Significance of revised criteria for chronic active T cell–mediated rejection in the 2017 Banff classification: Surveillance by 1-year protocol biopsies for kidney transplantation

Abstract

Diagnostic criteria for chronic active T cell-mediated rejection (CA-TCMR) were revised in the Banff 2017 consensus, but it is unknown whether the new criteria predict graft prognosis of kidney transplantation. We enrolled 406 kidney allograft recipients who underwent a 1-year protocol biopsy (PB) and investigated the diagnostic significance of Banff 2017. Interobserver reproducibility of the 3 diagnosticians showed a substantial agreement rate of 0.68 in Fleiss's kappa coefficient. Thirty-three patients (8%) were classified as CA-TCMR according to Banff 2017, and 6 were previously diagnosed as normal, 12 as acute TCMR, 10 with borderline changes, and 5 as CA-TCMR according to Banff 2015 criteria. Determinant factors of CA-TCMR were cyclosporine use (vs tacrolimus), previous acute rejection, and BK polyomavirus-associated nephropathy. In survival analysis, the new diagnosis of CA-TCMR predicted a composite graft endpoint defined as doubling serum creatinine or death-censored graft loss (logrank test, P < .001). In multivariate analysis, CA-TCMR was associated with the second highest risk of the composite endpoint (hazard ratio: 5.42; 95% confidence interval, 2.02-14.61; P < .001 vs normal) behind antibody-mediated rejection. In conclusion, diagnosis of CA-TCMR in Banff 2017 may facilitate detecting an unfavorable prognosis of kidney allograft recipients who undergo a 1-year PB.

Chronic active T cell–mediated rejection is variably responsive to immunosuppressive therapy

“…VL Kung et al: CA TCMR is variably responsive to treatment treated because of lack of evidence on treatment efficacy. 26,27 As a center that has diagnosed CA TCMR since its inclusion in the Banff classification but does not treat patients with this diagnosis in a uniform manner, we show, in an albeit small cohort of only 44 treated, pure CA TCMR cases without ABMR or intimal arteritis, a 20% response rate (9 of 44 with $50% eGFR recovery at 4 weeks after biopsy) to immunosuppressive therapy. This preliminary finding supports the notion that increased immunosuppression might be efficacious in a subset of CA TCMR cases.…”

Does the definition of chronic active T cell–mediated rejection need revisiting?

“…In protocol biopsies performed at 1 year, Nakagawa et al demonstrated a low number of cases with CA-TCMR grade I (28/406 = 6.9%) with 22 of these 28 cases also meeting criteria for acute TCMR or borderline. 2 In support of the concept of CA-TCMR its diagnosis was associated with tubulitis in IFTA, evolved from smoldering inflammation below Banff thresholds for acute rejection (i.e., borderline) and was associated with increased risk of graft failure, independent of ABMR.…”

“…The Banff 2017 report explicitly states that further studies on this newly defined Banff category were necessary. 1 In response, several recent studies, 2,3 and that of Helgeson et al in the current issue of AJT, 4 have evaluated the phenotype of CA-TCMR in more detail in large, well-annotated cohorts.…”

Treatment of chronic active T cell‐mediated rejection after kidney transplantation: A retrospective cohort study of 37 transplants

“…The prognosis for allograft survival with a diagnosis of CA‐TCMR is considered poor. Our previous study 3 reported that the revised criteria from Banff 2015 to 2017 increased the incidence of CA‐TCMR by 1‐year protocol biopsy from 1% to 8%. In addition, the revised CA‐TCMR criteria were associated with a 5.42‐fold risk of a composite endpoint defined as a two‐fold increase in serum creatinine compared with the level in normal tissue or censored allograft loss and indicated that CA‐TCMR is the second poorest graft prognostic diagnosis after antibody‐mediated rejection.…”