C3 glomerulopathy in cystic fibrosis: a casereport

Background:C3 glomerulonephritis is a rare glomerulopathy characterized at renal biopsy by C3 deposition, aloneor with scanty immunoglobulins, as well as by an electron-dense material in mesangium, subendothelial andsubepithelial space. An abnormal systemic activation of the alternative pathway of the complement cascade isresponsible for the development of the disease if triggered by several possible environmental conditions. Wereport the first case in literature of a patient affected by cystic fibrosis and C3GN.Case presentation:Our 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 C3glomerulopathy. Complement system dysregulation was tested and resulted in a strong terminal pathway activationproved by high levels of sC5b-9 complex, amounting to 1588 ng/ml (normal value < 400 ng/ml). Next generationsequencing (NGS) showed polymorphism inCFH(p.V62I in SCR1) andTHBD(p.A473V), already known as pathogenicfor C3GN, as well as a mutation inC3(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).Conclusions:The 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 ofthe complement cascade.