Complement inhibition in renal diseases

The activation of complement and its deleterious consequences have been observed in many renal diseases. Complement contributes to injury in several forms of glomerulonephritis (GN), in acute and chronic humoral rejection after renal transplantation, and at the time of ischaemiaureperfusion injury. It is also thought to accelerate the progression of chronic renal damage. Most of the evidence for the role of complement in enhancing injury comes from experimental data obtained in murine models, in which the addition of complement inhibitors blocks or reduces damage. The first evidence that excessive complement activation can be reversed in humans has been recently reported by Remuzzi et al. [1]. These authors reported a combined liver and kidney transplantation in a young child with haemolytic uraemic syndrome (HUS) and a mutation of factor H by which they were able to restore the defective factor H activity with no recurrence of the disease. The biological markers of complement activation normalized after transplantation as well. In contrast to inhibitors of the coagulation cascade, the clinical application of complement inhibitors has not yet started; this might explain why so little attention has been given by clinicians to this field. With major progresses made in the last 10 years on the engineering of molecules, it is likely that complement inhibition will be introduced in clinical practice soon. Here we would like to emphasize some of the aspects of complement relevant to renal diseases, for which specific inhibitors of complement might produce beneficial effects, but also the possible caveats related to the inhibition of an enzymatic cascade central to the normal function of the innate immune system. Complement