Kidney Week

Abstract: SA-PO793

Correlations in Histology and Complement Biomarkers in C3 Glomerulopathy

Session Information

• C3G, TMA, MGRS, Amyloidosis, and More
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Hall, Jillian R., University of Iowa Health Care, Iowa City, Iowa, United States

Jillian R. Hall

• Hall, Monica D., University of Iowa Health Care, Iowa City, Iowa, United States

Monica D. Hall, RN

• Fergus, Lauren O., University of Iowa Health Care, Iowa City, Iowa, United States

Lauren O. Fergus

• Walker, Patrick D., University of Iowa Health Care, Iowa City, Iowa, United States

Patrick D. Walker, MD, FASN

• Zhang, Yuzhou, University of Iowa Health Care, Iowa City, Iowa, United States

Yuzhou Zhang, PhD

• Smith, Richard J., University of Iowa Health Care, Iowa City, Iowa, United States

Richard J. Smith, MD

• Nester, Carla M., University of Iowa Health Care, Iowa City, Iowa, United States

Carla M. Nester, MD, MS, FASN

Group or Team Name

• Molecular Otolaryngology and Renal Research Laboratories.

Background

C3 Glomerulopathy (C3G) is characterized by complement dysregulation and C3 deposition in glomeruli. We reviewed characteristics of baseline kidney biopsies to determine whether features of activity and/or chronicity correlate with clinical parameters and/or complement biomarkers at presentation.

Methods

Data from the University of Iowa’s C3G Natural History Study were used. Criteria for entry included baseline native biopsy diagnosis of C3G and complement biomarkers within 1 year of biopsy. Patients with a history of dialysis, transplant, or anti-complement therapy were excluded. Significance was assessed using Pearson correlation coefficients with two-tailed p values (95% confidence) and one-way ANOVA analysis; p-values <0.05 were considered significant.

Results

57 of 104 subjects (54.8%) presented with an activity score of ≥9; 18 (17.3%) presented with a chronicity score of ≥4 (the a priori determinants of increased risk for progression to renal failure). Higher activity scores were associated with elevated C5Nefs (p = 0.012, R = 0.255) and soluble C5b-9 (p = 0.013, R = 0.259) levels. Higher chronicity scores were associated most strongly with an increase in Ba (p = 8.183e-10, R = 0.677) and a lower GFR (p = 1.665e-9, R = -0.558) and less strongly with increased C3 (p = 0.022, R = 0.265), C5 (p = 0.014, R = 0.331) and Bb (p = 0.037, R = 0.263) levels, and decreased C5Nefs (p = 0.012, R = -0.262 and soluble C5b-9 (p = 0.026, R = -0.232) levels.

Conclusion

The association of higher C5Nefs and soluble C5b-9 levels with increased activity scores is consistent with terminal pathway activity being a driver of inflammation, while the association of increased chronicity scores with a lower GFR and higher Ba reflects declining renal function independent of complement activity. While the increase in C3 and C5 and the decrease in soluble C5b-9 levels reflect decreased complement activity, Bb levels suggest some component of continued alternative pathway activity. In aggregate, these data support a role for complement biomarker testing in C3G.

Funding

• NIDDK Support