Successful therapy of C3Nef-positive C3 glomerulopathy with plasma therapy and immunosuppression.

BACKGROUND: C3 glomerulopathies (C3G) are characterized by uncontrolled activation of the alternative pathway of complement. In most patients these diseases progress towards end-stage renal disease, and the risk of recurrence after renal transplantation is high. In the majority of patients, only antibodies against the C3 convertase, termed C3Nef, can be found as a potential pathogenic factor. Although a large variety of therapeutic approaches have been used, no generally accepted therapy exists.
METHODS: In four consecutive patients with C3G in whom all known complement factor mutations were excluded and only C3Nef could be identified as a potential cause of disease, a multimodal therapeutic regimen with plasma therapy, corticosteroids and mycophenolate mofetil was used.
RESULTS: The multimodal regimen achieved normalization of renal function in all four patients, with complete remission in two patients and a distinct reduction of proteinuria in the other two patients. The single patient with C3 glomerulonephritis (C3GN) and marked terminal complement complex elevation only showed partial remission; further improvement was achieved following the addition of eculizumab to the therapeutic regimen. Repeatedly measured C3Nef levels did not correlate with disease course or therapeutic response in any of the patients.
CONCLUSIONS: As this multimodal therapeutic approach was effective in all four treated patients with suspected autoimmune etiology of C3G, it offers a treatment option for severely affected patients with this rare disease until more specific regimens are available.