Does tubulitis without interstitial inflammation represent borderline acute T cell mediated rejection?

Tubulitis without interstitial inflammation (Banff i0), termed "isolated tubulitis" (ISO-T), has been controversially included within the Banff "borderline" category of acute T cell mediated rejection (TCMR). This single-center, retrospective, observational study of 2055 consecutive biopsies from 775 recipients, determined the clinical significance of ISO-T. ISO-T prevalence was 19.1%, comprising mild tubulitis (i0t1) in 97.2%. Independent clinical predictors of tubulitis were HLA mismatch, prior TCMR and antibody-mediated rejection, pulse corticosteroids, and BKVAN (P = .006 to P < .001 by multivariable analysis). Histological associations of tubulitis included interstitial inflammation, peritubular capillaritis, tubular atrophy, and SV40T (P = .005 to <.001). The dominant pathological diagnoses in ISO-T (n = 393) were interstitial fibrosis/tubular atrophy (IF/TA, 44.5%) or normal/minimal (31.8%). Subanalysis of ISO-T from indication biopsies (n = 107) found acute tubular injury (37.4%), IF/TA (28.0%), normal/minimal (12.1%), acute rejection (9.3%, vascular or antibody), chronic-active TCMR (2.8%), and BKVAN (5.6%). Allograft function of ISO-T frequently improved, affected by early biopsy timing and underlying disease diagnosis. Subsequent histology of 1197 ISO-T biopsy-pairs was generally benign. The 1- and 5-year death-censored graft survivals of ISO-T were 98.8% and 92.7%. In summary, tubulitis without inflammation does not represent borderline TCMR. We suggest its removal from the borderline category, and reinstatement of i1 as the diagnostic threshold.