Abstract: FR-PO726

C3G-Associated with Monoclonal Gammopathy

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

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

Monoclonal immunoglobulins (MIg) may act a functional inhibitor of the alternate complement pathway thereby playing a causal role in the pathogenesis of C3 glomerulopathy (C3G). In this study, we describe the clinicopathological features, hematological evaluation, treatment and outcomes of C3G associated with MIg.

Methods

We identified 95 patients seen at the Mayo Clinic from 2007-2016 with a diagnosis of C3 glomerulopathy (C3GN or DDD) who were tested for a monoclonal protein.

Results

36 (37.9%) patients were positive for MIg; 65.1% of patient ≥50 years were positive (17 times higher than the expected rate). The median age at diagnosis was 60 years (range: 20-85), 25 males and 11 females. The median serum creatinine and proteinuria was 1.9 mg/dL and 3000 mg/24 hours. Hematuria was present in 28 (93.3%) patients. Twelve (34.3%) patients had low C3 and 4 (11.4%) had low C4. Twenty-six (72.2%) patients were classified as MGUS/MGRS, 5 (13.9%) multiple myeloma, 2 (5.6%) smoldering myeloma, 1 (2.8%) CLL, 2 with cryoglobulins (5.6%) 1 of which was type I cryoglobulin and the other was associated with lymphoma of the stomach. The most common abnormality was the presence of C3 nephritic factor in 10 (43.5%) patients and autoantibodies to complement factor H or B in 3 patients (13%). Six (30%) patients had mutations in complement regulating proteins. Of the 36 patients, 33 (91.7%) received steroids and/or other immunosuppressive drugs. At a median follow-up of 43.5 months, the median serum creatinine and proteinuria was 1.4 mg/dL and 749 mg/24 hours. Nine (25%) patients progressed to end stage renal disease. Sixteen (44.4%) received targeted therapy for MIg. Of these 11 (68.8%) patients achieved stable renal function, while the remaining 5 (31.2%) progressed to ESRD, of which 3 (18.7%) had multiple myeloma and only 2 (12.5%) had MGUS/MGRS. With regards to non-targeted treatment for the MGUS/MGRS group, 4 (20%) patients progressed to ESRD.

Conclusion

Our study shows a high prevalence of MIg in C3G patients. C3 nephritic and autoantibodies were more common compared to mutations suggesting that the MIg likely acts as an autoantibody to complement regulating proteins. Targeted treatment of MIg, in particular with MGUS/MGRS, resulted in stabilization of renal function in a majority of the patients.