Ret (the receptor of GDNF) pathway, which is a critical adaptive response when podocytes are exposed to toxic injury.