Recurrent Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits in Kidney Allografts Treated With Anti-CD20 Antibodies

Anna Buxeda, Samar M. Said, Samih H. Nasr, Nelson Leung, Mireille El Ters, Fernando G Cosio

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a distinct form of glomerulonephritis 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 immunoglobulin) occurred in 18 of 20 recipients (90%), a median of 7 (1 to 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 patients with recurrences were treated with cyclophosphamide with or without plasmapheresis, and 2 of these grafts were lost from glomerulonephritis. Nine patients with recurrences were treated with anti-CD20 antibodies (rituximab) alone, resulting in improvements in estimated glomerular filtration rate (31.5 ± 16 versus 38.8 ± 13.3 mL/min/1.73 m, P = 0.011) and proteinuria (1280 [117 to 3752] versus 168 [83 to 1613] mg/24 h, P = 0.012) although complete clinical remission was rare. One graft in this later group was lost from recurrence 141 months post transplant. Posttreatment biopsies demonstrated stable or improved glomerular histology in most cases. However, PGNMID did not resolve in any case. Four patients received rituximab 4 months pretransplant 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 pretransplant rituximab modifies the course of recurrence requires additional studies.

Original languageEnglish (US)
Pages (from-to)1477-1485
Number of pages9
JournalTransplantation
Volume103
Issue number7
DOIs
StatePublished - Jul 1 2019

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Glomerulonephritis
Allografts
Immunoglobulins
Anti-Idiotypic Antibodies
Kidney
Recurrence
Transplants
Biopsy
Plasmapheresis
Graft Survival
Clinical Protocols
Glomerular Filtration Rate
Proteinuria
Kidney Transplantation
Cyclophosphamide
Histology
Light
Rituximab

ASJC Scopus subject areas

  • Transplantation

Cite this

Recurrent Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits in Kidney Allografts Treated With Anti-CD20 Antibodies. / Buxeda, Anna; Said, Samar M.; Nasr, Samih H.; Leung, Nelson; El Ters, Mireille; Cosio, Fernando G.

In: Transplantation, Vol. 103, No. 7, 01.07.2019, p. 1477-1485.

Research output: Contribution to journalArticle

Buxeda, Anna ; Said, Samar M. ; Nasr, Samih H. ; Leung, Nelson ; El Ters, Mireille ; Cosio, Fernando G. / Recurrent Proliferative Glomerulonephritis With Monoclonal Immunoglobulin Deposits in Kidney Allografts Treated With Anti-CD20 Antibodies. In: Transplantation. 2019 ; Vol. 103, No. 7. pp. 1477-1485.
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abstract = "BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a distinct form of glomerulonephritis 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 immunoglobulin) occurred in 18 of 20 recipients (90{\%}), a median of 7 (1 to 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 patients with recurrences were treated with cyclophosphamide with or without plasmapheresis, and 2 of these grafts were lost from glomerulonephritis. Nine patients with recurrences were treated with anti-CD20 antibodies (rituximab) alone, resulting in improvements in estimated glomerular filtration rate (31.5 ± 16 versus 38.8 ± 13.3 mL/min/1.73 m, P = 0.011) and proteinuria (1280 [117 to 3752] versus 168 [83 to 1613] mg/24 h, P = 0.012) although complete clinical remission was rare. One graft in this later group was lost from recurrence 141 months post transplant. Posttreatment biopsies demonstrated stable or improved glomerular histology in most cases. However, PGNMID did not resolve in any case. Four patients received rituximab 4 months pretransplant 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 pretransplant rituximab modifies the course of recurrence requires additional studies.",
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AU - Cosio, Fernando G

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N2 - BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a distinct form of glomerulonephritis 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 immunoglobulin) occurred in 18 of 20 recipients (90%), a median of 7 (1 to 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 patients with recurrences were treated with cyclophosphamide with or without plasmapheresis, and 2 of these grafts were lost from glomerulonephritis. Nine patients with recurrences were treated with anti-CD20 antibodies (rituximab) alone, resulting in improvements in estimated glomerular filtration rate (31.5 ± 16 versus 38.8 ± 13.3 mL/min/1.73 m, P = 0.011) and proteinuria (1280 [117 to 3752] versus 168 [83 to 1613] mg/24 h, P = 0.012) although complete clinical remission was rare. One graft in this later group was lost from recurrence 141 months post transplant. Posttreatment biopsies demonstrated stable or improved glomerular histology in most cases. However, PGNMID did not resolve in any case. Four patients received rituximab 4 months pretransplant 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 pretransplant rituximab modifies the course of recurrence requires additional studies.

AB - BACKGROUND: Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a distinct form of glomerulonephritis 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 immunoglobulin) occurred in 18 of 20 recipients (90%), a median of 7 (1 to 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 patients with recurrences were treated with cyclophosphamide with or without plasmapheresis, and 2 of these grafts were lost from glomerulonephritis. Nine patients with recurrences were treated with anti-CD20 antibodies (rituximab) alone, resulting in improvements in estimated glomerular filtration rate (31.5 ± 16 versus 38.8 ± 13.3 mL/min/1.73 m, P = 0.011) and proteinuria (1280 [117 to 3752] versus 168 [83 to 1613] mg/24 h, P = 0.012) although complete clinical remission was rare. One graft in this later group was lost from recurrence 141 months post transplant. Posttreatment biopsies demonstrated stable or improved glomerular histology in most cases. However, PGNMID did not resolve in any case. Four patients received rituximab 4 months pretransplant 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 pretransplant rituximab modifies the course of recurrence requires additional studies.

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