The Banff 2022 Kidney Meeting Report: Re-Appraisal of Microvascular Inflammation and the Role of Biopsy-Based Transcript Diagnostics.

The XVI-th Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from 19th-23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30 anniversary of the first Banff Classification, pre-meeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis.

Early and Late Microvascular Inflammation Have Differing Etiological Causes and Clinical Expression.

Background: Microvascular inflammation (MVI) is an important pathological feature of antibody-mediated rejection (AMR). How posttransplant time affects its clinicopathological expression is little understood.

Methods: This retrospective, single-center study screened 3398 kidney transplant biopsies and dichotomized 202 MVI ≥ 2 (Banff glomerulitis + peritubular capillaritis ≥ 2) samples by 9-mo median incidence time for comparison.

The relationship of microvascular inflammation with antibody-mediated rejection in kidney transplantation.

Microvascular inflammation (MVI) is a key diagnostic feature of antibody-mediated rejection (AMR); however, recipients without donor-specific antibodies (DSA) defy etiologic classification using C4d staining of peritubular capillaries (C4d) and conventional DSA assignment. We evaluated MVI ≥ 2 (Banff g + ptc ≥ 2) using Banff 2019 AMR (independent of MVI ≥ 2 but including C4d) with unconventional endothelial C4d staining of glomerular capillaries (C4d) and - arterial endothelium and/or intima (C4d) using tissue immunoperoxidase, shared-eplet and subthreshold DSA (median fluorescence intensity, [MFI] 100-499), and capillary ultrastructure from 3398 kidney transplant samples for evidence of AMR. MVI ≥ 2 (n = 202 biopsies) from 149 kidneys (12.

The Effects of COVID-19 in Kidney Transplantation: Evidence From Tissue Pathology.

Background: The biological effects of SARS-CoV-2 infection in transplanted kidneys are uncertain with little pathological information.

Methods: This single-center, prospective observational study evaluated kidney transplant biopsies from recipients of deceased donors with COVID-19, current recipients contracting SARS-CoV-2 Omicron variant in 2022, against prior BK virus (BKV) infection and uninfected (without SARS-CoV-2 or BKV) samples, as respective positive and negative comparators (n = 503 samples).

Results: We demonstrated nonvirus tubular injury in implanted tissue from infected donors and prevalent recipients with mild acute COVID-19 and acute kidney injury, excluding direct viral infection as a cause of kidney damage.

Banff 2022 Vascularized Composite Allotransplantation Meeting Report: Diagnostic criteria for vascular changes.

As more data become available, the Banff 2007 working classification of skin-containing vascularized composite allograft (VCA) pathology is expected to evolve and develop. This report represents the Banff VCA Working Group's consensus on the first revision of the 2007 scoring system. Prior to the 2022 Banff-CanXadian Society of Transplantation Joint Meeting, 83 clinicians and/or researchers were invited to a virtual meeting to discuss whether the 2007 Banff VCA system called for a revision.

The Banff 2022 Kidney Meeting Report: Reappraisal of microvascular inflammation and the role of biopsy-based transcript diagnostics.

The XVI-th Banff Meeting for Allograft Pathology was held at Banff, Alberta, Canada, from 19th to 23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30th anniversary of the first Banff Classification, premeeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis.

Race-free estimated glomerular filtration rate equation in kidney transplant recipients: development and validation study.

Objective: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients.

Design: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials).

Participants: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021.

The Clinical and Pathologic Phenotype of Antibody-Mediated Vascular Rejection Diagnosed Using Arterial C4d Immunoperoxidase.

Introduction: The diagnosis of antibody-mediated vascular rejection (AM-VR) should be reliable and accurate. We hypothesized that arterial C4d (C4d) immunoperoxidase deposition represents endothelial interaction with antibody.

Methods: From 3309 consecutive, kidney transplant biopsies from a single center, 100 vascular rejection (VR) cases were compared against rejection without arteritis ( = 540) and normal controls ( = 1108).

Glomerular C4d Immunoperoxidase in Chronic Antibody-Mediated Rejection and Transplant Glomerulopathy.

Introduction: The diagnosis of late antibody-mediated rejection (AMR) is compromised by frequent absence of C4d in peritubular capillaries (C4d), termed "C4d-negative" AMR. We hypothesized that glomerular capillary C4d (C4d) 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.

The Pathological and Clinical Diversity of Acute Vascular Rejection in Kidney Transplantation.

Background: Vascular rejection (VR) is characterized by arteritis, steroid resistance, and increased graft loss but is poorly described using modern diagnostics.

Methods: We screened 3715 consecutive biopsies and retrospectively evaluated clinical and histological phenotypes of VR (n = 100) against rejection without arteritis (v0REJ, n = 540) and normal controls (n = 1108).

Results: Biopsy sample size affected the likelihood of arterial sampling, VR diagnosis, and final Banff v scores ( P < 0.

Usefulness of Left Atrial Strain to Predict End Stage Renal Failure in Patients With Chronic Kidney Disease.

Left atrial (LA) enlargement predicts adverse cardiovascular events in patients with chronic kidney disease (CKD). The aim of our study was to evaluate the value of LA reservoir strain, a novel measure of LA function, as a prognostic marker for adverse renal outcomes. A total of 280 patients (65.

Polyoma BK Virus in Kidney Transplant Recipients: Screening, Monitoring, and Management.

Polyomavirus BK virus (BKPyV) infection is an important complication of kidney transplantation and allograft failure. The prevalence of viremia is 10%-15%, compared with BK-associated nephropathy (BKPyVAN) at 3%-5%. Given that there are no effective antiviral prophylaxis or treatment strategies for BKPyVAN, active screening to detect BKPyV viremia is recommended, particularly during the early posttransplant period.

How unmeasured muscle mass affects estimated GFR and diagnostic inaccuracy.

Background: Estimated glomerular filtration (eGFR) results based on serum creatinine are frequently inaccurate with differences against measured GFR (mGFR) often attributed to unmeasured non-functional factors, such as muscle mass.

Methods: The influence of muscle mass (measured by dual-energy x-ray absorptiometry, DEXA) on eGFR error (eGFR-mGFR) was evaluated using isotopic mGFR (Tc DTPA plasma clearance) in 137 kidney transplant recipients. Serum creatinine was measured by isotopic-calibrated enzymatic analysis, converted to eGFR using Chronic Kidney Disease EPIdemiology (CKD-EPI) formula, then unindexed from body surface area.

Renal tubular cell binding of β-catenin to TCF1 versus FoxO1 is associated with chronic interstitial fibrosis in transplanted kidneys.

β-Catenin is an important co-factor which binds multiple transcriptional molecules and mediates fibrogenic signaling pathways. Its role in kidney transplantation is unknown. We quantified binding of β-catenin within renal tubular epithelial cells to transcription factors, TCF1 and FoxO1, using a proximity ligation assay in 240 transplanted kidneys, and evaluated their pathological and clinical outcomes.

The meaning of borderline rejection in kidney transplantation.

Borderline T cell-mediated rejection is a diagnostic category of the Banff schema that uses a lower diagnostic threshold. Subclinical borderline T cell-mediated rejection detected by surveillance sampling is not entirely benign. Studies demonstrate increased rates of late rejection, progressive nephron loss, functional impairment, donor-specific antibody formation, and allograft failure.

The Importance of Kidney Medullary Tissue for the Accurate Diagnosis of BK Virus Allograft Nephropathy.

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 (=0.

Relative survival and quality of life benefits of pancreas-kidney transplantation, deceased kidney transplantation and dialysis in type 1 diabetes mellitus-a probabilistic simulation model.

For patients with type 1 diabetes mellitus who progress to the point of requiring renal replacement therapy, the relative benefits of simultaneous pancreas and kidney transplantation (SPK) and deceased donor kidney transplantation across different age categories compared to dialysis are uncertain. Using Australian and New Zealand registry data from 2006 to 2016, a probabilistic Markov model (n = 10 000) was built comparing patient survival between SPK and deceased donor kidney transplantation with dialysis. Compared to dialysis, the average life years saved (LYS) and quality-adjusted life years (QALY) for SPK and deceased donor kidney transplantation were 5.

Validation of phospholipase A receptor direct immunofluorescence staining in the diagnosis of primary membranous glomerulonephritis.

Distinguishing between primary and secondary subtypes of membranous glomerulonephritis (MGN) is critical for its clinical management. We prospectively compared direct immunofluorescence (DIF) staining for phospholipase A receptor (PLAR) on frozen renal biopsy with the presence of detectable serum PLAR antibody assessed by enzyme linked immunosorbent assay (ELISA) in the diagnosis of primary MGN. Forty-six patients with biopsy-proven MGN were enrolled from April 2017 to June 2019 with 31/46 (67.

The Banff 2019 Kidney Meeting Report (I): Updates on and clarification of criteria for T cell- and antibody-mediated rejection.

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).

Blocking thrombospondin-1 signaling via CD47 mitigates renal interstitial fibrosis.

Acute kidney injury triggers a complex cascade of molecular responses that can culminate in maladaptive repair and fibrosis. We have previously reported that the matrix protein thrombospondin-1 (TSP1), binding its high affinity its receptor CD47, promotes acute kidney injury. However, the role of this pathway in promoting fibrosis is less clear.

Deep Sequencing of Urine Specimens Detects Two BK Polyomavirus Genotypes in a Hematopoietic Stem Cell Transplant Recipient.

BK polyomavirus (BKPyV) is an important pathogen in transplant recipients. We report four draft BKPyV genomes, three of BKPyV genotype I (subtype I-b2) (AUS-105, AUS-106, and AUS-108) and one of genotype II (AUS-107). These draft genomes were identified in longitudinal urine samples collected from a single hematopoietic stem cell transplant recipient.