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Abstract: TH-PO789

Pre-Transplant Nephrin Autoantibodies Predict Post-Transplant Recurrent Focal Segmental Glomerulosclerosis (FSGS)

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Weins, Astrid, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Hamroun, Aghiles, Centre Hospitalier Universitaire de Lille, Lille, Hauts-de-France, France
  • Provot, Francois, Centre Hospitalier Universitaire de Lille, Lille, Hauts-de-France, France
  • Keller, Keith H., Broad Institute, Cambridge, Massachusetts, United States
  • Gibier, Jean-Baptiste, Centre Hospitalier Universitaire de Lille, Lille, Hauts-de-France, France
  • Watts, Andrew James baxter, Brigham and Women's Hospital, Boston, Massachusetts, United States
Background

Recurrent Focal Segmental Glomerulosclerosis (FSGS) following renal transplant occurs commonly and can lead to early graft failure. Evidence supports a recipient derived circulating factor(s) that leads to early post-transplant recurrence however its identity has remained elusive. The recent discovery of nephrin autoantibodies in minimal change disease (MCD) lead us to hypothesize that nephrin autoantibodies pre-transplant may predict early recurrence in FSGS.

Methods

Single center retrospective study of 16 consecutive patients undergoing renal transplant for biopsy proven primary podocytopathy from the Centre Hospitalier Regional Universitaire de Lille between 2012 and 2019. Circulating anti-nephrin antibodies were evaluated pre-transplant by indirect ELISA. Recurrent FSGS was diagnosed on biopsy and the presence of nephrin antibodies was evaluated by immunofluorescence (IF).

Results

The median age of disease onset and transplant were 19 years (IQR 8.5-31.25) and 31 years (IQR 23.5-43.75) respectively. Disease recurrence was seen in half of the patients and occurred early, within 1 day, in 62.5% (n=5/8). One quarter (n=4/16) of the patients were serologically positive for nephrin autoantibodies at the time of transplant (Fig 1) and as expected, this was universally associated with disease recurrence (n=4/4) and constituted the majority, 80% (n=4/5) of those with early recurrence. There was complete concordance with anti-nephrin antibodies in the renal biopsies. Approximately one third (n=5/16) of the patients underwent pre-transplant plasma exchange (PE) and the majority (n=4/5) were serologically negative for nephrin autoantibodies. Post-transplant recurrence occurred in 2 of 5 patients and one of them was anti-nephrin antibody positive despite pre-emptive PE.

Conclusion

The presence of circulating nephrin autoantibodies at the time of transplant was universally associated with post- transplant early recurrence and were identified within the kidney disease. Our findings support an important role for nephrin autoantibodies in the pathogenesis of recurrent FSGS. In those patients undergoing pre-emptive PE this is would be an important biomarker to guide treatment as one patient who recurred despite PE has persistent circulating nephrin autoantibodies.

Funding

  • Private Foundation Support