C3 glomerulopathy in adults: A distinct patient subset showing frequent association with monoclonal gammopathy and poor renal outcome

Isaac E. Lloyd, Alexander Gallan, Hunter K. Huston, Kalani L. Raphael, Dylan V. Miller, Monica P. Revelo, Mazdak Khalighi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background: C3 glomerulopathy (C3G) includes both C3 glomerulonephritis (C3GN) and dense deposit disease (DDD) and is defined by C3-dominant deposits on immunofluorescence. Dysfunction of the alternative pathway (AP) of complement is central to the pathophysiology of C3G and young patients often harbor genetic alterations of AP mediators. Recently, a link between C3G and paraproteinemia has been established.We performed this study to better characterize older patients with C3G where this association is more frequently seen. Methods: Fourteen biopsies from 12 patients meeting diagnostic criteria for C3G were identified in patients >49 years of age from 2005 to 2015 after exclusion of cases containing masked monotypic immunoglobulin deposits. Pathologic and clinical features were reviewed. Results: The median age was 63.5 years and 75% of patients were male. All had renal insufficiency at presentation. Kidney biopsy showed DDD in three patients and C3GN in the remainder. Serum protein electrophoresis revealed a paraprotein in 10 patients, 8 of which had a plasma cell dyscrasia on bone marrow biopsy. A membranoproliferative pattern of glomerular injury was seen in 64% of biopsies, while mesangial proliferative and endocapillary proliferative patterns were seen less frequently. Among patients with at least 1 year of follow-up (n = 9), five were on renal replacement therapy, three showed stable (but impaired) kidney function and one demonstrated improvement. Conclusions: C3G is an uncommon but important cause of kidney injury in older adults and associates with a high prevalence of paraproteinemia. In adult patients with C3G, prognosis is guarded as most patients showed either progression to end-stage kidney disease or stable but impaired kidney function.

Original languageEnglish (US)
Pages (from-to)794-799
Number of pages6
JournalClinical Kidney Journal
Volume9
Issue number6
DOIs
StatePublished - Jan 1 2016
Externally publishedYes

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Paraproteinemias
Kidney
Membranoproliferative Glomerulonephritis
Biopsy
Glomerulonephritis
Paraproteins
Alternative Complement Pathway
Renal Replacement Therapy
Wounds and Injuries
Chronic Kidney Failure
Renal Insufficiency
Fluorescent Antibody Technique
Electrophoresis
Immunoglobulins
Blood Proteins
Bone Marrow

Keywords

  • Alternative pathway
  • C3 glomerulopathy
  • Monoclonal gammopathy

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

C3 glomerulopathy in adults : A distinct patient subset showing frequent association with monoclonal gammopathy and poor renal outcome. / Lloyd, Isaac E.; Gallan, Alexander; Huston, Hunter K.; Raphael, Kalani L.; Miller, Dylan V.; Revelo, Monica P.; Khalighi, Mazdak.

In: Clinical Kidney Journal, Vol. 9, No. 6, 01.01.2016, p. 794-799.

Research output: Contribution to journalArticle

Lloyd, Isaac E. ; Gallan, Alexander ; Huston, Hunter K. ; Raphael, Kalani L. ; Miller, Dylan V. ; Revelo, Monica P. ; Khalighi, Mazdak. / C3 glomerulopathy in adults : A distinct patient subset showing frequent association with monoclonal gammopathy and poor renal outcome. In: Clinical Kidney Journal. 2016 ; Vol. 9, No. 6. pp. 794-799.
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T2 - A distinct patient subset showing frequent association with monoclonal gammopathy and poor renal outcome

AU - Lloyd, Isaac E.

AU - Gallan, Alexander

AU - Huston, Hunter K.

AU - Raphael, Kalani L.

AU - Miller, Dylan V.

AU - Revelo, Monica P.

AU - Khalighi, Mazdak

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N2 - Background: C3 glomerulopathy (C3G) includes both C3 glomerulonephritis (C3GN) and dense deposit disease (DDD) and is defined by C3-dominant deposits on immunofluorescence. Dysfunction of the alternative pathway (AP) of complement is central to the pathophysiology of C3G and young patients often harbor genetic alterations of AP mediators. Recently, a link between C3G and paraproteinemia has been established.We performed this study to better characterize older patients with C3G where this association is more frequently seen. Methods: Fourteen biopsies from 12 patients meeting diagnostic criteria for C3G were identified in patients >49 years of age from 2005 to 2015 after exclusion of cases containing masked monotypic immunoglobulin deposits. Pathologic and clinical features were reviewed. Results: The median age was 63.5 years and 75% of patients were male. All had renal insufficiency at presentation. Kidney biopsy showed DDD in three patients and C3GN in the remainder. Serum protein electrophoresis revealed a paraprotein in 10 patients, 8 of which had a plasma cell dyscrasia on bone marrow biopsy. A membranoproliferative pattern of glomerular injury was seen in 64% of biopsies, while mesangial proliferative and endocapillary proliferative patterns were seen less frequently. Among patients with at least 1 year of follow-up (n = 9), five were on renal replacement therapy, three showed stable (but impaired) kidney function and one demonstrated improvement. Conclusions: C3G is an uncommon but important cause of kidney injury in older adults and associates with a high prevalence of paraproteinemia. In adult patients with C3G, prognosis is guarded as most patients showed either progression to end-stage kidney disease or stable but impaired kidney function.

AB - Background: C3 glomerulopathy (C3G) includes both C3 glomerulonephritis (C3GN) and dense deposit disease (DDD) and is defined by C3-dominant deposits on immunofluorescence. Dysfunction of the alternative pathway (AP) of complement is central to the pathophysiology of C3G and young patients often harbor genetic alterations of AP mediators. Recently, a link between C3G and paraproteinemia has been established.We performed this study to better characterize older patients with C3G where this association is more frequently seen. Methods: Fourteen biopsies from 12 patients meeting diagnostic criteria for C3G were identified in patients >49 years of age from 2005 to 2015 after exclusion of cases containing masked monotypic immunoglobulin deposits. Pathologic and clinical features were reviewed. Results: The median age was 63.5 years and 75% of patients were male. All had renal insufficiency at presentation. Kidney biopsy showed DDD in three patients and C3GN in the remainder. Serum protein electrophoresis revealed a paraprotein in 10 patients, 8 of which had a plasma cell dyscrasia on bone marrow biopsy. A membranoproliferative pattern of glomerular injury was seen in 64% of biopsies, while mesangial proliferative and endocapillary proliferative patterns were seen less frequently. Among patients with at least 1 year of follow-up (n = 9), five were on renal replacement therapy, three showed stable (but impaired) kidney function and one demonstrated improvement. Conclusions: C3G is an uncommon but important cause of kidney injury in older adults and associates with a high prevalence of paraproteinemia. In adult patients with C3G, prognosis is guarded as most patients showed either progression to end-stage kidney disease or stable but impaired kidney function.

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