Topic Discussion: Complement and the Kidney

The complement system can be attacked to help treat kidney disease. Complement activation contributes to the pathogenesis of acute and chronic kidney disease injury.  The aHUS and C3GN story has led us to believe that there might be hope for other potential targets in the complement system for patients with kidney disease.

A recent mini review in KI summarizes the role of the complement system in kidney disease and where future drugs hold promise. The complement activation is initiated via 3 pathways- classical, alternative and lectin.  Full activation leads to the generation of several biologically active fragments, namely C3a, C5a, C3b and C5b-9.  Drugs are currently being developed to block the classical pathway, the alternative pathway and the activation at the level of c3,c5 and c5a.

C1 inhibitors, TNT009( anti C1s) affect the classical pathway
Purified factor H, anti Factor D agents, CR2-factor H, affect the alternative pathway
Compstatin and soluble CR1 inhibits at level of C3
Eculizumab and other anti C5 inhibit at level of C5
and CCX168 inhibits at level of C5a

Check out two excellent reviews, one in KI and other in KIR
http://www.kidney-international.org/article/S0085-2538(16)30185-5/fulltext
http://www.kireports.org/article/S2468-0249(16)30031-6/fulltext