Abstract: FR-PO700

C4d Deposits in FSGS before the Development of Sclerosis

Session Information

Category: Glomerular

  • 1002 Glomerular: Basic/Experimental Pathology

Authors

  • van de Lest, Nina A., Leiden University Medical Center, Dept.Pathology, Leiden, Netherlands
  • Zandbergen, Malu, Leiden University Medical Center, Dept.Pathology, Leiden, Netherlands
  • Kreutz, Reinhold, Charite-University Medicine Berlin, Berlin, Germany
  • Bruijn, Jan A., Leiden University Medical Center, Dept.Pathology, Leiden, Netherlands
  • Bajema, Ingeborg M., Leiden University Medical Center, Dept.Pathology, Leiden, Netherlands
  • Scharpfenecker, Marion, Leiden University Medical Center, Dept.Pathology, Leiden, Netherlands
  • Chua, Jamie S., Leiden University Medical Center, Dept.Pathology, Leiden, Netherlands
Background

Immune deposits of complement components are occasionally seen in patients with FSGS. These deposits are non-diagnostic and are often considered as nonspecific entrapment in sclerotic lesions. However, deposits of IgM and C3 have also been observed in non-sclerotic glomeruli. Moreover, recent animal studies demonstrated a role for the complement system in the pathogenesis of FSGS. Here, we investigated the pattern of complement deposition in glomeruli of experimental and human FSGS, using the complement activation biomarker C4d.

Methods

Kidney sections of Munich Wistar Frömter (MWF) rats of 4 (no proteinuria), 8 (only proteinuria) and 24 (proteinuria with glomerulosclerosis) weeks of age were stained for C4d. Age-matched spontaneously hypertensive rats (SHR) with no proteinuria were used as controls. Also, we performed a C4d staining on 40 kidney biopsies of patients with FSGS and 46 control biopsies of patients with minimal change disease (MCD) who have proteinuria without segmental glomerulosclerosis. Prevalence and localisation of C4d deposition in glomeruli were investigated.

Results

The percentage of C4d positive glomeruli was significantly higher in MWF rats at 8 and 24 weeks of age compared to controls (p<0.001 and p<0.01 respectively). C4d deposits were also more frequently observed in rats of 4 weeks of age, yet not significant. At 24 weeks, 94% of sclerotic glomeruli were C4d positive, whereas 50% of C4d positive glomeruli showed segmental glomerulosclerosis. In human biopsies, glomerular C4d deposits were observed in 75% of FSGS and 35% of MCD cases (p<0.001). Of positive cases, 40% of glomeruli were positive in FSGS compared to 33% in MCD. In FSGS, C4d was co-localized with segmental sclerosis in 57% and was present in non-sclerotic glomeruli or non-sclerotic parts of sclerotic glomeruli in 45%.

Conclusion

Here, we show that in the MWF rat model for FSGS, C4d deposits are present before the development of glomerulosclerosis. Similarly, C4d deposits were present in non-sclerotic glomeruli of patients with FSGS and in patients with MCD who have proteinuria without segmental glomerulosclerosis. These results indicate that C4d deposition could be involved in the development of FSGS.