Due date for 2022 – December 30, 2021
Earliest start date – April 1, 2022
Available data on C3G support the following:
C3G is a rare complement-mediated renal disease. DDD and C3GN are subtypes of C3G. 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. Triggers that result in alternative pathway dysfunction include genetic mutations in complement genes 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 in the serum. This test should be ordered if you are considering Eculizumab.
For relevant articles please see:
Lu DF, Moon M, Lanning LD, McCarthy AM, Smith RJH. Clinical features and outcomes of 98 children and adults with Dense Deposit Disease. Pediatr Nephrol 2011 Nov 22 [Epub ahead of print]; 27(5):773-81, 2012.
Smith RJH, Harris CL, Pickering MC. Dense deposit disease. Mole Immunol 2011 May 21 [Epub ahead of print]; 48(14):1604-10, 2011. PMID: 21601923.
Zhang Y, Meyer NC, Wang K, Nishimura C, Frees K, Jones M, Katz LM, Sethi S, Smith RJH. Causes of alternative pathway dysregulation in Dense Deposit Disease. Clin J Am Soc Nephrol 2012 Jan 5 [Epub ahead of print]; 7:265-74, 2012.
Bomback AS, Smith RJH, Barile GR, Zhang Y, Heher EC, Herlitz L, Stokes MB, Markowitz GS, D'Agati VD, Canetta PA, Radhakrishnan J, Appel GB. Eculizumab for Dense Deposit Disease and C3 Glomerulonephritis. Clin J Am Soc Nephrol 2012 Mar 8 [Epub ahead of print]; 7(5):748-56, 2012.