NEPHRITIC FACTORS PREDISPOSE TO CHRONIC GLOMERULONEPHRITIS

Chronic glomerulonephritis has been reported in three rare conditions in which factor H of the complement system does not function normally. Factor H is essential for the inactivation of the C3b-dependent conve rtase, C3b,Bb, which is constantly being formed in vivo. With factor H dysfunction, this convertase accumulates and produces hypocomplemente mia. Twenty-two individuals have been reported with the three forms of H dysfunction, and 12 have displayed evidence of chronic glomerulonep hritis. In addition, matings of certain Yorkshire pigs result in offsp ring that are homozygous deficient in factor H and have a high inciden ce of a severe hypocomplementemic glomerulonephritis closely resemblin g membranoproliferative glomerulonephritis type II. The hypothesis pro posed is that the nephritis that develops with these forms of H dysfun ction is in some way the result of circulating convertase. The corolla ry is that nephritic factors, also producing H dysfunction and higher than normal circulating levels of the C3b-dependent convertase, are re sponsible for the glomerulonephritides with which they are associated, mainly membranoproliferative glomerulonephritis types II and III. Nep hritic factors are autoantibodies that bind to the C3b-dependent conve rtase and render it resistant to dissociation by factor H. Although ne phritic factors are currently considered epiphenomena, their role in t he pathogenesis of membranoproliferative glomerulonephritis should be reconsidered based on the evidence that circulating convertase is neph ritogenic. (C) 1994 by the National Kidney Foundation, Inc.