i-IFTA and chronic active T cell-mediated rejection: A tale of 2 (DeKAF) cohorts.

Inflammation in areas of fibrosis (i-IFTA) in posttransplant biopsies is part of the diagnostic criteria for chronic active TCMR (CA TCMR -- i-IFTA ≥ 2, ti ≥ 2, t ≥ 2). We evaluated i-IFTA and CA TCMR in the DeKAF indication biopsy cohorts: prospective (n = 585, mean time to biopsy = 1.7 years); cross-sectional (n = 458, mean time to biopsy = 7.8 years). Grouped by i-IFTA scores, the 3-year postbiopsy DC-GS is similar across cohorts. Although a previous acute rejection episode (AR) was more common in those with i-IFTA on biopsy, the majority of those with i-IFTA had not had previous AR. There was no association between type of previous AR (AMR, TCMR) and presence of i-IFTA. In both cohorts, i-IFTA was associated with markers of both cellular (increased Banff i, t, ti) and humoral (increased g, ptc, C4d, DSA) activity. Biopsies with i-IFTA = 1 and i-IFTA ≥ 2 with concurrent t ≥ 2 and ti ≥ 2 had similar DC-GS. These results suggest that (a) i-IFTA≥1 should be considered a threshold for diagnoses incorporating i-IFTA, ti, and t; (b) given that i-IFTA ≥ 2,t ≥ 2, ti ≥ 2 can occur in the absence of preceding TCMR and that the component histologic scores (i-IFTA,t,ti) each indicate an acute change (albeit i-IFTA on the nonspecific background of IFTA), the diagnostic category "CA TCMR" should be reconsidered.

Clinical utility of complement-dependent C3d assay in kidney recipients presenting with late allograft dysfunction.

The objective of this study was to evaluate the utility of a complement-dependent C3d assay to risk stratify donor-specific antibodies (DSA) in a multicenter cohort of kidney recipients presenting with new-onset clinical dysfunction. A total of 106 subjects with evidence of DSA at a mean period of 5.3 ± 5.0 years posttransplant underwent testing using C3d reagents. C3d positivity was strongly associated with both the peak and sum IgG DSA MFI, with 98.3% (n = 57/58) of strongly reactive sera (peak MFI > 10 000) eliciting a positive signal. Patients with C3d+ DSA had a higher creatinine (P = .03), more significant graft fibrosis (P = .035), and a faster rate of graft loss posttest compared to those with C3d- DSA (P = .05). Subanalysis of patients with low-moderate level DSA confirmed the inferior outcome associated with C3d positivity. Despite the prognostic value of C3d as a stand-alone test, the assay did not provide independent risk prediction after incorporation of graft fibrosis in a multivariate model (P = .94). Overall, C3d offered limited discriminatory value for strong DSA with peak IgG MFI > 10 000 and in patients where histologic data is available, but its utilization may be considered in those with low-moderate level DSA and where an allograft biopsy is not accessible.

Antibody-mediated rejection criteria - an addition to the Banff 97 classification of renal allograft rejection.

Antibody-mediated rejection (AbAR) is increasingly recognized in the renal allograft population, and successful therapeutic regimens have been developed to prevent and treat AbAR, enabling excellent outcomes even in patients highly sensitized to the donor prior to transplant. It has become critical to develop standardized criteria for the pathological diagnosis of AbAR. This article presents international consensus criteria for and classification of AbAR developed based on discussions held at the Sixth Banff Conference on Allograft Pathology in 2001. This classification represents a working formulation, to be revisited as additional data accumulate in this important area of renal transplantation.