The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA) and its relationship to T cell–mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody-mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i-IFTA is associated with reduced graft survival. Furthermore, these groups presented that i-IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i-IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor-specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next-generation clinical trials.

The XIII. Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection, requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i-IFTA score - comprising inflammation within areas of fibrosis and atrophy, and acceptance of transplant arteriolopathy within the descriptions of chronic-active T cell-mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions for TCMR and ABMR in pancreas transplants with specification of vascular lesions as well as prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histological, serological, and molecular diagnostic techniques to produce a consensus-based reporting system that offers: precise composite scores, accurate routine diagnostics, and applicability to next generation clinical trials.

We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post‐KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single‐center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single‐center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17‐fold (95% CI: 1.01–4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post‐KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach.

Pretransplant antibodies, particularly anti-CD40, correlate with risk of recurrent focal segmental glomerulosclerosis after kidney transplant.

Background Mycophenolate mofetil (MMF) side effects often prompt dose reduction or discontinuation, and this MMF dose reduction (MDR) can lead to rejection and possibly graft loss. Unfortunately, little is known about what factors might cause or contribute to MDR. Frailty, a measure of physiologic reserve, is emerging as an important, novel domain of risk in kidney transplantation recipients. We hypothesized that frailty, an inflammatory phenotype, might be associated with MDR. Methods We measured frailty (shrinking, weakness, exhaustion, low physical activity, and slowed walking speed), other patient and donor characteristics, longitudinal MMF doses, and graft loss in 525 kidney transplantation recipients. Time-to-MDR was quantified using an adjusted Cox proportional hazards model. Results By 2 years after transplantation, 54% of frail recipients and 45% of nonfrail recipients experienced MDR; by 4 years, incidence was 67% and 51%. Frail recipients were 1.29 times (95% confidence interval [95% CI], 1.01–1.66; P = 0.04) more likely to experience MDR, as were deceased donor recipients (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.44–2.54, P < 0.001) and older adults (age ≥ 65 vs <65; aHR, 1.47; 95% CI, 1.10–1.96, P = 0.01). Mycophenolate mofetil dose reduction was independently associated with a substantially increased risk of death-censored graft loss (aHR, 5.24; 95% CI, 1.97–13.98, P = 0.001). Conclusion A better understanding of risk factors for MMF intolerance might help in planning alternate strategies to maintain adequate immunosuppression and prolong allograft survival.