Abstract: SA-PO226
The Clone Wars: Evolving Treatment of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin G Deposits
Session Information
- Trainee Case Reports - V
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Manohar, Sandhya, Mayo Clinic , Rochester, Minnesota, United States
- Leung, Nelson, Mayo Clinic , Rochester, Minnesota, United States
Introduction
Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) is a recently described entity and as we become more aware of this in our patients, its treatment poses the next challenge. Here we present a patient we cared for and the dynamic changes in his response to therapy that helped us guide his treatment regimen.
Case Description
A 63 year old male was found to have 8 g/d proteinuria and chronic kidney disease at the time of a cardiac evaluation 14 years ago. Kidney biopsy was reported elsewhere as membranous nephropathy and was treated initially with cyclophosphamide (C ) and prednisone(P) with improvement in his proteinuria down to 3 g/d. Rituximab ( R) was added with improvement in proteinuria to 1 g/d but was not continued due to coverage issues, and was eventually maintained on cyclosporine. He came to us for a second opinion and the diagnosis of PGNMID was made with no evidence of systemic disease. His kidneys eventually failed and he underwent a deceased donor kidney transplant. After 4 years he developed proteinuria of 800mg/d. Kidney allograft biopsy showed recurrence of PGNMID with same IgG kappa. Serology and bone marrow was negative but flow cytometry showed rare polyclonal plasma cells. He was treated with Rituximab initially with improvement in proteinuria down to 267mg/d but slowly increased to 1.1g/d after 3 months despite negative CD20. RCP was given with a more sustained response and his treatment was changed to be directed at CD38 cells with Rituximab and bortezomib (V) for a likely LPL clone with continued improvement in proteinuria.
Discussion
PGNMID in native kidney can be indolent but post-transplant it is usually aggressive and hence need prompt clone-directed therapy. The clones capable of producing PGNMID are plasma cell, lymphoplasmacytic (LPL) clone, and CLL clone. Our patient had no confirmed clone. Initial response to Rituximab suggests that it was a CD20 clone but he progressed and the regimen of RCP was given to knock out cells affecting both CD20 and CD38. His initial response to rituximab and quick recurrence is suggestive that he may have an LPL clone with CD38 cells that are more difficult to eradicate and considering his prior cytoxan exposure was switched to a bortezomib based regimen.The choice of therapy can be difficult, requiring a deeper understanding of PGNMID disease process.