Kidney Week

Abstract: TH-PO614

Clinical Significance of Immune Deposits and Complement System Activation in Patients with FSGS: Findings from the CureGN Study

Session Information

• Membranous Nephropathy, FSGS, and Minimal Change Disease
  October 24, 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

• Caliskan, Yasar, Saint Louis University, St Louis, Missouri, United States

Yasar Caliskan, MD

• Royal, Virginie, Division of Pathology, Hôpital Maisonneuve-Rosemont, University of Montreal, Montreal, Quebec, Canada

Virginie Royal, MD

• Troyanov, Stephan, Division of Nephrology, Hôpital du Sacré-Cœur-de-Montréal, University of Montreal, Montreal, Quebec, Canada

Stephan Troyanov, MD

• Bonnefoy, Arnaud, Division of Hematology, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada

Arnaud Bonnefoy, PhD

• Merlen, Clémence, Division of Hematology, Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada

Clémence Merlen, PhD

• Schnitzler, Mark, Saint Louis University, St Louis, Missouri, United States

Mark Schnitzler, PhD

• Edwards, John C., Saint Louis University, St Louis, Missouri, United States

John C. Edwards, MD, PhD

• Lentine, Krista L., Saint Louis University, St Louis, Missouri, United States

Krista L. Lentine, MD, PhD, FASN

• Laurin, Louis-Philippe, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada

Louis-Philippe Laurin, MD, MS, MSc

Background

Glomerular IgM and C3 deposits are commonly found in FSGS and assumed to be the result of passive trapping rather than immune mechanisms. The clinical significance of IgM and C3 immunostaining, and their association with complement system activation have not been elucidated yet. We sought to assess the value of immunofluorescence (IF) findings and urinary complement fragments in defining disease activity and progression.

Methods

FSGS patients with available pathology assessment from the CureGN cohort were reviewed and we tested associations of glomerular Igs and C3 staining intensity by IF with the urinary membrane attack complex (sC5b9), proteinuria and time to a composite outcome, defined by kidney failure or 40% eGFR decline. We compared urinary levels of sC5b9 expressed as creatinine and protein ratios.

Results

We analyzed 175 FSGS patients, including 63(36%) incident subjects enrolled within 6 months of pathology review. Glomerular IgM, C3 and IgG deposits were found in 88(50%), 48(27.4%) and 27(15.4%) patients, respectively. 44(91%) and 20(48%) of patients with C3 deposition presented with accompanying IgM and IgG deposition, respectively. C3 deposition was correlated with global sclerosis (r=0.27,p<0.001), interstitial fibrosis and tubular atrophy (IFTA) (r=0.17,p=0.028). In incident patients, urinary sC5b9 levels correlated with total segmental sclerosis (r=0.35,p=0.006) and IFTA (r=0.35,p=0.007). There was no correlation between urinary sC5b9 and the intensity of C3, IgM and IgG staining. IFTA and urinary sC5b9 level at enrollment were independent risk factors for composite outcome (HR 1.92, 95%CI 1.45-2.53,p<0.001 and HR 2.15, 95%CI 1.39-3.33,p<0.001, respectively).(Fig. 1)

Conclusion

In patients with FSGS, a higher urinary level of sC5b9 appears to be associated with eGFR loss independently of proteinuria level. Glomerular C3 deposition was associated with fibrotic lesions which was a predictor of disease progression.