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Assessment of the Utility of Kidney Histology as a Basis for Discarding Organs in the US

12/15/2020

 
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New research indicates that analyses of kidney biopsies from deceased donors don’t provide meaningful information beyond standard assessments of donor and recipient characteristics. In addition, the study revealed that relying on these analyses has prompted the discard of many potentially suitable organs for transplantation in the United States. The findings appear in JASN.

Despite a critical scarcity of organs available for transplantation, thousands of deceased donor kidneys are discarded each year in the United States. 


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The Banff 2019 Kidney Meeting Reports

9/20/2020

 
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. 

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Prediction system for risk of allograft loss in patients receiving kidney transplants: international derivation and validation study

3/3/2020

 
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The first universal algorithm for predicting the risk of kidney transplant loss, named iBox, has been developed, validated and just made public by teams from Europe and the US.

​The iBox is designed for clinicians to personalize and improve patient follow-up. The iBox could also accelerate the development of new immunosuppressive treatments by reducing the duration of clinical trials and defining a valid surrogate endpoint.
Chronic kidney disease affects 1 out of 10 people worldwide and is steadily increasing. When it reaches end-stage renal disease and endangers the lives of patients, dialysis or transplantation is required. ​

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Disparities in Acceptance of Deceased Donor Kidneys Between the United States and France and Estimated Effects of Increased US Acceptance

8/26/2019

 
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New publication in JAMA Internal Medicine: The first international analysis of renal transplant patient data shows that a change in allocation criteria in the United States could benefit patients on the waiting list. Thousands more kidneys could be transplanted each year if the United States used, as France does, kidneys from older donors.
Nearly 5,000 people in the United States and 3,500 in Europe die each year waiting for a kidney transplant. Yet, over the same period, in the United States, more than 3,500 available kidneys were discarded. The Journal of the American Medical Association (JAMA) Internal Medicine today published our results, obtained with the help of an international team, that compared the use of kidneys available in the United States and France between 2004 and 2014. ​
Using a new approach based on validated analytical methods and computer simulations, this work revealed that French transplant centres are much more likely to transplant kidneys from older donors than their American counterparts, and that this effectively increases the number of patients transplanted. 

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Archetype Analysis Identifies Distinct Profiles in Renal Transplant Recipients with Transplant Glomerulopathy Associated with Allograft Survival

3/14/2019

 
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New research conducted by the Paris Translational Research Center for Organ Transplantation team could help clinicians determine which patients will have a disease that usually occurs after a kidney transplant and which are at high risk of transplant failure. The results are published today in the prestigious Journal of the American Society of Nephrology (JASN).

Transplant glomerulopathy was first described and characterized 50 years ago. It is a disease associated with the loss of a kidney transplant and common after a transplant. It affects the functional units (i. e. glomeruli) of the transplanted kidney. There is currently no treatment for this heterogeneous disease.

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The Banff 2017 Kidney Meeting Report

12/15/2017

 
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​REVISED DIAGNOSTIC CRITERIA FOR CHRONIC ACTIVE T CELL–MEDIATED REJECTION, ANTIBODY‐MEDIATED REJECTION, AND PROSPECTS FOR INTEGRATIVE ENDPOINTS FOR NEXT‐GENERATION CLINICAL TRIALS
​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.

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Circulating donor-specific anti-HLA antibodies are a major factor in premature and accelerated allograft fibrosis.

9/7/2017

 
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Abstract
Addressing the causes of kidney allograft-accelerated aging is an important challenge for improving long-term transplant outcomes. Here we investigated the role of circulating donor-specific anti-HLA antibodies (HLA-DSAs) in the development and the progression of kidney allograft fibrosis with inclusion of traditional risk factors for allograft fibrosis. We prospectively enrolled 1539 consecutive kidney recipients transplanted in two centers and assessed interstitial fibrosis and tubular atrophy (IF/TA) in biopsies performed at one year post-transplantation. The HLA-DSAs and all traditional determinants of IF/TA were recorded at transplantation and within the first year post-transplantation, including histological diagnoses in 2260 "for cause" biopsies. This identified 498 (32%) patients with severe IF/TA (Banff IF/TA grade 2 or more). HLA-DSAs were significantly associated with severe IF/TA (adjusted odds ratio, 1.53; 95% confidence interval 1.16-2.01) after including 37 determinants. HLA-DSAs remained significantly associated with severe IF/TA in patients without antibody-mediated rejection (adjusted odds ratio 1.54; 1.11-2.14). HLA-DSAs were the primary contributor, being involved in 11% of cases, while T cell-mediated rejection, calcineurin-inhibitor toxicity, acute tubular necrosis, pyelonephritis, and BK virus-associated nephropathy were involved in 9%, 8%, 6%, 5%, and 4% of cases, respectively. One hundred fifty-four patients with HLA-DSA-associated severe IF/TA showed significantly increased microvascular inflammation, transplant glomerulopathy, C4d deposition in capillaries, and decreased allograft survival compared to 344 patients with severe IF/TA without HLA-DSAs. Three hundred seventy-eight patients with post-transplant HLA-DSAs exhibited significantly accelerated progression of IF/TA compared to 1161 patients without HLA-DSAs in the biopsies performed at one year post-transplant and beyond. Thus, circulating HLA-DSAs are major determinants of premature and accelerated allograft fibrosis acting independently of traditional risk factors and antibody-mediated rejection.

Authors: Gosset C, Viglietti D, Rabant M, Vérine J, Aubert O, Glotz D, Legendre C, Taupin JL, Duong Van-Huyen JP, Loupy A, Lefaucheur C.
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Kidney Int. 2017 Sep;92(3):729-742.
PMID: 28554738 ​

Doctor Honoris Causa Award - Phil Halloran

12/14/2016

 
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On December 14th, 2016, Phil Halloran received the award of Doctor Honoris Causa in Paris.
The movie tells the story of renal transplantation and its most famous contributors.
https://vimeo.com/197092951

The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology.

11/10/2016

 
Abstract
A. Loupy,  M. Haas, K. Solez,  L. Racusen, D. Glotz,  D. Seron,  B. J. Nankivell,  R. B. Colvin,  M. Afrouzian, E. Akalin,  N. Alachkar,  S. Bagnasco,  J. U. Becker,  L. Cornell, C. Drachenberg, D. Dragun,  H. de Kort, I. W. Gibson,  E. S. Kraus  C. Lefaucheur,  C. Legendre,  H. Liapis, T. Muthukumar, V. Nickeleit,  B. Orandi, W. Park,  M. Rabant, P. Randhawa,  E. F. Reed,  C. Roufosse,  S. V. Seshan,  B. Sis, H. K. Singh, C. Schinstock,  A. Tambur, A. Zeevi,  M. Mengel.

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.
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Am J Transplant. 2017 Jan;17(1):28-41.
PMID: 27862883
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Figure 1: Molecular lesions and their corresponding histologic lesions in T cell–mediated rejection and antibody‐mediated rejection in kidney allografts. cg, glomerular double contours; cv, vascular fibrous intimal thickening; i, inflammation; ptc, peritubular capillaritis; ti, total inflammation; v, intimal arteritis.

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