The 2017 Banff meeting has focused on the importance of defining the potential role of i-IF/TA as a component of the T cell-mediated rejection (TCMR) process in kidney allografts. We investigated the clinical value of i-IF/TA for evaluating the response to standard treatment of TCMR in kidney recipients.

Among 1916 kidney recipients transplanted between 2004 and 2010, we prospectively included all patients with biopsy-proven acute TCMR within the first year post-transplant, who received standardized treatment by steroids pulses and rATG in refractory cases. Patients were systematically assessed at the time of diagnosis and 3 months post-treatment for GFR, proteinuria, histology (including i-IF/TA Banff score) and anti-HLA DSAs, and followed up to 10 years to assess graft survival.

We included 172 patients with biopsy-proven acute TCMR who received standard treatment. The distribution of TCMR grades was: 52 (30%) grade IA, 65 (38%) grade IB, 37 (22%) grade IIA, 11 (6%) grade IIB and 7 (4%) grade III TCMR. After TCMR treatment, patients showed increased GFR (p<0.001), decreased proteinuria (p<0.001), interstitial inflammation (p<0.001), tubulitis (p<0.001) and intimal arteritis (p<0.001), worsening IF/TA (p<0.001) and arteriosclerosis (p<0.001). Patients with post-treatment i-IF/TA (N=89, 52%) showed decreased 10-year graft survival compared to patients without post-treatment i-IF/TA (N=83, 48%): 64% vs 89%, p<0.001. In multivariable analysis, the independent predictors of graft loss measured at the time of post-treatment evaluation were the presence of i-IF/TA (HR=3.4, p=0.005), the presence of transplant glomerulopathy (HR=2.4, p=0.001), GFR (HR=0.97, p=0.010) and the presence of anti-HLA DSA (HR=2.3, p=0.021). Patients with post-treatment i-IF/TA showed higher incidence of de novo DSA at 1 year post-transplantation (24% vs 6%, p=0.001) and accelerated progression of IF/TA up to 1000 days after transplantation (p=0.01 in mixed-effects model) on biopsies performed at any time after transplantation (N=704) compared to patients without post-treatment i-IF/TA.

The presence of i-IF/TA after standard treatment of acute TCMR is associated with the occurrence of de novo DSA, accelerated progression of interstitial fibrosis and graft loss, and may identify patients with persisting active TCMR in whom additional therapies should be considered.

CITATION INFORMATION: Viglietti D., Aubert O., Duong Van Huyen J-.P., Loupy A., Lefaucheur C. Inflammation in Scarred Areas (i-IF/TA): Defining the Response to Standard Treatment of T Cell-Mediated Rejection in Kidney Recipients Am J Transplant. 2017;17 (suppl 3).

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