Abstract
BackgroundC3 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.MethodsWe 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.ResultsAside 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)).ConclusionWe 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.
Highlights
C3 glomerulonephritis is a recently described entity with heterogeneous histopathological features
Ten of 31 biopsies examined were consistent with C3 glomerulonephritis (C3GN), whilst the remaining 21 samples were consistent with C3 mediated disease but not consistent with C3GN (Figs. 1 and 2)
C3GN cases were originally reported as Membranoproliferative glomerulonephritis (MPGN) in most patients compared to C3 Controls (60% vs 5%, p < 0.01)
Summary
C3 glomerulonephritis is a recently described entity with heterogeneous histopathological features. MPGN has been typically defined by the histopathological lesions of mesangial hypercellularity, endocapillary proliferation, and duplication of the basement membrane [1,2,3]. Advances in the understanding of immunoglobulin and complement-mediated glomerular disease have led to the proposed reclassification of MPGN, utilising histological findings in addition to evidence of the underlying pathophysiological processes [1, 3]. These include: immune complex-mediated disease (IC), complement dysregulation and overactivation, or neither complement nor IC-mediated endothelial injury [2, 4]. MPGN arising in the absence of IC or complement deposition occurs in the context of thrombotic microangiopathy, seen in haemolytic uremic syndrome and malignant hypertension [4]
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