Response to treatment and long-term outcomes in kidney transplant recipients with acute T cell-mediated rejection.

Abstract

The recent recognition of complex and chronic phenotypes of T cell-mediated rejection (TCMR) has fostered the need to better evaluate the response of acute TCMR-a condition previously considered to lack relevant consequences for allograft survival-to the standard of care. In a prospective cohort of kidney recipients (n=256) with biopsy-proven acute TCMR receiving corticosteroids, we investigated clinical, histological, and immunological phenotypes at the time of acute TCMR diagnosis and 3months posttreatment. Independent posttreatment determinants of allograft loss included the glomerular filtration rate (GFR) (HR=0.94; 95% CI=0.92-0.96; P<.001), proteinuria (HR=1.40; 95% CI=1.10-1.79; P=.007), time since transplantation (HR=1.02; 95% CI=1.00-1.03; P=.016), peritubular capillaritis (HR=2.27; 95% CI=1.13-4.55; P=.022), interstitial inflammation in sclerotic cortical parenchyma (i-IF/TA) (HR=1.87; 95% CI=1.08-3.25; P=.025), and donor-specific anti-HLA antibodies (DSAs) (HR=2.67; 95% CI=1.46-4.88; P=.001). Prognostic value was improved using a composite evaluation of response to treatment versus clinical parameters only (cNRI=0.68; 95% CI=0.41-0.95; P<.001). A classification tree for allograft loss identified five patterns of response to treatment based on the posttreatment GFR, i-IF/TA, and anti-HLA DSAs (cross-validated accuracy=0.80). Compared with responders (n=155, 60.5%), nonresponders (n=101, 39.5%) had a higher incidence of de novo DSAs, antibody-mediated rejection, and allograft loss at 10years (P<.001 for all comparisons). Thus, clinical, histological, and immunological assessment of response to treatment of acute TCMR revealed different profiles of the response to treatment with distinct outcomes.