Recurrent proliferative glomerulonephritis with monoclonal immunoglobulin deposits in kidney allografts treated with anti-cd20 antibodies

Background: proliferative glomerulonephritis with monoclonal immunoglobulin (Ig) deposits (PGNMID) is a distinct form of glomerulonephritis (GN) that often recurs after kidney transplantation causing severe graft injury and often failure. Methods: we describe post-transplant outcomes and response to therapy in 20 recipients with PGNMID. Evidence of PGNMID recurrence or lack thereof was determined by protocol and clinical biopsies. Results: histologic recurrence (deposition of monoclonal Ig) occurred in 18 of 20 recipients (90%) a median of 7 (1-65) months post-transplant. At diagnosis, recurrence was generally associated with mild or no clinical manifestations and often with mild glomerular morphologic changes by light microcopy. Four of the 18 patients with recurrence did not progress and were not treated. Another 4 recurrences were treated with cyclophosphamide and/or plasmapheresis and two of these grafts were lost from GN. Nine recurrences were treated with anti-CD20 antibodies (rituximab) alone resulting in improvements in estimated glomerular filtration rate (eGFR) (31.5±16 versus 38.8±13.3 ml/min/1.73 m2, p=0.011) and proteinuria [1280 (117-3752) mg/24h versus 168 (83-1613), p=0.012] although complete clinical remission was rare. One graft in this later group was lost from recurrence 141 months post-transplant. Post-treatment biopsies demonstrated stable or improved glomerular histology in most cases. However, PGNMID did not resolve in any case. Four patients received rituximab 4 months pre-transplant aimed to prevent recurrence. However, 3 had mild recurrences. Conclusions: rituximab treatment of early PGNMID recurrence is effective resulting in reasonable long term graft survival. Whether pre-transplant rituximab modifies the course of recurrence requires additional studies. The authors declare no conflicts of interest This research was funded via internal Mayo Clinic grants. Address correspondence to: Fernando G. Cosio, MD, Mayo Clinic, 200 First Street SW, Rochester, MN. 55905, Phone: (507) 266-1963; Fax: (507) 266-7891, E-mail: cosio.fernando@mayo.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

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