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Abstract: SA-PO423

Biomarkers of Complement Activity in C3 Glomerulopathy Patients

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Bomback, Andrew S., Columbia University, New York, New York, United States
  • Kil, Byum hee, Columbia University, New York, New York, United States
  • Luu, Amanda, Achillion Pharmaceuticals, New Haven, Connecticut, United States
  • Zhao, Yongsen, Achillion Pharmaceuticals, Inc., New Haven, Connecticut, United States
  • Galvan, Manuel D., Achillion Pharmaceuticals, New Haven, Connecticut, United States
  • Thanassi, Jane A., Achillion Pharmaceuticals, New Haven, Connecticut, United States
  • Kocinsky, Hetal S., Achillion Pharmaceuticals, New Haven, Connecticut, United States
  • Podos, Steven D., Achillion Pharmaceutical, Inc., New Haven, Connecticut, United States
  • Yang, Wengang, Achillion Pharmaceuticals, New Haven, Connecticut, United States
  • Huang, Mingjun, Achillion Pharmacueticals, New Haven, Connecticut, United States
  • Appel, Gerald B., Columbia University College of Physicians and Surgeons, Scarsdale, New York, United States
Background

C3 glomerulopathies (C3G) are characterized by isolated or dominant glomerular C3 staining on immunofluorescence that implies an etiology rooted in dysregulation of the alternative complement pathway. To date, no biomarkers for disease activity have reliably predicted outcomes in C3G.

Methods

We measured circulating factor D, factor B, Ba, Bb, plasma and serum C3, and C3a as potential biomarkers of complement activity in a group of C3G patients with longitudinal outcome data. The primary outcome combined doubling of creatinine, progression to CKD stage 5, ESRD, transplantation, or death. The secondary outcome was remission, defined as stable creatinine with >50% reduction in proteinuria to subnephrotic range.

Results

We compiled a biomarker profile on 38 C3G patients (25 with C3 glomerulonephritis and 13 with dense deposit disease) with a mean follow-up of 62 months from diagnosis to last encounter. Factor D levels were low in 50% of patients, factor B levels were low in 21% of patients, plasma C3 levels were low in 53% of patients, and serum C3 levels were low in 42%. Factor B split products, Ba and Bb, were elevated in 66% and 55% of patients, respectively, while C3a was elevated in 61% of patients. Seven patients reached late or end stage kidney disease. In univariate analyses, Ba (p=0.002) and Bb (p=0.03) levels, but not C3a levels (p=0.2), emerged as predictors for the primary outcome. Plasma (p=0.04) but not serum (p=0.2) levels of C3 were also predictive of progression. Seventeen patients achieved disease remission, but no biomarker was predictive of this outcome.

Conclusion

Elevated levels of the factor B split products (Ba and Bb), which denote newly formed C3 convertase of the alternative pathway, are associated with progression of C3G to advanced and end stage kidney disease. These biomarkers may help risk-stratify newly diagnosed C3G patients and present a treatment target for disease.

Funding

  • Commercial Support