IgM and C3 Deposition in Primary Focal Segmental Glomerulosclerosis (FSGS): A Clinical and Histopathological Spectrum

Focal segmental glomerulosclerosis (FSGS) is a common renal disorder, characterized by progressive segmental sclerosis of renal glomeruli and clinical symptoms corresponding to proteinuria. Classically, it is not considered to be an antibody-mediated disease, however, IgM and C3 deposition may be seen in a subset of cases of FSGS. The impact of this immune deposition on histopathological features in renal core biopsies, on the urinary biochemical parameters, and the clinical outcomes, has not been previously investigated in our population. The aim of this study is to analyze the aforementioned parameters in patients with primary FSGS having antibody deposition as compared to those who do not have any antibody deposition. Some 155 patients diagnosed with FSGS were retrospectively enrolled in our study. The renal biopsies were reviewed for histopathological features and immunofluorescence (IF) findings of IgM and C3 glomerular deposition. These histological features were then compared with the biochemical parameters as well as the clinical outcomes of patients. The patients were assigned to Groups 1 and 2 based on the IF findings. The IgM and/or C3 glomerular deposition had a low incidence in patients with primary FSGS in our study (28.3%). Patients having IgM and C3 co-deposition had a significantly longer time duration since the onset of their clinical symptoms; active disease duration (42 months vs 22 months, p=0.049). The mean pre-treatment serum creatinine of patients with IgM and C3 co-deposition was 6.00 mg/dL as compared to 3.29 mg/dL in patients with no immune deposition (p=0.037). The immune deposition was associated with higher rates of segmental and global glomerulosclerosis, but this finding along with other evaluated histological parameters did not show statistical significance. The number of patients having IgM and/or C3 deposition and with active steroid use/renal dialysis was similar to patients having no IgM and/or C3 deposition. The IgM and/or C3 deposition in FSGS has a low incidence within and is not associated with any significant differences in histological parameters on renal core biopsies of patients from the Pakistani population. IgM and/or C3 deposition is also associated with a significantly longer duration of active disease and these patients may present with higher pre-treatment serum creatinine. Other biochemical parameters and clinical outcomes appear comparable between the groups based on the available clinical data.