Abstract
BackgroundC3 glomerulonephritis is a rare glomerulopathy characterized at renal biopsy by C3 deposition, alone or with scanty immunoglobulins, as well as by an electron-dense material in mesangium, subendothelial and subepithelial space. An abnormal systemic activation of the alternative pathway of the complement cascade is responsible for the development of the disease if triggered by several possible environmental conditions. We report the first case in literature of a patient affected by cystic fibrosis and C3GN.Case presentationOur case involves a young woman with cystic fibrosis, who had persistent microscopic hematuria, proteinuria and hypocomplementemia C3 for over three months. Renal biopsy confirmed the diagnosis of C3 glomerulopathy. Complement system dysregulation was tested and resulted in a strong terminal pathway activation proved by high levels of sC5b-9 complex, amounting to 1588 ng/ml (normal value < 400 ng/ml). Next generation sequencing (NGS) showed polymorphism in CFH (p.V62I in SCR1) and THBD (p.A473V), already known as pathogenic for C3GN, as well as a mutation in C3 (p.R102G) associated only with age-related macular degeneration (AMD) so far. Treatment was based on ACE inhibitors and kidney function is currently stable (GFR 50 ml/min, serum creatinine 1.7).ConclusionsThe co-existence of C3 glomerulopathy in a patient with CF, which is characterized by chronic infection/inflammation, makes this case an interesting model of chronic altered systemic activation of the alternative pathway of the complement cascade.
Highlights
BackgroundC3 glomerulonephritis (C3GN) has been recently included with Dense Deposit Disease (DDD) in the new entity of C3 glomerulopathy
C3 glomerulonephritis is a rare glomerulopathy characterized at renal biopsy by C3 deposition, alone or with scanty immunoglobulins, as well as by an electron-dense material in mesangium, subendothelial and subepithelial space
The co-existence of C3 glomerulopathy in a patient with Cystic fibrosis (CF), which is characterized by chronic infection/ inflammation, makes this case an interesting model of chronic altered systemic activation of the alternative pathway of the complement cascade
Summary
C3 glomerulonephritis (C3GN) has been recently included with Dense Deposit Disease (DDD) in the new entity of C3 glomerulopathy This has been codified to highlight the difference between clearly recognizable secondary forms of membranoproliferative glomerulonephritis (MPGN) and those idiopathic cases lacking the classical staining for immunoglobulin at immunofluorescence (IF). The deposits were well characterized by electron microscopy They were localized to a greater extent in mesangium, but the assay demonstrated their presence in subendothelial and subepithelial spaces. Their confluent electrondense appearance, instead of the intensely osmiophilic ribbon-shaped deposits pathognomonic for DDD, allowed to conclude for a C3 glomerulonephritis (Fig. 3a and b). After two years of disease her renal function is stable with serum creatinine 1.7 mg/dl, creatinine clearance 50 ml/min, 24 h proteinuria 270 mg, hypocomplementemia for C3 (14 mg/dl) and haemoglobin 9.4 mg/dl
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