Distinctions between C1q Nephropathy and Other Glomerular Diseases with Overlapping Clinical and Pathologic Features

Background: C1q nephropathy (C1qN) has prominent mesangial C1q immunostaining with varying staining for immunoglobulins. C1qN has overlapping clinical and pathologic features with minimal change disease (MCD), IgM nephropathy (IgMN), focal segmental glomerulosclerosis (FSGS), and class I/II (mesangiopathic) lupus nephritis (MLN). The distinctiveness of C1qN is controversial. C1qN is often considered a variant of MCD and FSGS, or seronegative LN. We compared C1qN demographic, clinical and pathologic features to IgMN, MLN, FSGS and MCD. Methods: Using data from the UNC Glomerular Disease Collaborative Network, demographic, clinical, and kidney biopsy light microscopy (LM), immunofluorescence (IF) and electron microscopy (EM) data were analyzed from 150 C1qN, 34 IgMN, 104 MLN, 279 FSGS and 115 MCD patients. Diagnosis of C1q nephropathy required C1q staining ≥2+ (scale of 0-4+) with no clinical SLE. Pathology data was prospectively scored at diagnosis. Statistically significant distinctions between C1qN and other glomerular diseases were identified. Results: As shown in the Table, IF and other pathologic features of C1qN, IgMN, FSGS and MCD are different. Compared to C1qN, these patterns of injury have different LM, EM, demographic and clinical features supporting the possibility of different etiologies and pathogenic mechanisms. C1qN has overlapping IF features with MLN and IgMN but demographic and serologic parameters are different. C1qN has pathologic features overlapping with FSGS and MCD but demographic profile is different. Conclusion: Compared to IgMN, MLN, FSGS and MCD, C1q nephropathy has different pathologic, demographic and clinical features suggesting different etiology and pathogenesis, and different outcome and response to treatment. The next step with these cohorts is analysis of clinical outcomes and responses to therapy.