Tacrolimus to belatacept conversion in proteinuric kidney transplant recipients.

Background: Proteinuria is associated with worse allograft outcomes in kidney transplant recipients (KTRs) and treatment strategies are limited. We examined the outcomes of calcineurin inhibitor (CNI) to belatacept conversion in proteinuric KTRs.

Methods: In a pilot phase II single-arm multicenter prospective trial, we recruited adult KTRs >6 months post-kidney transplantation with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.

Evaluation of a Decentralized Donor-Derived Cell-Free DNA Assay for Kidney Allograft Rejection Monitoring.

Donor-derived cell-free DNA (dd-cfDNA) is an emerging non-invasive biomarker for allograft injury detection. This study aimed to evaluate a new, decentralized dd-cfDNA testing kit against a centralized dd-cfDNA testing service broadly utilized in the United States. Kidney transplant recipients with decentralized and centralized dd-cfDNA measurements and concomitant kidney allograft biopsies were included in the study.

Microvascular Inflammation of Kidney Allografts and Clinical Outcomes.

Background: The heterogeneous clinical presentation of graft microvascular inflammation poses a major challenge to successful kidney transplantation. The effect of microvascular inflammation on allograft outcomes is unclear.

Methods: We conducted a cohort study that included kidney-transplant recipients from more than 30 transplantation centers in Europe and North America who had undergone allograft biopsy between 2004 and 2023.

Archetypal Analysis of Kidney Allograft Biopsies Using Next-generation Sequencing Technology.

Background: In kidney transplantation, molecular diagnostics may be a valuable approach to improve the precision of the diagnosis. Using next-generation sequencing (NGS), we aimed to identify clinically relevant archetypes.

Methods: We conducted an Illumina bulk RNA sequencing on 770 kidney biopsies (540 kidney recipients) collected between 2006 and 2021 from 11 European centers.

Evaluation of non-invasive biomarkers of kidney allograft rejection in a prospective multicenter unselected cohort study (EU-TRAIN).

Non-invasive biomarkers are promising tools for improving kidney allograft rejection monitoring, but their clinical adoption requires more evidence in specifically designed studies. To address this unmet need, we designed the EU-TRAIN study, a large prospective multicentric unselected cohort funded by the European Commission. Here, we included consecutive adult patients who received a kidney allograft in nine European transplant centers between November 2018 and June 2020.

Long-Term Outcomes after Conversion to a Belatacept-Based Immunosuppression in Kidney Transplant Recipients.

Background: Conversion to a belatacept-based immunosuppression is currently used as a calcineurin inhibitor (CNI) avoidance strategy when the CNI-based standard-of-care immunosuppression is not tolerated after kidney transplantation. However, there is a lack of evidence on the long-term benefit and safety after conversion to belatacept.

Methods: We prospectively enrolled 311 kidney transplant recipients from 2007 to 2020 from two referral centers, converted from CNI to belatacept after transplant according to a prespecified protocol.

A Machine Learning-Driven Virtual Biopsy System For Kidney Transplant Patients.

In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters.

Identification of liver transplant biopsy phenotypes associated with distinct liver biological markers and allograft survival.

The intricate association between histologic lesions and circulating antihuman leucocyte antigen donor-specific antibodies (DSA) in liver transplantation (LT) requires further clarification. We conducted a probabilistic, unsupervised approach in a comprehensively well-annotated LT cohort to identify clinically relevant archetypes. We evaluated 490 pairs of LT biopsies with DSA testing from 325 recipients transplanted between 2010 and 2020 across 3 French centers and an external cohort of 202 biopsies from 128 recipients.

Prognostic Biomarkers in Kidney Transplantation: A Systematic Review and Critical Appraisal.

Significance Statement: Why are there so few biomarkers accepted by health authorities and implemented in clinical practice, despite the high and growing number of biomaker studies in medical research ? In this meta-epidemiological study, including 804 studies that were critically appraised by expert reviewers, the authors have identified all prognostic kidney transplant biomarkers and showed overall suboptimal study designs, methods, results, interpretation, reproducible research standards, and transparency. The authors also demonstrated for the first time that the limited number of studies challenged the added value of their candidate biomarkers against standard-of-care routine patient monitoring parameters. Most biomarker studies tended to be single-center, retrospective studies with a small number of patients and clinical events.

Complement-activating donor-specific anti-HLA antibodies in solid organ transplantation: systematic review, meta-analysis, and critical appraisal.

Introduction: Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.

Methods: We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants.

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.

Excess mortality after kidney transplantation: does sex matter?

Understanding sex differences in graft outcomes within the course of kidney transplantation is needed to unravel factors leading to the observed disparities and further improve patient management. In this issue, Vinson et al. presented a relative survival analysis comparing the excess risk of mortality in female and male recipients after kidney transplantation.

Sudden cardiac death after heart transplantation: a population-based study.

Aims: The epidemiology of sudden cardiac death (SCD) after heart transplantation (HTx) remains imprecisely described. We aimed to assess the incidence and determinants of SCD in a large cohort of HTx recipients, compared with the general population.

Methods And Results: Consecutive HTx recipients (n = 1246, 2 centres) transplanted between 2004 and 2016 were included.

An automated histological classification system for precision diagnostics of kidney allografts.

For three decades, the international Banff classification has been the gold standard for kidney allograft rejection diagnosis, but this system has become complex over time with the integration of multimodal data and rules, leading to misclassifications that can have deleterious therapeutic consequences for patients. To improve diagnosis, we developed a decision-support system, based on an algorithm covering all classification rules and diagnostic scenarios, that automatically assigns kidney allograft diagnoses. We then tested its ability to reclassify rejection diagnoses for adult and pediatric kidney transplant recipients in three international multicentric cohorts and two large prospective clinical trials, including 4,409 biopsies from 3,054 patients (62.

Machine learning does not outperform traditional statistical modelling for kidney allograft failure prediction.

Machine learning (ML) models have recently shown potential for predicting kidney allograft outcomes. However, their ability to outperform traditional approaches remains poorly investigated. Therefore, using large cohorts of kidney transplant recipients from 14 centers worldwide, we developed ML-based prediction models for kidney allograft survival and compared their prediction performances to those achieved by a validated Cox-Based Prognostication System (CBPS).

Comparison of artificial intelligence and human-based prediction and stratification of the risk of long-term kidney allograft failure.

Background: Clinical decisions are mainly driven by the ability of physicians to apply risk stratification to patients. However, this task is difficult as it requires complex integration of numerous parameters and is impacted by patient heterogeneity. We sought to evaluate the ability of transplant physicians to predict the risk of long-term allograft failure and compare them to a validated artificial intelligence (AI) prediction algorithm.

Progression of histological lesions after ABO incompatible kidney transplantation.

Recent large meta-analyses suggested a poorer long-term patients' and grafts' outcomes after ABO incompatible (ABOi) living-donor kidney transplantation (LDKT) compared to ABO compatible LDKT. However, little is known about the long-term histological pattern after ABOi LDKT. We compared the histological features observed on protocol biopsies from 03/11 to 11/19 in 94 ABOi LDKT (including 14 with preformed Donor Specific Antibodies, pDSAs), 27 LDKT ABO compatible (ABOc) with pDSAs, and 21 ABOc without pDSAs) during the first five years post transplantation.