Crescentic immunoglobulin a nephropathy with positive anti-neutrophil cytoplasmic antibodies: A rare combination

Abstract

Background: Immunoglobulin A Nephropathy (IgAN) is generally a slowly progressive disease, with less than 10% of patients presenting with rapidly progressive glomerulonephritis (RPGN). We report a rare case of severe crescentic IgAN with positive circulating antineutrophil cytoplasmic autoantibodies (ANCA). Case Report: A 64-year-old female presented with acute kidney injury (AKI) and peripheral oedema on a background of type 2 diabetes mellitus, hypertension, sarcoidosis, monoclonal gammopathy of undetermined significance (MGUS), and stage 3B chronic kidney disease (CKD). Serum creatinine peaked at 404 mumol/L with an eGFR of 10 ml/min/1.73 m2 during admission. Urine albumin/creatinine ratio (ACR) was 380 mg/mmol, with significant microhaematuria (660 x 106/L erythrocytes). Nephrotoxic agents were withheld, and furosemide was commenced to manage fluid overload. Intravenous methylprednisolone pulse was given for suspected primary glomerular pathology. Renal biopsy showed 16 glomeruli, six with fibrocellular crescents. Immunofluorescence showed mesangial and capillary granular staining with IgA and C3. The diagnosis of IgAN was subsequently made. She was commenced on prednisolone 80 mg daily and discharged. Subsequently, ANCA returned as positive with elevated antimyeloperoxidase (MPO) titre of 7.8 AI. Autoimmune and viral screen was otherwise unremarkable. Four weeks later, creatinine remained elevated at 416 mumol/L, with urine ACR 398 mg/mmol. Based on poor steroid response, crescents on biopsy, and ANCA positivity, she was treated with intravenous cyclophosphamide for 6 months. Renal function improved rapidly and at 6 months creatinine was 211 mumol/L, urine ACR 79 mg/mmol, and ANCA was negative. She was maintained on low dose azathioprine and prednisolone. Conclusion(s): ANCA-positive IgAN is a rare, severe disease phenotype which has greater response to immunosuppression than ANCAnegative IgAN. Clinicians should consider measurement of ANCA in IgAN patients with RPGN, as immunosuppression therapy in this patient cohort could vastly improve outcomes.