Highly sensitized kidney recipients

BACKGROUND: Recent advances in hardware and software enabled the use of artificial intelligence (AI) algorithms for analysis of complex data in a wide range of daily-life use cases. We aim to explore the benefits of applying AI to a specific use case in transplant nephrology: risk prediction for severe posttransplant events. For the first time, we combine multinational real-world transplant data, which require specific legal and technical protection measures. OBJECTIVE: The German-Canadian NephroCAGE consortium aims to develop and evaluate specific processes, software tools, and methods to (1) combine transplant data of more than 8000 cases over the past decades from leading transplant centers in Germany and Canada, (2) implement specific measures to protect sensitive transplant data, and (3) use multinational data as a foundation for developing high-quality prognostic AI models...

INTRODUCTION: Kidney transplant recipients (KTRs) have an increased risk of cardiovascular (CV) events (CVEs) compared with the general population. The impact of insulin resistance on CV risk after transplantation is not well defined. METHODS: We tested whether triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, may predict posttransplant CVEs in a cohort of 715 consecutive KTRs all included 1 year after transplant. RESULTS: Follow-up was 9...

BACKGROUND: In 2015, the Spanish National Transplant Organization developed a prioritization system (Program for Access to Transplantation for Highly Sensitized Patients [PATHI]) to increase transplant options for patients with calculated panel-reactive antibodies (cPRAs) ≥98%, based on virtual crossmatch. We describe the experience with the implementation of PATHI and assess its efficacy. METHODS: PATHI registry was used to collect characteristics of donors and patients between June 15, 2015, and March 1, 2018...

INTRODUCTION: Polyomavirus (BKV) infection can lead to major complications and damage to the graft in kidney transplant recipients (KTRs). We investigated whether pretransplant BK serostatus and BK-specific cell-mediated immunity (CMI) predicts post-transplant BK infection. METHODS: A total of 93 donor-recipient pairs who underwent kidney transplantation (KT) and 44 healthy controls were examined. Assessment of donor and recipient BKV serostatus and BKV-CMI in recipients was performed prior to transplantation using BKV-IgG ELISA and BKV-specific IFN-g ELISPOT assays against five BK viral antigens (LT, St, VP1, VP2, and VP3)...

BACKGROUND: Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic review aims to reevaluate, based on actual studies, the effects of different antibody preparations when used in specific KTR subgroups. METHODS: We searched MEDLINE and CENTRAL and selected randomized controlled trials (RCT) and observational studies looking at different antibody preparations used as induction in KTR...

With increasing knowledge of immunologic factors and with the advent of potent immunosuppressive agents, the last several decades have seen significantly improved kidney allograft survival. However, despite overall improved short to medium-term allograft survival, long-term allograft outcomes remain unsatisfactory. A large body of literature implicates acute and chronic rejection as independent risk factors for graft loss. In this article, we review measures taken at various stages in the kidney transplant process to minimize the risk of rejection...

BACKGROUND: Incomplete resolution of T cell-mediated rejection (TCMR) after treatment may not be detected with serum creatinine monitoring and is associated with donor-specific antibodies and chronic rejection. We evaluate the utility of follow-up biopsies (FUB) to identify and characterize rates of persistent TCMR after treatment in pediatric kidney transplant patients. METHODS: Patients from two pediatric transplant centers performing standard of care FUB at 1...

Kidney paired donation (KPD) is a major innovation that is changing the landscape of kidney transplantation in the United States. We used the 2006-2021 United Network for Organ Sharing data to examine trends over time. KPD is increasing, with 1 in 5 living donor kidney transplants (LDKTs) in 2021 facilitated by KPD. The proportion of LDKT performed via KPD was comparable for non-Whites and Whites. An increasing proportion of KPD transplants are going to non-Whites. End-chain recipients are not identified in the database...

"In solid organ transplantation, the compatibility between recipient and donor relies on testing prior to transplantation as a major determinant for the successful transplant outcomes. This compatibility testing depends on the detection of donor-specific antibodies (DSAs) present in the recipient. Indeed, sensitized transplant candidates are at higher risk of allograft rejection and graft loss compared to non-sensitized individuals. Most of the laboratories in India have adopted test algorithms for the appropriate risk stratification of transplants, namely: 1) donor cell-based flow-cytometric cross-match (FCXM) assay with patient's serum to detect DSAs; 2) HLA-coated beads to detect anti-HLA antibodies; and 3) complement-dependent cytotoxicity crossmatch (CDCXM) with donor cells to detect cytotoxic antibodies...

PURPOSE: The aim of this study was to quantify renal microcirculatory perfusion in braindead donors using contrast-enhanced ultrasonography (CEUS), and to establish an accurate, noninvasive, and convenient index for predicting delayed graft function (DGF) post-transplantation. METHODS: In total, 90 brain-dead donor kidneys (training group, n=60; validation group, n=30) examined between August 2020 and November 2022 were recruited in this prospective study. CEUS was performed on the kidneys of brain-dead donors 24 hours before organ procurement and time-intensity curves were constructed...

BACKGROUND: A potential contributor to fatigue in kidney transplant recipients (KTR) may be impaired creatine homeostasis. We developed and validated a high-throughput NMR assay allowing for simultaneous measurement of circulating creatine and creatinine, and determined plasma creatine and estimated intramuscular creatine concentrations in KTRs, delineated their determinants and explored their associations with self-reported fatigue. METHODS: An NMR assay was developed and validated for measurement of circulating creatinine and creatine...

INTRODUCTION: Previous research demonstrated benefits of late conversion to mTOR inhibitors against cutaneous squamous cell carcinomas (cSCC) in kidney transplant recipients (KTR), despite of poor tolerability. This study investigated whether stepwise conversion to sirolimus monotherapy without an attack dose modified the course of disease with improved tolerability. METHODS: This prospective exploratory study included non-sensitized KTR with more than 12-months post-transplant, on continuous use of calcineurin inhibitors (CNI)-based therapy, and with poor-prognosis cSCC lesions...

Decoy cells that can be detected in the urine sediment of immunosuppressed patients are often caused by the uncontrolled replication of polyomaviruses, such as BK-Virus (BKV) and John Cunningham (JC)-Virus (JCV), within the upper urinary tract. Due to the wide availability of highly sensitive BKV and JCV PCR, the diagnostic utility of screening for decoy cells in urine as an indicator of polyomavirus-associated nephropathy (PyVAN) has been questioned by some institutions. We hypothesize that specific staining of different infection time-dependent BKV-specific antigens in urine sediment could allow cell-specific mapping of antigen expression during decoy cell development...

RATIONALE AND OBJECTIVE: The incidence of kidney disease is high in patients after allogeneic hematopoietic cell transplantation (aHCT). Although rarely performed, kidney biopsy may be useful to make a precise diagnosis because several mechanisms and risk factors can be involved, and to adjust the treatment accordingly. This case series aimed to report the spectrum of biopsy findings from patients with kidney injury after aHCT. STUDY DESIGN: Single-center retrospective case series...

OBJECTIVE: Our objective was to identify consistent predictors of multiple adverse outcomes of adult deceased donor (DD) kidney transplant recipients (KTRs) of varying sensitization status. METHODS: We used the national transplant database in studying 62037 adult DD-KTRs between Dec. 2007 and Jun. 2015 stratified into sensitization cohorts based on calculated panel reactive antibody (CPRA) of <10%, 10%-79%, and ≥80%. We used multivariable logistic regressions for the analysis of risks for delayed graft function (DGF), and of acute rejection (AR) and hospitalization in the first year of transplant, and Cox hazard regression for 5-year overall graft loss (OAGL) and death...

The complement system is paramount in the clearance of pathogens and cell debris, yet is increasingly recognized as a key component in several pathways leading to allograft injury. There is thus a growing interest in new biomarkers to assess complement activation and guide tailored therapies after kidney transplantation (KTx). C5 blockade has revolutionized post-transplant management of atypical hemolytic uremic syndrome, a paradigm of complement-driven disease. Similarly, new drugs targeting the complement amplification loop hold much promise in the treatment and prevention of recurrence of C3 glomerulopathy...

RATIONALE & OBJECTIVE: Vitamin D is widely used to manage chronic kidney disease-mineral and bone disorder (CKD-MBD). We evaluated the effects of vitamin D therapy on mortality, cardiovascular, bone, and kidney outcomes in adults with CKD. STUDY DESIGN: Systematic review of randomized controlled trials (RCT) with highly sensitive searching of MEDLINE, Embase, and CENTRAL, through February 25, 2023. SETTING & STUDY POPULATIONS: Adults with stage 3, 4, or 5 CKD, including kidney failure treated with dialysis...

UNLABELLED: Presensitized patients awaiting a kidney transplant have a lower graft survival and a longer waiting time because of the limited number of potential donors and the higher risk of antibody-mediated rejection (AMR), particularly in the early posttransplant period, because of preformed donor-specific antibodies binding major histocompatibility complex (MHC) molecules expressed by the graft endothelium followed by the activation of the complement. Advances in kidney preservation techniques allow the development of ex vivo treatment of transplants...

Objective: To investigate the prevalence of frailty among kidney transplant recipients and to analyze the influential factors of frailty after kidney transplantation. Methods: We retrospectively included 201 kidney transplant recipients who were followed up in the Department of Urology, Beijing Chao-yang Hospital, Capital Medical University from November 2020 to May 2022. We investigated the prevalence of frailty based on the Fried Frailty Scale (including unexpected shrinking, slow walking speed, poor grip strength, low physical activity, and exhaustion)...

Background and Objectives : The aim of our study was to categorize very highly sensitized kidney transplant recipients with pre-transplant panel reactive antibody (PRA) ≥ 98% using an unsupervised machine learning approach as clinical outcomes for this population are inferior, despite receiving increased allocation priority. Identifying subgroups with higher risks for inferior outcomes is essential to guide individualized management strategies for these vulnerable recipients. Materials and Methods : To achieve this, we analyzed the Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) database from 2010 to 2019 and performed consensus cluster analysis based on the recipient-, donor-, and transplant-related characteristics in 7458 kidney transplant patients with pre-transplant PRA ≥ 98%...