K HEPBURN1,2, E MILLAR2,3, J KELLY1,2, I KATZ1,2
1Department of Renal Medicine, St George Hospital, Kogarah, Australia, 2St George Clinical School UNSW, St George Hospital, Kogarah, Australia, 3Department of Anatomical Histopathology, St George Hospital, Kogarah, Australia
Background: Anti-Glomerular basement membrane (anti-GBM) disease is a rare glomerulonephritis where IgG autoantibodies cause destruction of the glomerular basement membrane and a rapidly progressive GN. Atypical anti-GBM disease, a rare variant with undetectable serum anti-GBM antibodies, differing histopathology, and possibly a subacute course, has been reported in a limited number of case reports and series.
Case Report: A 23-year-old male was referred by his GP, with unexpected renal impairment with creatinine of 220µmol/L and eGFR 35ml/min/1.73m2, nephrotic range proteinuria (6.5g/24hr), hypoalbuminaemia (albumin 29) and elevated cholesterol of 10mmol/L. He was asymptomatic with no peripheral oedema, and no significant background medical history, except a 2-pack-year smoking history. Autoimmune screen, ANCA, IEPG, Hepatitis B, C and HIV were negative. Renal biopsy showed strongly positive linear IgG on immunofluorescence indicating anti-GBM disease, with advanced chronic nodular mesangial sclerosing proliferative glomerulonephritis, with occasional crescents and moderate interstitial fibrosis in keeping with “atypical” anti-GBM glomerulonephritis. Electron microscopy confirmed the diagnosis of anti-GBM disease, also noting mesangial expansion and ischaemic wrinkling of glomerular basement membranes. Serum IgG Anti-GBM antibodies using fluorescence enzyme immunoassay were negative. He received pulsed and oral steroids, IV cyclophosphamide and plasmapheresis. Unfortunately, the patient’s renal function did not improve. His current creatinine is 264umol/L and eGFR 28ml/min/1.73m2. His anti-GBM antibodies remain negative.
Conclusions: Atypical anti-GBM disease is characterised by undetectable serum anti-GBM antibodies and can have a range of histopathological features including focal crescents, nodular glomerulosclerosis, proliferative glomerulonephritis, and glomerular microangiopathy. Our case adds to the literature on this rare entity, highlighting that negative anti-GBM antibodies may not always exclude anti-GBM disease and that renal biopsy remains essential to diagnosis.
Dr Kirsten Hepburn is a second year Nephrology Advanced Trainee in the East Coast Renal Network, NSW. Her other degrees include BSc (Psych) and MPH.