First Order Associations Between Banff Acute Lesions in Kidney Allograft Biopsies and a Urinary Cell Three-Gene Diagnostic Signature

Li, C.; Schwartz, J. E.; Salinas, T.; Dadhania, D. M.; DeVito, A.; Higgins, W.; Salvatore, S.; Seshan, S. V.; Muthukumar, T.; Suthanthiran, M.

doi:10.64898/2026.07.22.740171

bioRxiv · 10.64898/2026.07.22.740171

First Order Associations Between Banff Acute Lesions in Kidney Allograft Biopsies and a Urinary Cell Three-Gene Diagnostic Signature

Li, C.·Schwartz, J. E.·Salinas, T.·Dadhania, D. M.·DeVito, A.·Higgins, W.·Salvatore, S.·Seshan, S. V.·Muthukumar, T.·Suthanthiran, M.

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Abstract

Banff acute lesion scores underpin histologic classification of kidney allograft biopsies; however, biomarker studies rely on second-order associations with diagnostic categories that introduce confounding. We quantified the first-order relationships between Banff acute lesion scores and the validated urinary cell three-gene rejection signature. In 354 biopsy-urine pairs, three-gene signature scores computed using a locked regression equation incorporating absolute copy numbers of CD3E mRNA, CXCL10 mRNA, and 18S rRNA in urinary cell RNA-were related to glomerulitis (g), peritubular capillaritis (ptc), interstitial inflammation (i), and tubulitis (t). Signature scores rose monotonically with Banff acute lesion severity, with 1.5 to 1.8-fold higher odds of more severed g, ptc, i, and t (all P<0.0001), and showed good calibration. Associations remained robust for composite microvascular (g+ptc) and tubulointerstitial (i+t) indices and were strongest for severe g and t, supporting this signature as a noninvasive, quantitative readout of acute rejection pathology with immediate diagnostic applicability.

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Li, C., Schwartz, J. E., Salinas, T., Dadhania, D. M., DeVito, A., Higgins, W., Salvatore, S., Seshan, S. V., Muthukumar, T., Suthanthiran, M.. 2026-07-27. First Order Associations Between Banff Acute Lesions in Kidney Allograft Biopsies and a Urinary Cell Three-Gene Diagnostic Signature. https://doi.org/10.64898/2026.07.22.740171

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