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Abstract: SA-PO957

Utility of Anti-PLA2R and Anti-THSD7A Antibodies in Predicting Membranous Nephropathy Recurrence: A Multi-Center Retrospective Cohort Study

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Hullekes, Frank E., Massachusetts General Hospital, Boston, Massachusetts, United States
  • Verhoeff, Rucháma, Massachusetts General Hospital, Boston, Massachusetts, United States
  • Cravedi, Paolo, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Riella, Leonardo V., Massachusetts General Hospital, Boston, Massachusetts, United States
Background

Membranous nephropathy (MN) is a leading cause of nephrotic syndrome, frequently leading to kidney failure. The discovery of autoantibodies against podocyte antigens, including PLA2R and THSD7A, is a major advancement in our understanding of disease pathophysiology. The predictive value of PLA2R and THSD7A serum Abs in detecting recurrent MN remains undefined.

Methods

Through the Post-Transplant Glomerular Disease (TANGO) Consortium, we initiated a multi-center retrospective cohort study, investigating MN post-Tx, using clinical data and serum samples. Adults with biopsy-proven MN, transplanted between 2005-2021, were identified to study the predictive value of PLA2R and THSD7A in detecting recurrence.

Results

22,921 patients were screened by 16 Tx centers across 3 continents. 86 kidney Tx recipients with biopsy-proven MN were included for anti-PLA2R Abs assessment. 46 patients were also screened for anti-THSD7A Abs. 37 patients (43%) developed recurrence at a median of 3.5 years (IQR: 1.5-6.1). Of these, 22 (59%) tested positive for anti-PLA2R Abs prior to recurrence. All 46 patients tested negative for anti-THSD7A Abs. The mean anti-PLA2R Abs for samples collected prior to recurrence was 136.9 RU/mL (95 CI: 55.7-218.2). These were taken with a median of 2.7 months (IQR: 12.9 – 0.1) before recurrence. Patients with recurrence had higher anti-PLA2R Ab than patients without (Figure 1A). Therapy consisted of RAAS inhibition for 30 patients (81%) and/or rituximab in 21 (56%) of the cases. After treatment, anti-PLA2R Abs notably decreased, with a mean of 13.9 RU/mL (95 CI: 3.7-24.1). These were taken with a median of 25.1 months (IQR: 4.0 – 54.6) after recurrence (Figure 1B).

Conclusion

The presence of anti-PLA2R antibodies may have predictive value in detecting recurrent MN post-transplant. Monitoring anti-PLA2R antibody levels and implementing appropriate therapies, in particular rituximab, could potentially aid in the management of recurrent MN.