The impact of reclassification of C3 predominant glomerulopathies on diagnostic accuracy, outcome and prognosis in patients with C3 glomerulonephritis

Abstract

Background: C3 glomerulonephritis is a recently described entity with heterogeneous histopathological features. This study was conducted to assess the effect of reclassification of C3 glomerulopathies on renal outcomes, mortality, and response to therapy. Methods: We undertook a retrospective analysis of 857 renal biopsies collected at The Canberra Hospital. Samples with predominant C3 staining were reviewed by a renal histopathologist. Of 31 biopsies with predominant C3 staining, 10 fulfilled histological criteria for C3 glomerulonephritis, while the remaining 21 cases were used as C3 Controls. Results: Aside from a higher incidence of C3 glomerulonephritis in Torres Strait islanders (40% vs 5% C3 Controls, p = 0.04), presentation demographics were similar between the two groups. Median creatinine at diagnosis was higher in patients with C3 glomerulonephritis (253 umol/L IQR 103–333 vs 127 umol/L C3 Controls, IQR 105–182, p = 0.01). Prior to reclassification, a majority of C3 glomerulonephritis cases were diagnosed as membranoproliferative glomerulonephritis (60% vs 5% (C3 Controls) p < 0.01). Electron microscopy demonstrated all C3 glomerulonephritis patients had C3 deposition (100% vs 38% p = 0.02), these deposits were amorphous in nature (50% vs 5% respectively p = 0.007). C3 glomerulonephritis patients had shorter median follow-up (405 days IQR 203–1197 vs 1822 days respectively, IQR 1243–3948, p = 0.02). Mortality was higher in C3 glomerulonephritis patients (30% vs 14% in C3 Controls (log rank p = 0.02)). Conclusion: We have devised a diagnostic and treatment algorithm based on the results of literature review and our current study. Further prospective assessment is required to review diagnostic and treatment outcomes for this disease in Australian centres