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Intimal vascular lesions are considered features of acute T-cell-mediated rejection yet can occur in the absence of tubulointerstitial inflammation, termed isolated 'v' lesions. The clinical significance of these lesions is unclear. The diagnosis requires a biopsy with the presence of arteries. The frequency of adequate biopsies was analysed in 89 renal transplant biopsies from 57 paediatric renal allograft recipients, and the incidence of isolated endarteritis was determined. 60 (67%) biopsies contained an artery and of these, isolated 'v' lesions occurred in 6 (10%). 5 (83%) biopsies with isolated 'v' lesions were associated with positive DSA, suggesting that these lesions may represent acute antibody-mediated rejection. Patients with vessel-negative biopsies had an increased decline in eGFR (median −20.5, IQR −24.4 to 1.2 ml/min/1.73 m2 vs. −9.6, IQR −78.7 to −6.8 ml/min/1.73 m2; P = 0.01). Patients with vessel-negative biopsies were more likely to have repeat biopsy for ongoing allograft dysfunction, (25.0% vs. 2.4%; P < 0.01). The data suggest that isolated 'v' lesions are more common than previously thought. A significant proportion of biopsies classified as 'normal' or 'borderline change' in the absence of a large vessel may represent undiagnosed acute rejection. This may result in suboptimal therapy with possible adverse effects on renal outcome. [ABSTRACT FROM AUTHOR]

Background. The term chronic allograft nephropathy (CAN) was deleted in the Eighth Banff Classification and two new categories were introduced: chronic T-cell-mediated rejection (CTMR) and chronic active humoral rejection (CAHR). The aim of this study was to revise our CAN cases diagnosed in the last 4 years, analyse allograft survival rates and identify types of infiltrating cells in the different settings.Methods. Seventy-nine patients with biopsy-proven CAN were examined and classified into four groups according to the Banff 2005 criteria: CTMR, CAHR, chronic calcineurin inhibitor toxicity (CNITOX) and interstitial fibrosis and tubular atrophy not otherwise specified (NOS). CD4, CD8, CD20, CD68, CD103, Foxp3 and IL-17 protein expression and C4d deposits were investigated.Results. We diagnosed 20 CTMR, 13 CAHR, 28 CNITOX, and 18 NOS. Death-censored graft survival at 4 years from renal biopsy was worse in CAHR compared with the other types of chronic injury. Glomerular CD8+ cells were increased in CTMR vs CNITOX and NOS. Interstitial CD4+ and CD8+ cells were increased in CTMR vs CNITOX. CD68+ cells in glomerular and peritubular capillaries were higher in CAHR vs CNITOX, CTMR and NOS. CD103+ cells were higher in cases with tubulitis than in those without. T regulatory and T helper 17 cells were rarely observed in the different settings.Conclusions. Graft survival was worse in patients with CAHR. The presence of any grade transplant glomerulopathy and chronic allograft vasculopathy are poorer prognostic factors. Infiltrating CD8+, CD103+ and CD4+ cells may help to differentiate CTMR from other types of chronic injury, thus improving diagnostic/prognostic features of biopsy in patients with chronic allograft dysfunction. [ABSTRACT FROM AUTHOR]

Introduction: The diagnosis of late antibody-mediated rejection (AMR) is compromised by frequent absence of C4d in peritubular capillaries (C4d ptc ), termed "C4d-negative" AMR. We hypothesized that glomerular capillary C4d (C4d glom ) reflected endothelial interaction with antibody and could improve immunologic classification of transplant glomerulopathy (TG)., Methods: We evaluated C4d using immunoperoxidase in 3524 consecutive, kidney transplant biopsies from a single center., Results: C4d glom was detected in 16.5% and C4d ptc in 9.9% of biopsies. C4d glom occurred in 60.3% of TG ( n = 174) and was absent in normal glomeruli. Epidemiologic risk factors for C4d glom were younger, female, living-donor recipients with early AMR, prior treated rejection, and late presentation using multivariable analysis. Semiquantitative C4d glom score correlated with donor specific antibody (DSA) level, C4d ptc , microvascular inflammation (MVI), Banff cg scores, renal dysfunction, and proteinuria. Principal component analysis colocalized C4d glom with histologic AMR. Multivariable analysis of TG found DSA, C4d ptc , and post-transplant time associated with C4d glom . Addition of C4d glom into Banff chronic AMR schema improved its diagnostic sensitivity for TG (verified by electron microscopy [EM]) from 22.2% to 82.4% and accuracy from 59.6% to 93.9%, compared with Banff 2019 using only C4d ptc . Tissue C4d glom and chronic AMR diagnosis incorporating C4d glom were associated with death-censored allograft failure in TG ( P  < 0.001), independent of the severity of glomerulopathy and chronic interstitial fibrosis., Conclusion: C4d glom is a promising diagnostic biomarker of endothelial interaction with antibody which substantially improved test performance of the Banff schema to correctly classify TG by pathophysiology and prognosticate graft loss. We recommend routine C4d immunoperoxidase to minimize underdiagnosis of late AMR in TG., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Background and Objectives: The published tissue adequacy requirement of kidney medulla for BK virus allograft nephropathy diagnosis lacks systematic verification and competes against potential increased procedural risks from deeper sampling., Design, Setting, Participants, & Measurements: We evaluated whether the presence of kidney medulla improved the diagnostic rate of BK nephropathy in 2244 consecutive biopsy samples from 856 kidney transplants with detailed histologic and virologic results., Results: Medulla was present in 821 samples (37%) and correlated with maximal core length ( r =0.35; P <0.001). BK virus allograft nephropathy occurred in 74 (3% overall) but increased to 5% (42 of 821) with medulla compared with 2% (32 of 1423) for cortical samples ( P <0.001). Biopsy medulla was associated with infection after comprehensive multivariable adjustment of confounders, including core length, glomerular number, and number of cores (adjusted odds ratio, 1.81; 95% confidence interval, 1.02 to 3.21; P =0.04). In viremic cases ( n =275), medulla was associated with BK virus nephropathy diagnosis (39% versus 19% for cortex; P <0.001) and tissue polyomavirus load (Banff polyomavirus score 0.64±0.96 versus 0.33±1.00; P =0.006). Biopsy medulla was associated with BK virus allograft nephropathy using generalized estimating equation (odds ratio, 2.04; 95% confidence interval, 1.05 to 3.96; n =275) and propensity matched score comparison (odds ratio, 2.24; 95% confidence interval, 1.11 to 4.54; P =0.03 for 156 balanced pairs). Morphometric evaluation of Simian virus 40 large T immunohistochemistry found maximal infected tubules within the inner cortex and medullary regions ( P <0.001 versus outer cortex)., Conclusions: Active BK virus replication concentrated around the corticomedullary junction can explain the higher detection rates for BK virus allograft nephropathy with deep sampling. The current adequacy requirement specifying targeting medulla can be justified to minimize a missed diagnosis from undersampling., (Copyright © 2020 by the American Society of Nephrology.)

Pancreas transplantation is an effective therapy for diabetic patients, which can significantly improve the survival rate and quality of life of diabetic patients. According to the international registration of pancreas transplantation center, the global total pancreas transplantation has reached more than 80,000 cases by 2017, including pure pancreas transplantation and simultaneous pancreas-kidney transplantation (SPK). With the development and application of a new type of immunosuppressant, with the gradual maturity of organ preservation technology and surgical technology, the pancreas transplantation has rapidly on a global scale. However, pancreas transplantation still has more problems than limit its development compared with other organ transplantation. For example, the early diagnosis and treatment of pancreatic rejection are of considerable significance to the prognosis of pancreas transplantation. Some surveillance methods of diagnosis have been used increasingly, among which the histopathological diagnosis is particularly important. The first Banff schema for the histological diagnosis of pancreas rejection has been published, which primarily dealt with the diagnosis of acute T-cell-mediated rejection (ACMR). In recent years, antibody-mediated rejection (AMR) has been more emphasized as the primary cause of graft failure. The Banff pancreas allograft rejection grading schema was updated in 2011 by a broad-based multidisciplinary panel, presenting comprehensive guidelines for the diagnosis of AMR., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2019 Gland Surgery. All rights reserved.)

Increasing interstitial fibrosis (IF) in native and kidney transplant biopsies is associated with functional decline and serves as a clinical trial end point. A Banff 2009 Conference survey revealed a range in IF assessment practices. Observers from multiple centers were asked to assess 30 renal biopsies with a range of IF and quantitate IF using two approaches on trichrome, Periodic acid-Schiff (PAS) and computer-assisted quantification of collagen III immunohistochemistry (C-IHC) slides, as well as assessing percent of cortical tubular atrophy% (TA%) and Banff total cortical inflammation score (ti-score). C-IHC using whole slide scans was performed. C-IHC assessment showed a higher correlation with organ function (r = -0.48) than did visual assessments (r = -0.32--0.42); computerized and visual C-IHC assessment also correlated (r = 0.64-0.66). Visual assessment of trichrome and C-IHC showed better correlations with organ function and C-IHC, than PAS, TA% and ti-score. However, visual assessment of IF, independent of approach, was variable among observers, and differences in correlations with organ function were not statistically significant among C-IHC image analysis and visual assessment methods. C-IHC image analysis correlated among three centers (r > 0.90, p < 0.0001, between all centers). Given the difficulty of visual IF assessment standardization, C-IHC image could potentially accomplish standardized IF assessment in multicenter settings., (© Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.)