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Abstract: SA-PO1053

Donor-Derived Cell-Free DNA in Biopsy-Proven Antibody-Mediated Rejection (ABMR) vs. Recurrent IgA Nephropathy After Kidney Transplantation

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Osmanodja, Bilgin, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Akifova, Aylin, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
  • Budde, Klemens, Charite Universitatsmedizin Berlin, Berlin, Berlin, Germany
Background

Antibody-mediated rejection (ABMR) and recurrent IgA nephropathy (IgAN) are major causes of graft loss and show comparable clinical features such as decline in renal function, proteinuria or worsening hypertension. Since ABMR and recurrent IgAN are indistinguishable using eGFR and urine albumin-creatinine-ratio (uACR) alone, we evaluated the ability of donor-derived cell-free DNA (dd-cfDNA) to discriminate both entities in consecutive cases from an ongoing prospective, observational trial.

Methods

At the time of clinically indicated biopsies, we collected venous blood samples and measured absolute (cp/mL) and relative (%) dd-cfDNA. We included 57 dd-cfDNA-matched biopsies, and assigned them to 3 groups based on histopathology: (1) active or chronic active ABMR (n=21), (2) recurrent IgAN (n=15), (3) no signs of rejection, infection or glomerulonephritis (n=21).

Results

Absolute and relative dd-cfDNA were lower in recurrent IgAN than in ABMR (median 11 cp/mL [IQR 7 - 13] vs. 76 cp/mL [IQR 57 - 103], p<0.001; median 0.32% [IQR 0.24 - 0.41] vs. 1.68% [IQR 1.1 - 2.7], p<0.001), but did not differ between recurrent IgAN and no rejection (median 11 cp/mL [IQR 7 - 13] vs. 12 cp/mL [IQR 7 - 16], p=0.995; median 0.32 % [IQR 0.24 - 0.41] vs. 0.30 % [IQR 0.26 - 0.54], p=0.983) (Figure 1). Using the prespecified cutoff of 50 cp/mL, no patient with recurrent IgAN, but 17/21 patients (81%) with ABMR had increased absolute dd-cfDNA levels. Four patients (27%) with crescent formation as a sign of severe recurrent IgAN had low absolute (min-max: 6 - 21 cp/mL) and relative dd-cfDNA (min-max 0.26 - 0.35%) as well.

Conclusion

Dd-cfDNA does not increase in recurrent IgAN after kidney transplantation.

Figure 1. Dot plots showing biopsy-matched measurements of (A) absolute dd-cfDNA (B) relative dd-cfDNA (C) eGFR and (D) uACR in KTR with ABMR, no rejection, and recurrent IgAN.

Funding

  • Commercial Support – Oncocyte