Involvement of complement components in renal disease.

The complement system is a critical element of innate immunity whose role in renal physiology and disease is illustrated by the following observations: (1) a deficiency or inhibition of a complement regulatory protein results in renal tissue damage; (2) inhibition of complement activation (with cobra venom factor or sCR1), or in C6-deficient rats, attenuates complement-mediated tissue destruction; and (3) ongoing glomerular disease has been associated with the deposition/expression of complement proteins in glomerular or tubular structures and the excretion of C5b-9 and CD59 proteins. Complement activation by cellulosic membranes results in the production of C5a, which has now been shown to provoke most of the same inflammatory responses observed during hemodialysis. Controlling the dose of C5a given during dialysis, by controlling blood flow rates or membrane types, may have an impact on patient health. Finally, lessons learned in the xenotransplant setting suggest that complement activation can be effectively controlled to limit inflammation (with sCR1 or anti-C5 monoclonal antibodies). Recent developments in this area may lead to new therapeutic approaches to deal with the complex etiology of renal disease.