Landscape of subclinical rejection in a large international cohort of pediatric kidney transplant (kTx) recipients.

Kidney allograft rejection occurs in clinically stable patients, but its long-term significance in children is unknown. Previous studies demonstrated that subclinical inflammation is associated with an increased risk of rejection. However, the prevalence and significance of subclinical antibody-mediated rejection and the impact of subclinical (SC) rejection phenotypes on graft survival remains to be assessed.

Maximum cold ischemia duration for a kidney allograft: a prediction model for allograft failure at the time of organ allocation.

Background: Many determinants of kidney allograft failure are established at the time of allocation by organ distribution agencies. At this point, the main modifiable factor is the duration of cold ischemia (CIT). Currently, no practical tool exists to determine the maximum permissible cold ischemia time for a specific recipient at allocation.

Impact of HLA evolutionary divergence and donor-recipient molecular mismatches on antibody-mediated rejection of kidney allografts.

Several in-silico methods emerge to assess HLA immunogenicity and stratify immunological risk, including HLA molecular mismatches and HLA evolutionary divergence (HED). However, their added value in risk-stratifying antibody-mediated rejection (AMR) remains uncertain. We include 5159 kidney transplant recipients from four centers.

Detection of Kidney Allograft Rejection Using Urinary Chemokines.

Background: Urinary chemokines CXCL9 and CXCL10 have shown promise for detecting kidney allograft rejection, but the demonstration of their added value beyond standard of care patient monitoring requires further study.

Methods: We prospectively enrolled adult patients who underwent kidney transplantation in 7 transplant referral centers between July 2018 and December 2019 (ClinicalTrials.gov, NCT03582436).

Molecular diagnosis of kidney allograft rejection based on the Banff Human Organ Transplant gene panel: A multicenter international study.

Transcriptomic analysis of kidney biopsies has demonstrated the potential to improve diagnosis of allograft rejection. Here, we developed a molecular assessment of antibody-mediated rejection (AMR) and T cell-mediated rejection (TCMR) based on the Banff Human Organ Transplant consensus gene panel. Expression assays of formalin-fixed paraffin-embedded kidney biopsies from well-phenotyped cohorts were used to develop prediction models for AMR and TCMR and an automated report of gene expression-based diagnosis.

Competing and Noncompeting Risk Models for Predicting Kidney Allograft Failure.

Background: Prognostic models are becoming increasingly relevant in clinical trials as potential surrogate end points and for patient management as clinical decision support tools. However, the effect of competing risks on model performance remains poorly investigated. We aimed to carefully assess the performance of competing risk and noncompeting risk models in the context of kidney transplantation, where allograft failure and death with a functioning graft are two competing outcomes.

Donor HLA-DQ genetic and functional divergence affect the control of BK polyoma virus infection after kidney transplantation.

BK polyomavirus (BKPyV) infection remains a major concern after kidney transplantation, increasing the risk of graft loss in the absence of specific antiviral agent now available. Here, we investigated the impact of HLA diversity on the control of posttransplant BKPyV replication. High HLA evolutionary divergence (HED) at the DQ locus in the donor was an independent predictor of BKPyV-free outcome.

BK Polyomavirus Infection in Kidney Transplantation: A Comprehensive Review of Current Challenges and Future Directions.

BK polyomavirus (BKPyV) infection of the kidney graft remains a major clinical issue in the field of organ transplantation. Risk factors for BKPyV-associated nephropathy (BKPyVAN) and molecular tools for determining viral DNA loads are now better defined. BKPyV DNAemia in plasma, in particular, plays a central role in diagnosing active infection and managing treatment decisions.

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.

Prospective comparison of cytomegalovirus quantification in whole blood and plasma samples among hematopoietic stem cell transplant and kidney transplant recipients.

Background: Cytomegalovirus (CMV) induces multi-organ pathogenesis in hematopoietic stem cell transplant (HSCT) and kidney transplant (KT) recipients. Effective management involves systematic monitoring for CMV reactivation by quantitative real-time PCR, allowing timely preemptive intervention. However, the optimal blood compartment for CMV surveillance remains undetermined.

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.

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.

Qualifying a novel clinical trial endpoint (iBOX) predictive of long-term kidney transplant outcomes.

New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute's Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency's qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials.

Validation of a prediction system for risk of kidney allograft failure in pediatric kidney transplant recipients: An international observational study.

Predicting long-term kidney allograft failure is an unmet need for clinical care and clinical trial optimization in children. We aimed to validate a kidney allograft failure risk prediction system in a large international cohort of pediatric kidney transplant recipients. Patients from 20 centers in Europe and the United States, transplanted between 2004 and 2017, were included.

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.

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.

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.

Outcomes in kidney transplant recipients treated with immediate-release tacrolimus capsules versus extended-release tacrolimus capsules: A cohort study.

Introduction: Prior randomized trials and observational studies have generally reported similar outcomes in kidney transplant recipients (KTRs) treated with immediate-release tacrolimus (IR-TAC) versus extended-release tacrolimus (ER-TAC). However, many of these previous studies focused on patients with low immunological risks, had small sample sizes and brief follow-up periods, and excluded outcomes associated with graft loss, such as chronic rejection.

Methods: To address these limitations, we conducted a cohort study of 848 KTRs at a single transplantation center who had generally high immunological risks and were treated with either IR-TAC capsules (589 patients, 65.

Cryptococcal Meningitis in Kidney Transplant Recipients: A Two-Decade Cohort Study in France.

Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France.