Comparison of Histopathologic Findings with Patterns of Immunofluorescence Staining in Native Kidney Biopsies Diagnostic for IgA Nephropathy

Background: Although IgA nephropathy (IgAN) is the most common type of primary glomerulonephritis worldwide, there is still much to be understood about the relationship of glomerular complement deposition to disease activity and prognosis. Prior studies suggest the degree of C3 deposition may represent an important pathogenetic and clinical prognostic factor. Our study aims to investigate the relationship between morphologic pathologic features observed by light microscopy (and documented using the Oxford scoring system) with results of immunofluorescent staining techniques for examining IgA and C3 deposition. Methods: A total of 57 cases (n = 57) of IgAN, each representing a unique patient, and diagnosed by 3 different renal pathologists, are included in this study. Case data are collected retrospectively, and correlation matrix analysis is used to examine the relationship between intensity of C3 and IgA staining and the rendered Oxford scores for each biopsy. Results: Cases with C3 staining show higher total scores by the Oxford scoring system [r= 0.22, CI: 90%; p = 0.05]. Significant positive correlations between the intensity of C3 and IgA staining [r= 0.59, CI: 90%; p = <0.001], and between C3 staining intensity and mesangial cellularity score (M) [r= 0.19, CI: 90%; p = 0.06] are found. Although not reaching the level of statistical significance, a positive correlation is demonstrated between C3 staining intensity and endocapillary hypercellularity (E), interstitial fibrosis/tubular atrophy (T), and crescent (C) scores, but C3 staining intensity, and segmental sclerosis (S) score show a negative correlation. Interestingly, correlation analyses resulted in quite disparate findings when comparing series of cases diagnosed by separate pathologists, suggesting there may be a high degree of interobserver variability in assessment of these pathologic findings. Conclusion: C3 deposition may play an important role in IgAN pathogenesis, and with the advent of complement inhibiting drugs, updates to the diagnostic approach and clinical management of IgAN are necessary. Further higher-powered studies examining the molecular, clinical, and histopathologic relationships of complement activity in IgAN should help elucidate the utility of these novel complement-inhibiting therapies in the management of IgAN.