T cell–mediated rejection is a major determinant of inflammation in scarred areas in kidney allografts

Inflammation in fibrosis areas (i‐ IF / TA ) of kidney allografts is associated with allograft loss; however, its diagnostic significance remains to be determined. We investigated the clinicohistologic phenotype and determinants of i‐ IF / TA in a prospective cohort of 1539 kidney recipients undergoing evaluation of i‐ IF / TA and tubulitis in atrophic tubules (t‐ IF / TA ) on protocol allograft biopsies performed at 1 year posttransplantation. We considered donor, recipient, and transplant characteristics, immunosuppression, and histological diagnoses in 2260 indication biopsies performed within the first year posttransplantation. Nine hundred forty‐six (61.5%) patients presented interstitial fibrosis/tubular atrophy ( IF / TA Banff grade > 0) at 1 year posttransplant, among whom 394 (41.6%) showed i‐ IF / TA . i‐ IF / TA correlated with concurrent t‐ IF / TA ( P  < .001), interstitial inflammation ( P  < .001), tubulitis ( P  < .001), total inflammation ( P  < .001), peritubular capillaritis ( P  < .001), interstitial fibrosis ( P  < .001), and tubular atrophy ( P  = .02). The independent determinants of i‐ IF / TA were previous T cell–mediated rejection ( TCMR ) ( P  < .001), BK virus nephropathy ( P  = .007), steroid therapy ( P  = .039), calcineurin inhibitor therapy ( P  = .011), inosine‐5′‐monophosphate dehydrogenase inhibitor therapy ( P  = .011), HLA ‐B mismatches ( P  = .012), and HLA ‐ DR mismatches ( P  = .044). TCMR patients with i‐ IF / TA on posttreatment biopsy (N = 83/136, 61.0%) exhibited accelerated progression of IF / TA over time ( P  = .01) and decreased 8‐year allograft survival (70.8% vs 83.5%, P  = .038) compared to those without posttreatment i‐ IF / TA . Our results support that i‐ IF / TA may represent a manifestation of chronic active TCMR .