Rapidly Progressive Glomerulonephritis with ANCA and Anti-GBM Antibodies in the setting of Acute Dengue Infection

Rapidly progressive glomerulonephritis (RPGN) is the acute loss of renal function due to deposition of anti-glomerular basement membrane (GBM) antibodies, immune complexes, and/or antineutrophil cytoplasmic antibodies... [ view full abstract ]

Rapidly progressive glomerulonephritis (RPGN) is the acute loss of renal function due to deposition of anti-glomerular basement membrane (GBM) antibodies, immune complexes, and/or antineutrophil cytoplasmic antibodies (ANCAs), causing intra-glomerular inflammation. Being doubly positive for ANCA and anti-GBM is exceedingly rare and carries a poorer prognosis. Molecular mimicry has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A 66 year-old Honduran woman presented to our institution for further evaluation of suspected RPGN.  A month prior, she experienced nausea, dysgeusia, and progressive fatigue. She also suffered from mosquito bites. She was admitted to a Honduran hospital with frothy, blood-tinged urine and bilateral palpebral edema. Laboratory values showed hemoglobin (Hgb) 9.7 g/dL (baseline 13.6 g/dL), serum creatinine (Cr) 6.1 mg/dL (baseline 0.74 mg/dL) and microscopic hematuria and proteinuria 1.2 gm/day.  Renal biopsy showed cellular crescents with positive anti-GBM antibodies, ANCA Myeloperoxidase (MPO) and anti-dengue IgM antibodies.  Thus she was diagnosed with RPGN and acute dengue infection, started on systemic corticosteroids and cyclophosphamide and transferred to our institution for further management. On arrival, the patient had no hemoptysis or evidence of pulmonary hemorrhage. Patient was initiated on plasmapheresis, prednisone and cyclophosphamide.  Treatment was complicated by progressive anemia (Hgb 6.6 g/dL), thrombocytopenia (platelets 62 K/mcl), and a coagulopathy (international normalized ratio (INR) 1.7) that developed after her fifth course of plasmapheresis. Normal peripheral smear and additional labs excluded hemolysis, but confirmed a shearing effect secondary to plasmapheresis.  After 14 total sessions of plasmapheresis and supportive transfusions, repeat renal biopsy showed progression from acute to chronic phase of disease.  Before discharge, Hgb 10.4 g/dL, platelets 6 K/mcl, Cr 4.3 mg/dL, INR 1.2 and antibody titers undetectable. This demonstrates a unique case of MPO and ANCA mediated anti-GBM disease, in the setting of acute dengue, managed with plasmapheresis, prednisone and cyclophosphamide. Newfound thrombocytopenia and anemia secondary to plasmapheresis complicated management of this insidious renal failure.