CONTRASTING PRESENTATIONS OF ALEMTUZUMAB INDUCED ANTI-GLOMERULAR BASEMENT MEMBRANE DISEASE AND POTENTIAL IMPLICATIONS

E VAUGHAN1, A TIKU1, C POLLOCK1,2
1Royal North Shore Hospital, St Leonards, Australia, 2Kolling Insitute of Medical Research, St Leonards, Australia

Background: Alemtuzumab, an anti-CD52 pan-lymphocyte depleting monoclonal antibody approved for management of relapsing-remitting multiple sclerosis (MS) has been associated with the rare occurrence of immune-mediated toxicities, including anti-glomerular basement membrane (GBM) disease and subsequent end stage kidney disease (ESKD). We report two contrasting presentations of this rare phenomenon.
Case Report: A 42-year-old woman presented with macroscopic haematuria and acute kidney injury (creatinine 359umol/L) three years post Alemtuzumab treatment for MS.  Anti-GBM antibody titre was 480units/mL (normal <7).  Renal biopsy confirmed crescentic glomerulonephritis with strong linear IgG staining on immunofluorescence.  She was managed with high dose steroids, cyclophosphamide, plasma exchange and Rituximab, but progressed to ESKD requiring dialysis with no recovery of renal function three months later. A 42-year-old man was referred for investigation of new microscopic haematuria with normal creatinine (66umol/L), detected on screening post Alemtuzumab for MS.  Renal biopsy undertaken based on an erroneously elevated albumin-creatinine ratio (ACR) of 400 mg/mmol was normal to light microscopy; however, immunofluorescence was strongly positive with linear IgG deposition consistent with anti-GBM disease. Anti GBM titre was 4.4units/mL and amended ACR 4mg/mmol. He was managed with high dose steroids, mycophenolate, plasma exchange and Rituximab and maintains normal renal function.
Conclusions: We have described significant variability in the presentation of anti-GBM disease post Alemtuzumab. This poses challenges in identifying patients who will have an aggressive disease course and may rely on understanding the mechanism underpinning phenotypic variability of anti-GBM disease. Ramifications include over-treating inactive disease or under-treating destructive immune-mediated nephritis.  Incorporating routine renal biopsies into monitoring strategies for all patients on Alemtuzumab for MS may increase our understanding of anti-GBM disease heterogeneity and burden to guide future therapeutic strategies.


Biography:
Renal Advanced Trainee, Royal North Shore Hospital.

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