Abstract: TH-PO005

Clinicopathological Features, Triggers, Complement Abnormalities, Treatment, and Outcomes of C3 Glomerulopathy

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Ravindran, Aishwarya, Mayo Clinic, Rochester, Minnesota, United States
  • Fervenza, Fernando C., Mayo Clinic, Rochester, Minnesota, United States
  • Sethi, Sanjeev, Mayo Clinic, Rochester, Minnesota, United States
Background

C3 glomerulopathy (C3G), comprising C3 glomerulonephritis (C3GN) and dense deposit disease (DDD), is characterized by glomerular accumulation of complement proteins due to over activation of the alternative pathway of complement. Most of the reports on C3G are based on individual cases or small series of C3GN/DDD patients.

Methods

We provide a comprehensive evaluation of 114 patients seen at Mayo Clinic during a 10-year period (2007-2016), of which 102 (89.5%) had C3GN and 12 (10.5%) had DDD.

Results

The median age at diagnosis of C3G was 42 years; C3GN patients were older (median age 42 years) while DDD patients were younger (median age 23.5 years). The median serum creatinine and proteinuria at presentation was 1.6 mg/dL and 2605 mg/24 hours. Hematuria was present in 100 (87.7%) patients. C3 levels were low in only 44.6% patients. Monoclonal gammopathy was present in 37.9% patients; 65.1% of the patient’s ≥ 50 years had a monoclonal Ig. 28.9% patients had a history of infection and 23.7% patients had an associated autoimmune abnormality. Mutations in complement regulating proteins including CFH, C3 nephritic factor, and other autoantibodies (anti-CFH and CFB) were detected in 43.9%, 43.9% and 10.9% patients, respectively. All patients tested carried C3G risk-associated polymorphisms, the most common being CFH allele variants. Membrano- and mesangial proliferative glomerulonephritis were most common patterns of injury on kidney biopsy. Most patients received steroids and other immunosuppressive drugs. After a median follow-up of 34.6 months, the median serum creatinine was 1.4 mg/dL and the median proteinuria was 809 mg/24 hours. Eighteen patients (15.8%) progressed to ESRD. The predictors of ESRD on univariate analysis were serum creatinine >1.5 mg/dL, proteinuria >3 g/24 hours at diagnosis, severity of global glomerulosclerosis and the extent of tubular atrophy and interstitial fibrosis.

Conclusion

C3G is a heterogeneous disease entity that affects both children and adults. In younger patients, both mutations and autoantibodies to complement regulating proteins are present, while in older patients, a monoclonal Ig, which presumably acts as an autoantibody to complement regulating proteins, is most frequently identified.