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Abstract: SA-OR64

Overlapping Pathologic Findings in the Kidney Allograft Biopsy: Pitfalls for the Molecular Microscope Diagnostics System (MMDx)

Session Information

Category: Transplantation

  • 2102 Transplantation: Clinical

Authors

  • Schachtner, Thomas, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Weidmann, Lukas, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Harmacek, Dusan, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Korach, Raphael, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Bortel, Nicola, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • López, Kai Castrezana, UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
  • Mueller, Thomas F., UniversitatsSpital Zurich, Zurich, Zürich, Switzerland
Background

The Molecular Microscope Diagnostic System (MMDx) has been suggested to add diagnostic value in cases suspicious of antibody-mediated (ABMR) and T cell-mediated rejection (TCMR). Other overlapping pathologies, however, have the potential to mimic molecular rejection.

Methods

In this single-center cohort of 326 indication kidney transplant biopsies assessed by histology and MMDx at the University Hospital Zurich, we analyzed 66 cases with overlapping pathologic findings by histology: 15 cases with pyelonephritis, 21 cases with BK nephropathy (BKVN), 5 cases with acute interstitial nephritis (AIN), and 28 cases with recurrent/de novo glomerulonephritis (GN).

Results

Pyelonephritis: 5 of 15 cases (33%) with pyelonephritis showed minor molecular findings (normal rejection score but abnormal ABMR and/or TCMR score or vice versa), which were diagnosed in only 18 of 260 (7%) cases without overlapping pathologies (p=0.004). 8 of 15 cases (53%) with pyelonephritis showed a TCMR phenotype score (R2) ≥0.10. BKVN: 4 of 21 cases (19%) with BKVN showed minor molecular findings, whereas 3 (14%), 3 (14%), and 6 (29%) of 21 cases showed ABMR, TCMR, and ABMR/TCMR, respectively. 11/21 cases (52%) with BKVN showed an all ABMR rejection phenotype score (sum of R4, R5, and R6) ≥0.20, none of which had proven ABMR by histology. AIN: 3 of 5 cases (60%) with AIN showed molecular TCMR, of which 2 cases showed mixed ABMR/TCMR in the absence of any antibody-mediated changes by histology. GN: 21 of 28 cases (75%) with GN showed no molecular ABMR/TCMR, whereas 2 of 28 cases (7%) showed minor molecular findings, and 5 of 28 cases (18%) showed ABMR. Surprisingly, 16 of 28 cases (57%) showed an all ABMR rejection phenotype score ≥0.20, and 8 of 28 cases (29%) showed a late-stage ABMR score ≥0.20.

Conclusion

Minor molecular findings should always suggest the presence of any overlapping pathology. Cases of pyelonephritis, BKVN, and AIN mostly mimic molecular rejection and might be misleading in their interpretation. Although GN does not show molecular rejection in most cases, the elevated ABMR scores suggest a GN-associated phenomenon.

Funding

  • Private Foundation Support