Complement-Mediated Glomerular Diseases

The complement system plays a major role in microbial killing, but it has other key functions, such as regulation of inflammatory reactions and development of proficient antibody-mediated response. While in normal situation the complement system serves as a part of the host defense mechanism, its prolonged or inappropriate activation may lead to the undesirable cellular injury; therefore, there are a number of regulators of the complement cascade that protect the host from untoward tissue damage. This article describes several disease processes that result from either acquired or genetic dysregulation of the complement pathway, including membranoproliferative glomerulonephritis (MPGN), dense deposit disease, C3 glomerulonephritis, C1q nephropathy, and atypical hemolytic uremic syndrome, and discusses a recently proposed classification that separates MPGN cases into two groups: immunoglobulin and non-immunoglobulin-mediated diseases. The improved understanding of the role of complement in MPGN led to a paradigm shift in the classification of this disease and to the emergence of a new group of diseases called the C3 glomerulopathies.