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Abstract: FR-PO457

Clinical Value of Urinary C5b-9 Complement Complex in Overt Diabetic Nephropathy

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Pelletier, Karyne, Hôpital Sacré-Coeur de Montréal, Montreal, Quebec, Canada
  • Bonnefoy, Arnaud, CHU Sainte-Justine, Montréal, France
  • Chapdelaine, Hugo, Institut de Recherches Cliniques de Montréal, Montreal, Quebec, Canada
  • Lejars, Matthieu, CHU Sainte-Justine, Montréal, France
  • Pichette, Vincent, Université de Montréal, Montreal, Quebec, Canada
  • Madore, Francois, Hôpital Sacré-Coeur de Montréal, Montreal, Quebec, Canada
  • Brachemi, Soumeya, Service de néphrologie, CHUM, Montreal, Quebec, Canada
  • Troyanov, Stephan, Hôpital Sacré-Coeur de Montréal, Montreal, Quebec, Canada
Background

Experimental studies support a role of complement activation through the lectin pathway in diabetic nephropathy (DN). We evaluated urinary levels of C5b-9 membrane attack complex (MAC) in patients with overt DN, tested associations with eGFR decline, proteinuria and inflammatory biomarkers.

Methods

This is a prospective observational cohort study of patients with overt DN followed for 2.1 years (1.6-2.8) from hospitals affiliated with the University of Montreal. We obtained repeated measurements of proteinuria, urinary MAC and inflammatory biomarkers expressed as urinary creatinine ratios. We also compare levels to patients with MGN, FSGS, AAV and IgAN.

Results

The diabetic cohort (n=83) was 80% male. The initial eGFR was 25 ± 9 mL/min/1.73m2 with an eGFR decline of 2.9 ± 3.0 mL/min/1.73m2/year. The median MAC-to-creatinine ratio was 1.89 (0.48-10.37) mg/mmol. The highest quartile was associated with a rate of decline in renal function of -5.1 ±mL/min/1.73m2/year compared to -2.2 ± 2.6 (p < 0.001) (Figure 1). Urinary C5b-9 was also associated with inflammatory biomarkers and with the proteinuria (Spearman's rho 0.80, p<0.001). Furthermore, at comparable levels of proteinuria, the patients with DN in this study had similar or higher levels of urinary MAC than patients with other immunologic glomerulonephritis (n=62).

Conclusion

Complement MAC is present in the urine of patients with overt DN and higher levels correlate with a more rapid rate of renal function decline. At similar proteinurias, patients with DN had similar or higher levels compared to those with MGN, FSGS, AAV and IgAN. These findings support that urinary C5b-9 excretion in DN is not solely caused by a passive filtration of plasma C5b-9, but is locally expressed and implicated in the pathogenesis of DN.

Figure 1. Rate of renal function decline according to urinary C5b-9 quartiles

Funding

  • Government Support - Non-U.S.