C3 glomerulonephritis associated with monoclonal gammopathy: A case series

Ladan Zand, Andrea Kattah, Fernando Custodio Fervenza, Richard J H Smith, Samih H. Nasr, Yuzhou Zhang, Julie A. Vrana, Nelson Leung, Lynn D. Cornell, Sanjeev M Sethi

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Abstract

Background: C3 glomerulonephritis (GN) is a proliferative GN resulting from glomerular deposition of complement factors due to dysregulation of the alternative pathway of complement. Dysregulation of the alternative pathway of complement may occur as a result of mutations or functional inhibition of complement-regulating proteins. Functional inhibition of the complement-regulating proteins may result from a monoclonal gammopathy. Study Design: Case series. Setting & Participants: 32 Mayo Clinic patients with C3 GN, 10 (31%) of whom had evidence of a monoclonal immunoglobulin in serum. Outcomes: Clinical features, hematologic and bone marrow biopsy findings, kidney biopsy findings, kidney measures, complement pathway abnormalities, treatment, and follow-up of patients with C3 GN that was associated with a monoclonal gammopathy. Results: Mean age of patients with C3 GN associated with monoclonal gammopathy was 54.5 years. Bone marrow biopsy done in 9 patients revealed monoclonal gammopathy of undetermined significance in 5 patients, small lymphocytic lymphoma/chronic lymphocytic leukemia in one patient, and no abnormal clones in the other 3 patients. Kidney biopsy showed membranoproliferative GN with bright capillary wall C3 staining in all 10 patients. Evaluation of the alternative pathway of complement showed abnormalities in 7 of 9 patients tested. No mutation in complement-regulating proteins was detected in any patient. As an index case, one patient with C3 GN and chronic lymphocytic leukemia was treated with rituximab, cyclophosphamide, vincristine, and prednisone, and one patient with C3 GN and monoclonal gammopathy of undetermined significance was treated with dexamethasone and bortezomib. Both patients showed significant decreases in hematuria and proteinuria and stabilization of kidney function. Limitations: Studies to show evidence of direct activation of the alternative pathway by monoclonal immunoglobulin were not done. Conclusions: The study highlights the association of C3 GN and monoclonal gammopathy, in particular in the older population, and the importance of targeting the underlying hematologic malignancy as an approach to treating C3 GN.

Original languageEnglish (US)
Pages (from-to)506-514
Number of pages9
JournalAmerican Journal of Kidney Diseases
Volume62
Issue number3
DOIs
StatePublished - Sep 2013

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Paraproteinemias
Glomerulonephritis
Alternative Complement Pathway
B-Cell Chronic Lymphocytic Leukemia
Monoclonal Gammopathy of Undetermined Significance
Kidney
Biopsy
Complement System Proteins
Immunoglobulins
Bone Marrow
Membranoproliferative Glomerulonephritis
Mutation
Vincristine
Hematuria
Hematologic Neoplasms
Prednisone
Proteinuria
Cyclophosphamide
Dexamethasone

Keywords

  • C3 Glomerulonephritis (C3 GN)
  • membranoproliferative glomerulonephritis (MPGN)
  • monoclonal gammopathy
  • monoclonal gammopathy of undetermined significance (MGUS)

ASJC Scopus subject areas

  • Nephrology

Cite this

C3 glomerulonephritis associated with monoclonal gammopathy : A case series. / Zand, Ladan; Kattah, Andrea; Fervenza, Fernando Custodio; Smith, Richard J H; Nasr, Samih H.; Zhang, Yuzhou; Vrana, Julie A.; Leung, Nelson; Cornell, Lynn D.; Sethi, Sanjeev M.

In: American Journal of Kidney Diseases, Vol. 62, No. 3, 09.2013, p. 506-514.

Research output: Contribution to journalArticle

Zand, Ladan ; Kattah, Andrea ; Fervenza, Fernando Custodio ; Smith, Richard J H ; Nasr, Samih H. ; Zhang, Yuzhou ; Vrana, Julie A. ; Leung, Nelson ; Cornell, Lynn D. ; Sethi, Sanjeev M. / C3 glomerulonephritis associated with monoclonal gammopathy : A case series. In: American Journal of Kidney Diseases. 2013 ; Vol. 62, No. 3. pp. 506-514.
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AU - Zand, Ladan

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AU - Smith, Richard J H

AU - Nasr, Samih H.

AU - Zhang, Yuzhou

AU - Vrana, Julie A.

AU - Leung, Nelson

AU - Cornell, Lynn D.

AU - Sethi, Sanjeev M

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N2 - Background: C3 glomerulonephritis (GN) is a proliferative GN resulting from glomerular deposition of complement factors due to dysregulation of the alternative pathway of complement. Dysregulation of the alternative pathway of complement may occur as a result of mutations or functional inhibition of complement-regulating proteins. Functional inhibition of the complement-regulating proteins may result from a monoclonal gammopathy. Study Design: Case series. Setting & Participants: 32 Mayo Clinic patients with C3 GN, 10 (31%) of whom had evidence of a monoclonal immunoglobulin in serum. Outcomes: Clinical features, hematologic and bone marrow biopsy findings, kidney biopsy findings, kidney measures, complement pathway abnormalities, treatment, and follow-up of patients with C3 GN that was associated with a monoclonal gammopathy. Results: Mean age of patients with C3 GN associated with monoclonal gammopathy was 54.5 years. Bone marrow biopsy done in 9 patients revealed monoclonal gammopathy of undetermined significance in 5 patients, small lymphocytic lymphoma/chronic lymphocytic leukemia in one patient, and no abnormal clones in the other 3 patients. Kidney biopsy showed membranoproliferative GN with bright capillary wall C3 staining in all 10 patients. Evaluation of the alternative pathway of complement showed abnormalities in 7 of 9 patients tested. No mutation in complement-regulating proteins was detected in any patient. As an index case, one patient with C3 GN and chronic lymphocytic leukemia was treated with rituximab, cyclophosphamide, vincristine, and prednisone, and one patient with C3 GN and monoclonal gammopathy of undetermined significance was treated with dexamethasone and bortezomib. Both patients showed significant decreases in hematuria and proteinuria and stabilization of kidney function. Limitations: Studies to show evidence of direct activation of the alternative pathway by monoclonal immunoglobulin were not done. Conclusions: The study highlights the association of C3 GN and monoclonal gammopathy, in particular in the older population, and the importance of targeting the underlying hematologic malignancy as an approach to treating C3 GN.

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