Inherited and acquired dysregulation of the complement alternative pathway plays an important role in multiple renal diseases. In recent years, the identification of disease-causing mutations and genetic variants in complement regulatory proteins has contributed significantly to our knowledge of the pathogenesis of complement associated glomerulopathies. In these diseases defective complement control leading to the deposition of activated complement products plays a key role. Consequently, complement-related glomerulopathies characterized by glomerular complement component 3 (C3) deposition in the absence of local immunoglobulin deposits are now collectively described by the term “C3 glomerulopathies.” Therapeutic strategies for reestablishing complement regulation by either complement blockade with the anti-C5 monoclonal antibody eculizumab or plasma substitution have been successful in several cases of C3 glomerulopathies. However, further elucidation of the underlying defects in the alternative complement pathway is awaited to develop pathogenesis-specific therapies. 1. Introduction The central function of the kidney for whole body homeostasis is based on adequate blood flow and pressure, sufficient glomerular capillary surface for selective filtration, and subsequent secretion and reabsorption of solutes in the tubular system. The essential role of the glomerulus as a filtration unit can be estimated by the fact that most diseases leading to chronic kidney disease and end-stage renal disease with the need for dialysis or transplantation are caused by glomerulopathies. The glomerulus as a specialized capillary convolute is prone to any vascular damage and is affected as part of a generalized microangiopathy in common diseases such as diabetes mellitus or arterial hypertension. However, the glomerulus can also be affected by specific circulating factors, including antibodies against glomerular antigens, circulating immune complexes, or activated factors of a dysregulated complement system. The complement system as an essential component of the innate immune system plays an indispensable role in the elimination of invading microorganisms as a first line of defense [1, 2]. Furthermore, the complement system bridges innate and adaptive immunity. The cross-talk between toll-like receptors—as another key component of the innate immune system—and the complement system has been a key aspect of research as of their synergistic interaction to increase activation of inflammatory responses [3]. Complement activation runs through three major pathways (classic,
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