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

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.