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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.

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. This study of two indication‐biopsy cohorts questions the Banff diagnostic category of chronic active T cell–mediated rejection. Naesens et al. comment on page 1689.

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 DSAat 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+ DSAhad 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 DSAconfirmed 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 DSAwith 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 DSAand where an allograft biopsy is not accessible. This study evaluates the prognostic value of a C3d assay in a cohort of kidney recipients, demonstrating that while C3d+ donor‐specific antibodies associate with inferior graft survival compared to C3d– antibodies, the assay provides marginal value in the risk stratification of patients with strong donor‐specific antibodies.

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 (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.

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.

Renal transplant recipients who are chronically immunosuppressed by drugs are at a higher risk of developing malignancies. Commonly observed malignancies are several forms of posttransplant lymphoproliferative disorders (PTLD), skin, lip and gynaecological cancers. The risk is associated with many risk factors including the extent of immunosuppression. Mycophenolate mofetil (MMF) is an immunosuppressant, indicated for the prophylaxis of organ rejection in patients receiving allogenic renal and heart transplants. During the European approval of MMF for renal transplantation, the question was raised as to whether the use of MMF was associated with an increased risk of PTLD in comparison with alternate immunosuppressive regimens. In response, F. Hoffman‐La Roche Ltd set up a prospective observational cohort study with a companion case–control study. This paper describes the objectives and the methods of these studies along with the rationale of the methodology. Copyright © 1999 John Wiley & Sons, Ltd.

Renal transplant recipients who are chronically immunosuppressed by drugs are at a higher risk of developing malignancies. Commonly observed malignancies are several forms of posttransplant lymphoproliferative disorders (PTLD), skin, lip and gynaecological cancers. The risk is associated with many risk factors including the extent of immunosuppression. Mycophenolate mofetil (MMF) is an immunosuppressant, indicated for the prophylaxis of organ rejection in patients receiving allogenic renal and heart transplants. During the European approval of MMF for renal transplantation, the question was raised as to whether the use of MMF was associated with an increased risk of PTLD in comparison with alternate immunosuppressive regimens. In response, F. Hoffman-La Roche Ltd set up a prospective observational cohort study with a companion case–control study. This paper describes the objectives and the methods of these studies along with the rationale of the methodology. Copyright © 1999 John Wiley & Sons, Ltd.

As reported to the UNOS Kidney Transplant Registry from 1988 through 1994, 544 first cadaveric kidney graft recipients have been discharged with maintenance tacrolimus FK506 therapy. Total followup data was available on 38,057 first cadaveric kidney transplants from 224 centers reporting at least 10 grafts each to the Registry. We examined the effects of FK506 on short and longterm renal graft outcomes and compared its effect with that of cyclosporine CsA. Three drug categories FK506, CsA, and Other were defined using therapies through discharge i.e., grafts surviving more than 15 days. The 1year graft survival rate of 2366 recipients receiving Other therapies was 69.2±1.0. By comparison, both FK506 and CsA recipients demonstrated significantly improved early graft function 1yr survival rates of 91.1±1.3 and 86.6±0.2, respectively. The longterm graft survival, as measured by halflives, varied little 89 yr between Other and CsA groups, but was significantly P0.04 increased for FK506 patients to 14yrs. CsA usage was reported by all 224 transplant centers, whereas FK506 was administered at only 24 11 centers. Using multivariate methods, a drug regimen's graft survival rate was adjusted for center effects and 19 covariates. The adjusted FK506 and CsA cadaveric graft survival rates at 1 and 3 years mirrored their unadjusted rates, indicating that demographic differences did not confound our results. Based on this study, FK506 appears to be the first therapeutic agent to significantly improve longterm kidney graft survival rates.