Carol Li, Joseph E Schwartz, Thalia Salinas, Darshana M Dadhania, Alex DeVito, William Higgins, Steven Salvatore, Surya V Seshan, Vijay K Sharma, Thangamani Muthukumar, Manikkam Suthanthiran
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.