A STEINBERG1, N BARRACLOUGH2, P HILL3, K DWYER4, D GOODMAN1, FIERINO1
1Department of Nephrology, St Vincent’s Hospital Melbourne, Fitzroy, Australia, 2Warrnambool Base Hospital, Warrnambool , Australia, 3Department of Anatomical Pathology, St Vincent’s Hospital Melbourne, Fitzroy, Australia, 4School of Medicine, Deakin University, Geelong, Australia
Background: Membranoproliferative glomerulonephritis (MPGN) arising post transplantation can represent de novo disease or recurrence and may be idiopathic or secondary to viral infections, autoimmune disease and malignancy. An accurate diagnosis is critical to guide management and preserve graft function.
Case Report: A forty-five year old male with end-stage renal disease of unknown aetiology received a transplant from his father in 2009 with baseline serum creatinine 150µmol/L, maintained on standard immunosuppression. He developed non-nephrotic range proteinuria (urinary albumin-creatinine ratio [uACR]198mg/mmol) and microscopic haematuria. A diagnostic transplant renal biopsy demonstrated MPGN; immunofluorescence was positive for IgG kappa and lambda light chains without restriction, C3 and C1q; IgM and IgA were negative. Electron microscopy confirmed immune deposits. Hepatitis B and C, ANA and ANCA were negative. C3 was reduced at 0.58 g/L (normal 0.9-1.8); C4 was within normal range. Serum kappa free light chains were elevated (446 mg/L; normal 3.3-19.4) with an increased ratio (13.4). Bone marrow aspirate revealed a mild plasmacytosis (5-10%). He was treated with high-dose prednisolone and cyclophosphamide but failed to respond with progressive proteinuria and rising creatinine (peak 399µmol/L). Repeat biopsy again demonstrated MPGN with increasing immune-type deposits. Targeted B-cell therapy with rituximab (two 1000mg doses) was administered with a clinical response evidenced by an improving creatinine to 198µmol/L, and reduction in proteinuria (uACR 102mg/mmol).
Conclusion: Although the bone marrow aspirate was not diagnostic, the light-chain paraproteinaemia and increasing immune-type deposits on biopsy implicate a primary underlying B-cell clonal disease. The failure to respond to non-specific immunosuppression and the response to rituximab supports this premise. This case demonstrates the need to better understand mechanisms underlying disease processes to facilitate the delivery of personalised therapy.
Adam is a second-year advanced trainee in nephrology.