Immunosuppressive Treatment in C3 Glomerulopathy: Time to Reconsider Our Approach

complement complex is entirely different compared to MPGN with immunoglobulin deposits [2] . The pathogenesis of C3 deposition in the glomeruli of immunoglobulin-negative MPGN is, however, very heterogenous and includes, in a minority of patients (<20%), various genetic causes, for example, mutations of CFH, CFI, and in CFHR5 nephropathy, most frequently internal duplication of CFHR5 gene. Additionally, the C3 glomerulopathy may be caused by the not routinely detected autoantibodies directed at complement factor B, CFH, and autoantibodies stabilizing C3 convertase – C3bBb, previously called “nephritic factor” (C3 NeF) [3] . Unfortunately, in clinical practice, etiology remains unknown in most patients. The outcome of patients with C3 glomerulonephritis is poor with >50% having substantial renal dysfunction within 12 years [4] . However, the outcome was initially predicted to be better than that of DDD, as >50% of patients with DDD progress to end-stage renal disease (ESRD) within 10 years [5] . In a recent paper [6], patients with DDD were compared to those with C3 glomerulonephritis, those who were younger and to those who tended to have lower serum C3 levels and greater probability of crescentic GN. Conversely, patients with C3 glomerulonephritis were older and had more severe arterioCaliskan et al. [1] in their retrospective analysis compared the outcomes of 66 patients with C3 glomerulopathy who were treated with mycophenolate mofetil, with cyclophosphamide-based treatment, or by adopting conservative treatment methods. The primary outcome (chronic kidney disease stage 5 or decrease of estimated glomerular filtration rate [eGFR] by more than 50%) was not significantly different between the groups with 25.8% of patients achieving the primary outcome within the median follow-up of 28 months. Numerically the percentage of patients achieving the primary outcome was similar among mycophenolate-treated patients and patients on conservative treatment (29.6 vs. 31.3%, respectively). Clinical predictors of poor outcome were young age, higher proteinuria, and lower eGFR at presentation. With regard to the histology, poor outcome was related to the percentage of crescentic and sclerotic glomeruli and to the severity of interstitial fibrosis. C3 glomerulopathy, a newly defined subgroup of membranoproliferative immunoglobuline-negative glomerulonephritis (MPGN), includes dense deposit disease (DDD, formerly MPGN type 2) and immunoglobulinnegative type I and type III MPGN (C3 glomerulonephritis). Its pathogenesis is characterized by the dysregulation of the alternative complement pathway, and the terminal Published online: July 13, 2017 Nephrology American Journal of