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Kidney Week

Abstract: SA-PO355

Complement Deposits Are Not Just Non-Specifically Entrapped in FSGS: C4d Can Precede the Development of Recurrent FSGS in Allograft Biopsies

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Van de Lest, Nina A., Leiden University Medical Center, Leiden, Netherlands
  • Zandbergen, Malu, Leiden University Medical Center, Leiden, Netherlands
  • Wolterbeek, Ron, Leiden University Medical Center, Leiden, Netherlands
  • Bruijn, Jan A., Leiden University Medical Center, Leiden, Netherlands
  • Bajema, Ingeborg M., Leiden University Medical Center, Leiden, Netherlands
  • Scharpfenecker, Marion, Leiden University Medical Center, Leiden, Netherlands
  • Chua, Jamie S., Leiden University Medical Center, Leiden, Netherlands
Background

Complement deposition in focal segmental glomerulosclerosis (FSGS) is often considered aspecific entrapment in sclerotic lesions. However, recent studies showed that complement activation may be involved in the development of FSGS. We previously found that C4d deposition precedes the development of segmental glomerulosclerosis in an animal model of FSGS, and that C4d is present in non-sclerotic glomeruli of patients with FSGS. Here, we investigated if complement activation can precede the development of recurrent FSGS after transplantation. To this end, we studied C4d deposition in transplantation biopsies prior to the development of recurrent FSGS lesions.

Methods

We stained allograft biopsies without FSGS lesions from 34 patients with native primary FSGS for C4d: 18 patients developed recurrent proteinuria or recurrent FSGS in follow-up biopsies and 16 patients did not. As controls, we included allograft biopsies from 34 patients with a native kidney disease other than FSGS. Patients with confounding factors for C4d deposition were excluded.

Results

In allograft biopsies of patients with recurrent proteinuria or recurrent FSGS, glomerular C4d preceded the recurrence of FSGS lesions in 72% of patients (n=18). This was significantly more prevalent than in transplantation controls (27%; p=0.001). In 16 patients who did not develop recurrent proteinuria or FSGS, the prevalence of glomerular C4d was similar compared to transplantation controls (50% and 27%, respectively; p<0.10).

Conclusion

Our data show that C4d deposition precedes the recurrence of segmental lesions in patients with native FSGS, specifically at the onset of proteinuria. As the FSGS lesions had not yet developed, our data refute the hypothesis of non-specific entrapment as sole etiology for observed complement deposition. As C4d is a stable biomarker of complement activation, our data provide further evidence for complement activation in the development of FSGS. We suggest that a subgroup of patients with FSGS may have increased susceptibility to complement-mediated injury. Complement-inhibiting therapies could be promising in these cases.