C3 glomerulopathy associated with monoclonal Ig is a distinct subtype

Aishwarya Ravindran, Fernando Custodio Fervenza, Richard J.H. Smith, Sanjeev M Sethi

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Monoclonal immunoglobulins (MIg) may play a causal role in C3 glomerulopathy (C3G) by impairing regulation of the alternative pathway of complement. Ninety-five patients with C3G were tested for MIg of which 36 were positive. Their mean age at diagnosis was 60 years and among patient 50 years and older, 65.1% had a MIg. At presentation, median serum creatinine and proteinuria were 1.9 mg/dL and 3.0 g/24 hours. Hematuria was present in 32 (88.9%) patients. Twelve (34.3%) patients had low C3 levels. C3 nephritic factor was detected in 45.8% patients; pathogenic variants in complement protein genes were rare. Hematologic evaluation revealed monoclonal gammopathy of renal significance in 26 patients, multiple myeloma in five, smoldering multiple myeloma in two, and chronic lymphocytic leukemia, lymphoma, or type I cryoglobulin each in one patient. After a median follow-up of 43.6 months, the median serum creatinine and proteinuria were 1.4 mg/dL and 0.8g/24 hours. Nine patients developed ESRD. Sixteen patients received MIg-targeted treatment, 17 patients received non-targeted treatment while three patients were managed conservatively. Of the 16 patients receiving MIg-targeted treatment, ten achieved complete/very good/partial hematologic response. Of these, seven achieved a complete/partial/stable renal response. Five patients receiving targeted treatment did not achieve hematologic response, none had a renal response. Patients receiving targeted treatment were more likely to have multiple myeloma/smoldering multiple myeloma. Patients receiving non-targeted treatment were more likely to have monoclonal gammopathy of renal significance. Thus, C3G with MIg is seen in older patients, C3 nephritic factor is the most common autoantibody detected, and MIg-targeted treatment may result in remission and stabilization of kidney function in a subset of these patients.

Original languageEnglish (US)
JournalKidney International
DOIs
StateAccepted/In press - Jan 1 2018

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Immunoglobulins
Multiple Myeloma
Complement C3 Nephritic Factor
Kidney
Paraproteinemias
B-Cell Chronic Lymphocytic Leukemia
Proteinuria
Therapeutics
Creatinine
Cryoglobulins
Alternative Complement Pathway
Hematuria
Serum
Autoantibodies
Chronic Kidney Failure
Complement System Proteins
Genes

Keywords

  • alternative pathway of complement
  • C3 glomerulonephritis
  • C3 glomerulopathy
  • dense deposit disease
  • monoclonal Ig

ASJC Scopus subject areas

  • Nephrology

Cite this

C3 glomerulopathy associated with monoclonal Ig is a distinct subtype. / Ravindran, Aishwarya; Fervenza, Fernando Custodio; Smith, Richard J.H.; Sethi, Sanjeev M.

In: Kidney International, 01.01.2018.

Research output: Contribution to journalArticle

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abstract = "Monoclonal immunoglobulins (MIg) may play a causal role in C3 glomerulopathy (C3G) by impairing regulation of the alternative pathway of complement. Ninety-five patients with C3G were tested for MIg of which 36 were positive. Their mean age at diagnosis was 60 years and among patient 50 years and older, 65.1{\%} had a MIg. At presentation, median serum creatinine and proteinuria were 1.9 mg/dL and 3.0 g/24 hours. Hematuria was present in 32 (88.9{\%}) patients. Twelve (34.3{\%}) patients had low C3 levels. C3 nephritic factor was detected in 45.8{\%} patients; pathogenic variants in complement protein genes were rare. Hematologic evaluation revealed monoclonal gammopathy of renal significance in 26 patients, multiple myeloma in five, smoldering multiple myeloma in two, and chronic lymphocytic leukemia, lymphoma, or type I cryoglobulin each in one patient. After a median follow-up of 43.6 months, the median serum creatinine and proteinuria were 1.4 mg/dL and 0.8g/24 hours. Nine patients developed ESRD. Sixteen patients received MIg-targeted treatment, 17 patients received non-targeted treatment while three patients were managed conservatively. Of the 16 patients receiving MIg-targeted treatment, ten achieved complete/very good/partial hematologic response. Of these, seven achieved a complete/partial/stable renal response. Five patients receiving targeted treatment did not achieve hematologic response, none had a renal response. Patients receiving targeted treatment were more likely to have multiple myeloma/smoldering multiple myeloma. Patients receiving non-targeted treatment were more likely to have monoclonal gammopathy of renal significance. Thus, C3G with MIg is seen in older patients, C3 nephritic factor is the most common autoantibody detected, and MIg-targeted treatment may result in remission and stabilization of kidney function in a subset of these patients.",
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