Complement and Kidney Disease (2006 edition.)

The understanding how complement relates to glomerular diseaseshas evolved considerably during the last years. Substantialevidence has accumulated that explain how a defective orderegulated complement system results in kidney diseases. Thecombination and close interaction of basic research with clinicalmedicine has demonstrated an important role of complement effectorand regulatory proteins in pathological settings of the kidney.
A large panel of distinct human kidney diseases such as hemolyticuremic syndrome (HUS), membrano proliferative glomerulonephritis(MPGN), systemic lupus erythematosus (SLE) and in ischemicreperfusions injury and transplantation are caused by defectivecomplement control. Genetic analyses have identified mutations incomplement regulators that are associated with these diseases.Mutations have been identified in the fluid phase alternativepathway regulator Factor H and the membrane regulator MembraneCofactor Protein MCP (CD46). The functional characterization of themutant proteins allows to define the pathophysiological events on amolecular level. These new concepts and data on disease mechanismsalready allowed to establish new diagnostic and novel promisingtherapeutic approaches for several human kidney diseases.