E CHUNG1, K MCILROY1, C FUNG2, S SESHAN3, P COLEMAN4
1Royal North Shore Hospital, Sydney, Australia, 2Concord Repatriation General Hospital, Sydney, Australia, 3Weill Cornell Medical College , New York, United States of America, 4Manly Hospital, Sydney, Australia
Background: Plasma cell dyscrasias are characterised by overproduction of monoclonal proteins which can cause a wide range of kidney diseases. Whilst the majority of pathogenic light-chains are tubulopathic, in a minority of cases reabsorption of light-chains in the proximal tubules can cause intracellular crystal deposits or inclusion bodies. The accumulation of fibrillary cytoplasmic inclusions causing proximal tubulopathy has only been described in two previous cases. We report a case of persistent proteinuria without acute kidney injury, with abnormal accumulation of cytoplasmic fibrillary inclusions on kidney biopsy.
Case Report: A 59-year old man with IgA κ paraproteinemia was investigated for worsening proteinuria (2.4g to 4.8g in 24 hours) with stable renal function (serum creatinine 110 µmol/L) from 2012 to 2014. A renal biopsy showed extensive tubular vacuolation and focal fibrillar structures on the Masson stain, suggesting intracytoplasmic fibrillary deposition related to the known paraproteinemia. Insitu hybridisation and immunoperoxidase staining for κ and λ light chains were negative. Electron microscopy showed abnormal fibrils (10nm diameter) in the lysosomes of mesangial cells, glomerular endothelial cells and tubular cells. A bone marrow aspirate showed 46% monoclonal plasma cells. The diagnosis of multiple myeloma with light chain-associated proximal tubulopathy was made. Five rounds of cyclophosphamide, bortezomib and dexamethasone chemotherapy followed by a syngeneic stem cell transplant was performed in 2015, resulting in clinical remission of his multiple myeloma and improvement of his proteinuria to 0.36g/day by 2017.
Conclusions: Accumulation of fibrillary material on electron microscopy, while rare, is strongly suggestive of plasma cell dyscrasias and should direct clinicians to perform further haematological investigations to confirm the diagnosis of plasma cell dyscrasias.
Edmund Chung is currently a first year renal advanced trainee in the East Coast Network, NSW. He completed his undergraduate BMed MD at UNSW and postgraduate MMed (ClinEpi) at the University of Sydney. He has performed systematic reviews with the Cochrane Kidney and Transplant group and is passionate about better understanding how to limit the progression of chronic kidney disease.