Additional Diagnoses Other Than Rejection in the Kidney Allograft Biopsy: Pitfalls for Biopsy-based Transcript Diagnostics.

Abstract

Background: Biopsy-based transcripts associated with antibody-mediated rejection (AMR) hold promise as substitutes for C4d positivity. However, their utility in cases with additional diagnoses other than rejection remains inadequately studied.

Methods: In our comprehensive analysis of 326 kidney allograft biopsies, assessed by histology and the Molecular Microscope Diagnostic System, we identified 68 cases characterized by additional pathologies, including pyelonephritis (n = 15), BK nephropathy (n = 20), acute interstitial nephritis (n = 5), and glomerular diseases (n = 28).

Results: Among cases with pyelonephritis, 7 of 15 cases (46%) showed a rejection-like signal, 4 above (16%) and 3 (20%) below diagnostic thresholds. Notably, the T cell-mediated rejection (TCMR) archetype score R2 (median, 0.13; interquartile range [IQR], 0.04-0.34) predominantly contributed to this observation. In BK nephropathy, 13 of 20 cases (65%) showed a rejection-like signal, 10 (50%) above and 3 (15%) below diagnostic thresholds. Elevated TCMR R2 (median, 0.07; IQR, 0.00-0.41) and all AMR archetype scores R4-6 (median, 0.23; IQR, 0.07-0.53) were driving factors. Among cases with acute interstitial nephritis, 3 of 5 cases (60%) showed TCMR-like signal with elevated R2 scores (median, 0.13; IQR, 0.00-0.54). Conversely, only 5 of 28 cases (18%) showed a rejection-like signal in glomerular disease cases, whereas 57% displayed all AMR archetype scores of ≥0.30.

Conclusions: Additional pathologies can affect the Molecular Microscope Diagnostic System output, giving a molecular rejection-like signal. The prevalence of rejection-like signals below diagnostic thresholds is noteworthy, warranting caution and prompting further investigation.