22 - Glomerulonephritis Associated With Complement Disorders

Abstract

Glomerular diseases associated with primary abnormalities of the complement system include thrombotic microangiopathy and C3 glomerulopathy. C3 glomerulopathy is a disease caused by a failure to control the alternative pathway of complement activation either in the circulation or in the glomerulus itself. It is characterized by deposition of C3 in the glomerulus with absent or scanty deposits of immunoglobulins. On electron microscopy there may be very dense deposits within glomerular basement membranes—dense deposit disease. Cases in which deposits do not have this characteristic appearance are known as C3 glomerulonephritis. Many patients with C3 glomerulopathy have a C3 nephritic factor—an autoantibody that stabilizes the alternative pathway C3 convertase. Rarer causes of familial disease include loss of function mutations in complement control proteins such as factor H or gain of function mutations in factor H–related genes. At presentation most patients have hematuria and proteinuria, with many having nephrotic syndrome. Currently there is no specific treatment and most patients with significant proteinuria are given immunosuppressive therapy with steroids or mycophenolate mofetil. Inhibitors of the complement alternative pathway are in clinical development and may offer more specific therapeutic options in future.