Novel aspects of complement in kidney injury

Complement activation is integral to the development and progression of multiple forms of kidney disease. The liver is the principal source of serum complement, but various kidney cell types and bone marrow–derived immune cells can produce a full array of complement proteins. Locally produced and activated complement yields cleavage products that function as vital intermediaries, amplifying inflammation in ischemia–reperfusion injury and transplant rejection, among other pathological states. Additional new studies indicate that during cognate T-cell–antigen presenting cell interactions, both cell types produce alternative pathway complement components. The resultant activation products have an essential role in T-cell activation, expansion, and differentiation, which in turn has a profound impact on the development of immune-mediated kidney disease. The recognition of an expanded role for kidney cell–derived and immune cell–produced complement as pathogenic to the kidney supports the need for future studies to test the efficacy of complement inhibitors in the prevention and/or treatment of selected kidney diseases.