Kidney Week

Abstract: FR-OR58

Immunodeposits and Urinary Complement Activation Fragments Are Linked to IgAN Activity and Progression: Findings from the CureGN Study

Session Information

• IgA Nephropathy: New Therapies and Insights
  October 25, 2024 | Location: Room 6D, Convention Center
  Abstract Time: 05:00 PM - 05:10 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

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

Virginie Royal, MD

• Caliskan, Yasar, SSM Health Saint Louis University Hospital, Saint-Louis, Missouri, United States

Yasar Caliskan, MD

• Lentine, Krista L., SSM Health Saint Louis University Hospital, Saint-Louis, Missouri, United States

Krista L. Lentine, MD, PhD, FASN

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

Arnaud Bonnefoy, PhD

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

Clémence Merlen, PhD

• Schnitzler, Mark, SSM Health Saint Louis University Hospital, Saint-Louis, Missouri, United States

Mark Schnitzler, PhD

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

Louis-Philippe Laurin, MD, MS, MSc

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

Stephan Troyanov, MD

Background

Small cohorts have reported variable associations between immunodeposits and complement activation with clinical outcomes in IgA nephropathy (IgAN). In parallel, therapeutic trials show encouraging results using complement inhibition. We sought to confirm the value of immunofluorescence findings and urinary complement fragments in defining disease activity and progression.

Methods

Using IgAN patients with available pathology assessment from the CureGN cohort, we tested associations between immunoglobulins and C3 distribution and intensity by immunofluorescence with the Oxford MEST-C score, urinary membrane attack complex (sC5b9), proteinuria, and survival from a combined outcome; kidney failure or 40% decline in eGFR.

Results

We analyzed 247 IgAN patients, including 115 incident subjects enrolled within 6 months of kidney biopsy. IgA and C3 staining intensity were associated with mesangial hypercellularity. Localization of IgM, C3, and IgA deposits along capillaries was associated with endocapillary hypercellularity, cellular crescents, and foot process effacement. In incident subjects, urinary sC5b9 showed associations with global endocapillary hypercellularity, crescent formation, and IgM and C3 deposition along capillaries. While immunodeposits were not associated with a combined outcome, urinary sC5b9 was. When adjusting for the level of proteinuria, significant interaction existed (p=0.009), indicating elevated urinary sC5b9 correlated with a reduced outcome in those with elevated proteinuria (illustrated by Kaplan Meier curves using dichotomizing urinary measurements).

Conclusion

In IgAN, intensity and localization of immunodeposits correlate with mesangial, endocapillary, and extracapillary hypercellularity and the level of urinary sC5b9. In turn, the urinary sC5b9 is independently associated with eGFR loss.