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Abstract: FR-PO898

Clinical Value of Complement Biomarkers in Autoimmune Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1203 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Khalili, Myriam, Hopital du Sacre-Coeur de Montreal, Town of Mount Royal, Quebec, Canada
  • Bonnefoy, Arnaud, CHU Ste-Justine - Université de Montréal, Montréal, Quebec, Canada
  • Quadri, Jérémy, CHU Ste-Justine, Montréal, Quebec, Canada
  • Rioux, Jean-Philippe, Hopital du Sacre-Coeur de Montreal, Town of Mount Royal, Quebec, Canada
  • Troyanov, Stephan, Hopital du Sacre-Coeur de Montreal, Town of Mount Royal, Quebec, Canada
Background

Complement activation plays a central role in the mechanisms of injury of autoimmune glomerular diseases. Urinary excretion of different complement biomarkers could indicate relevant activated pathogenic pathways (classical, lectin, alternate), parallel disease activity and add clinical value beyond proteinuria.

Methods

We performed a prospective observational cohort study of 81 patients including focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), lupus nephritis (LN) and ANCA-associated vasculitis (AAV). Urinary samples were collected at different time points. We measured proteinuria, C4a (classical and lectin pathway), Bb (alternative pathway), and sC5b-9 (terminal cascade), expressed as creatinine ratios. We assessed remission status (partial or complete) as currently defined for each disease. For AAV, we assessed the renal BVAS score after 6 months of treatment.

Results

At baseline, urinary excretion of sC5b-9 was present in each individual (4.28, IQR 0.84-21.96 µg/mmol creatinine) and correlated with the initial proteinuria (p<0.05 for each disease). Urinary C4a and Bb were mostly absent. In those who obtained clinical remission, we observed a 92% reduction in urinary sC5b-9 levels, which was greater than the 69% reduction observed in proteinuria (p=0.02 by Wilcoxon signed-rank test), suggesting earlier and more precise variations in urinary sC5b-9. This same pattern occurred with each disease group (table), and reached statistical significance for MN (p=0.05) and AAV (p=0.03). When no clinical remission was obtained, there was a greater increase in sC5b-9 levels (43%) than for proteinuria (21%), although not statistically significant (n=12, p=0.68).

Conclusion

In active autoimmune glomerular diseases, urinary sC5b-9 is measurable in all individuals. In those who obtained a clinical remission, the urinary sC5b-9 reduction was greater than the decline observed with proteinuria. This pattern was seen in each disease suggesting that C5b9 is a more sensitive marker of remission.

 ninitial urinary sC5b-9*
(µg/mmol creatinine)
initial proteinuria*
(g/mmol creatinine)
% RemissionReduction of proteinuria at remission (%)*Reduction of urinary sC5b-9 at remission (%)*
FSGS165.360.465676.286.5
IgAN191.180.146260.378.9
LN165.800.3310071.493.0
MN1422.930.677079.895.1
AAV160.800.0910068.489.3

* median

Funding

  • Government Support - Non-U.S.