Donor-derived cell-free DNA monitoring for early diagnosis of antibody-mediated rejection after kidney transplantation: a randomized trial.

Background And Hypothesis: Donor-derived cell-free DNA (dd-cfDNA) shows good diagnostic performance for the detection of antibody-mediated rejection (AMR) in kidney transplant recipients (KTR). However, the clinical benefits of dd-cfDNA monitoring need to be established. Early diagnosis of AMR at potentially reversible stages may be increasingly important due to emerging treatment options for AMR.

Kidney transplantation in patients with polycystic kidney disease: increased risk of infection does not compromise graft and patient survival.

Background: Patients with autosomal dominant polycystic kidney disease (ADPKD) represent >10% of patients awaiting kidney transplantation. These patients are prone to potentially severe urinary tract (UTI) and liver cyst infections after transplantation. Whether such infections compromise outcome is unclear.

Opinions on the Future of Clinical Pig Kidney Xenotransplantation.

Based on promising results obtained in primate models, pioneers in the US have now started to explore the new frontier of genetically-edited pig-to-human transplantation. The recent transition of xenotransplantation into clinical medicine has included transplants in brain-dead subjects and the compassionate use of xenotransplants in living recipients without options for allotransplantation. While the barrier of hyperacute rejection seems to be successfully overcome by gene editing of donor pigs, the occurrence of accelerated rejection could pose significant limitations to the success of the procedure.

Continuous Glucose Monitoring for the Diagnosis of Post-Transplantation Diabetes Mellitus and Impaired Glucose Tolerance From Years One to Five After Kidney Transplantation-A Prospective Pilot Study.

Post-transplantation diabetes mellitus (PTDM) and prediabetes are associated with increased cardiovascular morbidity and mortality in kidney transplant recipients (KTR), when diagnosed by an oral glucose tolerance test (oGTT). Hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) display low concordance with the oGTT in the early phase posttransplant. For this prospective cross-sectional pilot study, 41 KTR from years one to five after transplantation without known preexisting PTDM (defined by HbA1c ≥ 6.

Mind the lag: understanding genetic extinction debt for conservation.

The delay between disturbance events and genetic responses within populations is a common but surprisingly overlooked phenomenon in ecology and evolutionary and conservation genetics. If not accounted for when interpreting genetic data, this time lag problem can lead to erroneous conservation assessments. We (i) identify life-history traits related to longevity and reproductive strategies as the main determinants of time lags, (ii) evaluate potential confounding factors affecting genetic parameters during time lags, and (iii) propose approaches that allow controlling for time lags.

European Association of Urology Guidelines on Renal Transplantation: Update 2024.

Background And Objective: The European Association of Urology (EAU) Panel on Renal Transplantation released an updated version of the renal transplantation (RT) guidelines. This report aims to present the 2024 EAU guidelines on RT.

Methods: A broad and comprehensive scoping exercise covering all areas of RT guidelines published between May 31, 2020 and April 1, 2023 was performed.

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.

Resilience of genetic diversity in forest trees over the Quaternary.

The effect of past environmental changes on the demography and genetic diversity of natural populations remains a contentious issue and has rarely been investigated across multiple, phylogenetically distant species. Here, we perform comparative population genomic analyses and demographic inferences for seven widely distributed and ecologically contrasting European forest tree species based on concerted sampling of 164 populations across their natural ranges. For all seven species, the effective population size, N, increased or remained stable over many glacial cycles and up to 15 million years in the most extreme cases.

Periodontitis adversely affects lipoprotein subfractions - results from the cohort study SHIP-TREND: Periodontitis adversely affects lipoprotein subfractions.

Aim: We aimed to investigate the medium-term associations of periodontitis and the number of missing teeth with serum lipoproteins and their plasma subfractions using follow-up data from the population-based Study of Health in Pomerania (SHIP-TREND).

Methods: A total of 2,058 participants with 7-year follow-up data underwent periodontal examinations, serum lipid panel tests, and proton nuclear magnetic resonance (H-NMR) spectroscopy of plasma lipoproteins and their subfractions. Generalized models with gamma distribution and loglink were used to analyze associations between periodontal variables and lipoproteins and their subfractions, adjusting for confounders using propensity score weighting.

Prospectively investigating the impact of AI onshared decision-making in post kidney transplant care (PRIMA-AI): protocol for a longitudinal qualitative study among patients, their support persons and treating physicians at a tertiary care centre.

Introduction: As healthcare is shifting from a paternalistic to a patient-centred approach, medical decision making becomes more collaborative involving patients, their support persons (SPs) and physicians. Implementing shared decision-making (SDM) into clinical practice can be challenging and becomes even more complex with the introduction of artificial intelligence (AI) as a potential actant in the communicative network. Although there is more empirical research on patients' and physicians' perceptions of AI, little is known about the impact of AI on SDM.

Deceased donor urinary Dickkopf-3 associates with future allograft function following kidney transplantation.

Predicting future kidney allograft function is challenging. Novel biomarkers, such as urinary Dickkopf-3 (uDKK3), may help guide donor selection and improve allograft outcomes. In this prospective multicenter pilot trial, we investigated whether donor uDKK3 reflects organ quality and is associated with future allograft function.

Synthetic cartilage implant vs. first metatarsophalangeal arthrodesis for the treatment of hallux rigidus.

Background: This study evaluated the outcome of the Cartiva synthetic cartilage implant (SCI) in the treatment of hallux rigidus.

Methods: In the present retrospective matched case-control study, we compared 18 patients with Cartiva SCI (mean follow-up: 17.7 months) to 18 patients with metatarsophalangeal joint arthrodesis (mean follow-up: 20 months) using multiple function measures, along with four specified visual analog subscales for pain.

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.

Chronic Rejection After Kidney Transplantation.

In kidney transplantation, ongoing alloimmune processes-commonly triggered by HLA incompatibilities-can trigger chronic transplant rejection, affecting the microcirculation and the tubulointerstitium. Continuous inflammation may lead to progressive, irreversible graft injury, culminating in graft dysfunction and accelerated transplant failure. Numerous experimental and translational studies have delineated a complex interplay of different immune mechanisms driving rejection, with antibody-mediated rejection (AMR) being an extensively studied rejection variant.

Perspective for Donor-Derived Cell-Free DNA in Antibody-Mediated Rejection After Kidney Transplantation: Defining Context of Use and Clinical Implications.

Antibody-mediated rejection (AMR) is a major cause of graft failure limiting long-term graft survival after kidney transplantation. Current diagnostic strategy to detect AMR is suboptimal and requires further improvement. Previously suggested treatment regimens for AMR could not demonstrate efficacy, however novel therapeutic agents are currently under investigation.

Continuous Insulin Therapy to Prevent Post-Transplant Diabetes Mellitus: A Randomized Controlled Trial.

Rationale & Objectives: Hyperglycemia is frequently observed early after transplantation and associated with development of post-transplant diabetes mellitus (PTDM). Here, we assessed continuous subcutaneous insulin infusion (CSII) targeting afternoon hyperglycemia.

Study Design: Open-label randomized parallel 3-arm design.

Donor-Derived Cell-Free DNA as a Companion Biomarker for AMR Treatment With Daratumumab: Case Series.

Antibody-mediated rejection (AMR) is among the most frequent causes for graft loss after kidney transplantation. While there are no approved therapies, several case reports with daratumumab and the very recent phase 2 trial of felzartamab in AMR have indicated the potential efficacy of therapeutic interventions targeting CD38. Donor-derived cell-free DNA (dd-cfDNA) is an emerging biomarker with injury-specific release and a short half-life, which could facilitate early diagnosis of AMR and monitoring of treatment response.

Risk Stratification Before Living Donor Kidney Transplantation in Patients With Preformed Donor-specific Antibodies by Different Crossmatch Methods.

Background: Preformed donor-specific HLA antibodies (DSA) are a well-known risk factor in kidney transplantation. There is still considerable debate, however, about the optimal risk stratification among patients with preformed DSA. Additionally, data on the prognostic value of different crossmatch assays in DSA-positive patients are scarce.

Long-Term Outcome after Early Mammalian Target of Rapamycin Inhibitor-Based Immunosuppression in Kidney Transplant Recipients.

The use of mammalian target of rapamycin inhibitors (mTORis) in kidney transplantation increases the risk of donor-specific human leukocyte antigen (HLA) antibody formation and rejection. Here, we investigated the long-term consequences of early mTORi treatment compared to calcineurin inhibitor (CNI) treatment. In this retrospective single-center analysis, key outcome parameters were compared between patients participating in randomized controlled immunosuppression trials between 1998 and 2011, with complete follow-up until 2018.