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 of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, 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.

The XV. Banff conference for allograft pathology was held in conjunction with the annual meeting of the American Society for Histocompatibility and Immunogenetics in Pittsburgh, PA (USA) and focused on refining recent updates to the classification, advances from the Banff working groups, and standardization of molecular diagnostics. This report on kidney transplant pathology details clarifications and refinements to the criteria for chronic active (CA) T cell–mediated rejection (TCMR), borderline, and antibody‐mediated rejection (ABMR). The main focus of kidney sessions was on how to address biopsies meeting criteria for CA TCMR plus borderline or acute TCMR. Recent studies on the clinical impact of borderline infiltrates were also presented to clarify whether the threshold for interstitial inflammation in diagnosis of borderline should be i0 or i1. Sessions on ABMR focused on biopsies showing microvascular inflammation in the absence of C4d staining or detectable donor‐specific antibodies; the potential value of molecular diagnostics in such cases and recommendations for use of the latter in the setting of solid organ transplantation are presented in the accompanying meeting report. Finally, several speakers discussed the capabilities of artificial intelligence and the potential for use of machine learning algorithms in diagnosis and personalized therapeutics in solid organ transplantation.

With the development of modern solid-phase assays to detect anti-HLA antibodies and a more precise histological classification, the diagnosis of antibody-mediated rejection (AMR) has become more common and is a major cause of kidney graft loss. Currently, there are no approved therapies and treatment guidelines are based on low-level evidence. The number of prospective randomized trials for the treatment of AMR is small, and the lack of an accepted common standard for care has been an impediment to the development of new therapies. To help alleviate this, The Transplantation Society convened a meeting of international experts to develop a consensus as to what is appropriate treatment for active and chronic active AMR. The aim was to reach a consensus for standard of care treatment against which new therapies could be evaluated. At the meeting, the underlying biology of AMR, the criteria for diagnosis, the clinical phenotypes, and outcomes were discussed. The evidence for different treatments was reviewed, and a consensus for what is acceptable standard of care for the treatment of active and chronic active AMR was presented. While it was agreed that the aims of treatment are to preserve renal function, reduce histological injury, and reduce the titer of donor-specific antibody, there was no conclusive evidence to support any specific therapy. As a result, the treatment recommendations are largely based on expert opinion. It is acknowledged that properly conducted and powered clinical trials of biologically plausible agents are urgently needed to improve patient outcomes.

SummaryBackground and objectives The arteriovenous fistula (AVF) is the preferred hemodialysis access, but AVFfailure rate is high, and complications from AVF placement are rarely reported. There is no clear consensus on predictors of AVF patency. This study determined AVF outcomes and patency predictors at Mayo Clinic Rochester following the Fistula First Initiative.Design, setting, participants, & measurements A retrospective cohort study of AVFs placed at Mayo Clinic from January 2006 through December 2008 was performed. The AVF placement-associated primary and secondary failure rates, complications, interventions, and hospitalizations were examined. Kaplan-Meier survival curves and Cox proportional hazard models were used to determine primary and secondary patency and associated predictors.Results During this time frame, 317 AVFs were placed in 293 individual patients. The primary failure rate was 37.1% after excluding patients not initiated on hemodialysis during follow-up (n ϭ 38) or those with indeterminate outcome (37 lost to follow-up; six died; two transplanted). Of usable AVFs, 11.4% later failed. AVF creation incurred complications and hospitalization in 21.2% and 12.3% of patients, respectively. The risk for reduced primary patency was increased by diabetes (HR, 1.54; 95% CI, 1.14 to 2.07); the risk for reduced primary and secondary patency was decreased with larger arteries (HR, 0.83; 95% CI, 0.73 to 0.94; and HR, 0.69; 95% CI, 0.56 to 0.84, respectively).Conclusions Primary failure remains a major issue in the post-Fistula First era. Complications from AVF placement must be considered when planning AVF placement. Our data demonstrate that artery size is the main predictor of AVF patency.

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This study examined outcomes beyond 1 year in eculizumab‐treated (EC) positive crossmatch kidney transplants (+XMKTx) compared to a historical control group. +XMKTx received desensitization with either plasma exchange (PE) alone (N = 48) or PE and EC (N = 30). EC, given for at least 1 month, was continued in the setting of persistently high DSA (B flow cytometric crossmatch [BFXM] >200) including: 4 weeks (n = 14); 9 weeks (n = 6), 6 months (n = 2), and 12 months (n = 8). All patients had at least 2 years follow‐up. The incidence of acute clinical ABMR was lower in the EC group than controls (6.7% vs. 43.8% p < 0.01). Death‐censored allograft survival was similar between groups. Chronic ABMR was the main cause of graft loss. On 1‐year protocol biopsies, no differences were noted between EC and controls including: cg score >0, 26.7% versus 31.9% (p = 0.62), ptc score ≥ 2, 60.0% versus 60.0% (p = 1.00), or C4d + , 33.8% versus 13.5% (p = 0.08). A persistently high BFXM in EC‐treated patients was associated with cg score >0 at 1 year, while EC appeared to protect against cg if the BFXM remained low. We conclude that despite decreasing acute clinical ABMR rates, EC treatment does not prevent chronic ABMR in recipients with persistently high BFXM after +XMKTx.

Kidney paired donation (KPD) and the new kidney allocation system (KAS) in the United States have led to improved transplantation rates for highly sensitized candidates. We aimed to assess the potential need for other approaches to improve the transplantation rate of highly sensitized candidates such as desensitization. Using the UNOS STAR file, we analyzed transplant rates in a prevalent active waiting‐list cohort as of June 1, 2016, followed for 1 year. The overall transplantation rate was 18.9% (11 129/58769). However, only 9.7% (213/2204) of candidates with a calculated panel reactive antibody ≥99.9% received a transplant, and highly sensitized candidates were less likely to receive a living donor transplant. Among candidates with a CPRA ≥ 99.5% (ie. 100%), only 2.5% of transplants were from living donors (13 total, 7 from KPD). Nearly 4 years after KAS (6/30/2018), 1791 actively wait‐listed candidates had a CPRA of ≥99.9% and 34.6% (620/1791) of these had ≥5 years of waiting time. Thus, despite KPD and KAS, many sensitized candidates have not been transplanted even with prolonged waiting time. We conclude that candidates with a CPRA ≥ 99.9% and sensitized candidates with an incompatible living donor and prolonged waiting time may benefit from desensitization to improve their ability to receive a transplant.

De novo donor specific antibody (dnDSA) is associated with antibody mediated rejection (AMR) and allograft loss, yet the allograft histology associated with dnDSA remains unclear. The aim of this study was to examine the allograft histology associated with dnDSA in patients with serial surveillance biopsies. We retrospectively studied adult conventional solitary kidney transplant recipients from 10/2007–5/2014. DnDSA was new DSA with MFI >1000. The incidence of dnDSA was 7.0%(54/771) over mean follow-up of 4.2±1.9 years. Patients with dnDSA had reduced death-censored allograft survival (87.0% vs. 97.0% no dnDSA, p<0.01). 94% of patients received a biopsy after dnDSA (mean of 3 biopsies/patient). AMR was present in 25.0% and 52.9% of patients at dnDSA detection and at 1 year, respectively. Patients with both class I and II dnDSA had the highest rate of allograft loss. The higher the sum MFI at dnDSA detection, the higher the incidence of AMR. In conclusion, patients with dnDSA without AMR at time of detection may benefit from a follow-up biopsy within 1 year because AMR can be missed initially. Additionally, the dnDSA class and sum MFI at baseline appears to be prognostic. The higher the sum MFI of dnDSA at baseline, the higher the incidence of AMR.