C3G is a rare complement-mediated renal disease. This term includes both DDD and C3GN. Within 10 years of diagnosis, ESRD develops in about 50% of patients.
The diagnosis of C3G requires renal biopsy. Both DDD and C3GN show C3 dominance by immunofluorescence microscopy. Electron microscopy is required to differentiate DDD and C3GN. Features of partial lipodystrophy can accompany DDD and ocular drusen can occur with both DDD and C3GN. Drusen may lead to decreased visual acuity in approximately 10% of affected patients.
The pathophysiologic basis for C3G is uncontrolled systemic activation of the alternative pathway of the complement cascade. There are different triggers that result in alternative pathway dysfunction including genetic mutations and auto-antibodies.
C3Nefs are NOT identical. The triggers that lead to the development of autoantibodies like C3Nefs are not known. There are multiple assays to test for C3Nefs. Different assays have different sensitivities.
Most treatments are ineffective at curing C3G. Symptomatic treatment for proteinuria with ACEs and ARBs is recommended. About 30% of C3GN patients will respond to MMF.
C3G and Eculizumab. About 30% of patients with C3G may respond to Eculizumab. Response can be predicted by assaying levels of soluble C5b-9 (sMAC) in the serum. This test should be ordered if you are considering Eculizumab.