Transplant Care Research Articles

Standardizing health outcomes for chronic kidney disease. Adaptation of the international consortium for health outcomes measurement standard set to the Spanish setting

Background and objectivesWe aim to adapt the International Consortium for Health Outcomes Measurements standard set for chronic kidney disease (CKD) patients to the Spanish setting and supplement it with those variables agreed upon through initiatives proposed by the Spanish Society of Nephrologists (S.E.N.). Material and methodsThe working group defined a first standard set of variables based on a literature review. The S.E.N. members then assessed the suitability of each variable for inclusion (Consensus≥75%). A second draft of the standard set was generated and evaluated by the Patient advocacy group Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón (ALCER). Lastly, the working group established the final standard set of variables (Consensus≥75%). ResultsThe standard set targets patients with very high-risk CKD (G3a/A3 and G3b/A2-G5) in pre-end-stage kidney disease (pre-ESKD), hemodialysis (HD), peritoneal dialysis (PD), kidney transplantation (KT) or conservative care (CC). The essential follow-up variables agreed for all patients (All) were patient survival, hospitalizations, cardiovascular events, smoking status, health-related quality of life, pain, fatigue, physical function, daily activities, depression, renal function and hemoglobin. Additionally, it was agreed to collect PD survival (in PD patients), peritonitis (PD), infection/bacteremia (PD, HD, KT), vascular access type (HD), vascular access survival (HD), acute rejection (KT), post-transplant cancer (KT), albuminuria (KT) and kidney allograft survival (KT). The optional variables agreed were phosphorus (All), potassium (All), diabetes control (All with diabetes), and albuminuria (pre-ESKD). ConclusionsThis standard set may constitute a highly efficient tool allowing the evaluation of patient outcomes and helping to define strategies to enhance CKD patients’ quality of care in the Spanish healthcare system.

Optimizing Intraoperative Haemodynamics and Haemostasis to Enhance Recovery After Liver Transplantation for Cirrhosis in Adults

Cirrhosis with end stage liver disease is a leading cause of non-communicable disease related deaths in Sri Lanka. Liver transplantation remains the only curative treatment for such patients. Multi-organ dysfunction characteristic of end stage liver disease, surgical and anaesthetic factors, quality of the graft, coagulopathy and haemodynamic instability, all lead to the complexity of the perioperative care for liver transplant. Aggressive management focused particularly on maintaining intra-operative haemodynamic stability and optimizing haemostasis, directly impacts successful patient outcomes and forms the core of the anaesthetic strategy.

Immune checkpoint inhibitors for solid organ transplant recipients: clinical updates.

Transplant care continues to advance with increasing clinical experience and improvements in immunosuppressive therapy. As the population ages and long-term survival improves, transplant patient care has become more complex due to comorbidities, frailty, and the increased prevalence of cancer posttransplantation. Immune checkpoint inhibitors (ICIs) have become a standard treatment option for many cancers in non-transplant patients, but the use of ICIs in transplant patients is challenging due to the possibility of disrupting immune tolerance. However, over the past few years, ICIs have gradually started to be used in transplant patients as well. In this study, we review the current use of ICIs after all solid organ transplantation procedures (kidney, liver, heart, and lung). Increasing data suggest that the type and number of immunosuppressants may affect the risk of rejection after immunotherapy. Immunotherapy for cancer in transplant patients may be a feasible option for selected patients; however, prospective trials in specific organ transplant recipients are needed.

Simulation in Perioperative Liver Transplant Anesthesia: A Systematic Review.

Due to the complexity of liver transplant patients and the variability in exposure to transplantation by anesthesia trainees, simulation is often required as an adjunct to clinical experience. This systematic review identifies current simulation models in the literature that pertain to perioperative liver transplant anesthesia.Data were collected by performing an electronic search of the PubMed and Scopus databases for articles describing simulation in transplant anesthesia. s were screened using the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Three reviewers analyzed 16 abstracts found in the search and agreed upon articles that met the inclusion criteria for the systematic review.A total of five publications met the inclusion criteria; they could be grouped as cognitive skills and technical skills simulators. Cognitive skills simulators utilized high-fidelity mannequins and animal models combined with traditional educational material to enhance pattern recognition of critical complications during liver transplantation. One manuscript focused on a technical skills acquisition by utilizing transesophageal echocardiography (TEE) to identify intraoperative pathologies.There is a heterogeneity in the exposure to liver transplant care during anesthesia training. Simulation provides low-stakes exposure to the high-stakes skills required in the operating room. Hence, it can be used as an adjunct to improve both cognitive and technical skill acquisition for perioperative transplant anesthesia. The goal of these simulation programs is to improve patient outcomes and produce more capable anesthesiologists.

Managing the Transition from Patient-Centered Care to Protocol.

Managing the Transition from Patient-Centered Care to Protocol David Slakter I learned that I would need a kidney transplant in the summer of 2015. This was not a complete surprise to me, as I had been subjected to a number of tests and invasive procedures to investigate nephritis since I was a child. I had heard similar stories of clinicians performing repeated tests on my father for similar reasons without any conclusions. Following my recommendation for transplant and consultation with genomics specialists, the cause of my kidney failure was determined to be Alport syndrome. What made Alport syndrome so difficult to diagnose in my case was that the associated mutation is a rare, autosomal-dominant one that has only recently been associated with the condition. After reviewing the data on survival rates for transitioning to dialysis versus a transplant, my family and I then considered the success rates for living versus cadaver donors, and the success rates at various transplant centers. The current data favor the long-term outcomes of transplant over dialysis and living over cadaver donors. Since we had decided to focus on searching for a live donor, my nephrologist recommended contacting Renewal, an organization that specializes in connecting those in need of a kidney transplant with live donors and providing support for donors to make the donation process less burdensome. On Renewal’s recommendation, my family and friends reached out across their social networks to search for potential donors. Many of those tested for compatibility were eliminated on basic matching criteria, others due to previously undiagnosed medical problems. Finally, the wife of a childhood friend came forward as an eligible donor and was also an incredibly close match on the antigens tested for kidney transplants. Having a living donor who was also a friend made the transplant experience somewhat less intimidating than it might have been. It meant the transformation of an existing relationship with someone already close to me, with fewer open questions about what may have motivated them to be so generous than if the donor had been someone I did not know. It also meant our families could be together in the waiting room, and that we shared in each other’s recoveries. Life post-transplant has been a significant improvement from what it was like immediately beforehand. Before my transplant, I regularly weighed food and consulted nutrition charts to gauge how much potassium I was consuming. To prevent too much potassium from building up in my bloodstream, I had to take sodium polystyrene [End Page 111] regularly. As one might guess from the name, it tastes much like burnt Styrofoam, and I could only ingest it with copious amounts of fruit-flavored syrup (strawberry covered up the awful flavor the best). There are other potassium binders on the market now, so fewer people with kidney failure will likely need to engage in such gustatory experimentation. I was also able to engage in more activities than what was possible even years before my transplant. I had long experienced difficulty with aerobic exercises, but assumed the reason was merely being out of shape. Though I have always walked regularly, even the one-mile walk from my office to my apartment had become a chore by the end. Within a few months after my transplant, I was riding a bicycle all over NYC, from Harlem to Brooklyn and back regularly, and hiking trails in nearby state parks. I began sessions with a personal trainer and attained a level of fitness I had not reached since I played soccer as a child. The transition from personalized care to one more driven by protocol has been a surprising and challenging aspect of the transplant process. While my previous experience with medical treatment has been individual meetings with physicians, my post-transplant care is managed by a team of nephrologists and other specialists in transplant care. My initial transplant nephrologist was automatically assigned to me. Because the standard of care for transplant patients is often driven by protocol, my assigned nephrologist recommended a biopsy on my transplanted kidney due to results in my recent lab tests. When pressed on the necessity of a biopsy in my case versus...

Development of clinical pharmacy programs integrated into patient care pathways using adverse event risks.

In the strained actual economic context, all clinical pharmacy activities cannot be achieved for all patients of all care pathways. So finding a way to prioritize moments and patients needing those activities is essential. This is the challenge of the "5P project" (Patient personalized clinical pharmacy program integrated into care pathway). To present adverse event (AE) risk management approach applied to develop clinical pharmacy programs integrated into care pathway, using two methods. Used as a priori AE risk management approach, the Delphi method and inductive approach analysis of semi-directed interviews were realized from April 1st to October 3rd, 2019, respectively in orthogeriatric (OG) and pediatric kidney transplantation (PKT) care pathways. Complementarily to bibliographic research, participants were medical and paramedical healthcare providers involved in the concerned care pathway. They have been interrogated regarding AE risks to identify the clinical pharmacy activities required, the patients who need them, and the appropriate steps of the care pathway. The Delphi method for OG care pathway has revealed: 1/. Patients were prioritized by the presence of at least 2 among the following 4 criteria: age ≥90 years old, cardiovascular diseases, prescribed potentially inappropriate medication for elderly patients, obesity or diabetes; priority steps were the post-operative and rehabilitation care steps. 2/. Prescription reviews, medication reconciliation and targeted pharmaceutical informative interview about oral anticoagulants were required. Nine semi-directed interviews used for PKT care pathway has revealed: 1/. Clinical pharmacy activities were carried out for all patients. Priority steps were pre-transplantation, immediate post-operative, and post-transplantation. 2/. Prescription reviews and educative interviews were required. The two presented methods can be used to both develop patient prioritization and targeting steps for clinical pharmacy activities, and integrate it into care pathway. Today, those two developed programs have been executed in our teaching hospital.

Ways of improving the legal regulation of human organ and tissue transplantation in the Russian Federation

Over the past 10 years, significant breakthroughs have been achieved in Russian transplantology in the field of regulatory legal framework. During this period, the powers of government authorities in the field of healthcare on organization of transplant care and organ donation have been defined, and sources and mechanisms for target financing of medical activities related to organ donation for transplantation purposes have been identified. The procedure for providing medical care under surgery (human organ and/or tissue transplantation) has been adopted, and a state registry system for donor organs, donors and recipients has been created. Measures on organ donation and transplantation in the Russian Federation have been approved within the «Healthcare Development», a framework of the state program of the Russian Federation. The Shumakov National Medical Research Center of Transplantology and Artificial Organs (Shumakov Center) has also been identified as the core institution that coordinates the activities of the entire transplant industry in the Russian Federation. Transplant medical care is currently being provided by specialist physicians trained in human organ and tissue transplantation, in collaboration with other specialist physicians. The Nomenclature of Specialties of Specialists with Higher Medical and Pharmaceutical Education, approved by the Russian Ministry of Health via Order No. 700n of October 7, 2015, does not contain a separate specialty related to human organ and tissue transplantation activities, and this is quite justified. However, in order to improve the legal regulation of transplantation activities, it is necessary to unify the requirements for specialists providing medical care in human organ/tissue transplantation. This can be achieved by developing uniform approaches to the definition of labor functions in the professional standards of specialist doctors involved in transplantation.

Kidney donor profile index and post-transplant health care utilization: Implications for value of transplant care delivery.

Centers discard high kidney donor profile index (KDPI) allografts, potentially related to delayed graft function and prolonged hospital use by kidney transplant recipients (KTR). We sought to determine whether high KDPI KTRs have excess health care utilization. We conducted a retrospective cohort study from a high-volume center analyzing KTRs from January 3, 2011 to April 12, 2015 (n=652). We measured differences in hospital use, emergency visits, and outpatient visits within the first 90 days between low (≤85%) versus high KDPI (>85%) KTRs, as well as long-term graft function and patient survival. High (n=107) and low KDPI (n=545) KTRs had similar length of stay (median = 3 days, P=.66), and readmission rates at 7, 30, and 90 days after surgery (all, P>.05). High KDPI kidneys were not associated with excess utilization of the hospital, emergency services, outpatient transplant clinics, or ambulatory infusion visits on univariate or multivariate analysis (all, P>.05). Low KDPI KTRs had significantly better eGFR at 2years (Low vs. High KDPI: 60.35 vs. 41.54 ml/min, P<.001), but similar 3-year patient and graft survival (both, P>.09). High and low KDPI KTRs demonstrated similar 90-day risk-adjusted health care utilization, which should encourage use of high KDPI kidneys.

Cystic fibrosis and alpha-1 antitrypsin deficiency: case report and review of literature

BackgroundThis case report describes a child born with both cystic fibrosis (CF) and alpha-1 antitrypsin deficiency (A1ATD). Both are autosomal recessive inherited diseases, mainly affecting the lungs and the liver. The combination of both diseases together is rare and may lead to a fulminant disease with limited life span. To the best of our knowledge, no case has been reported of a patient born with both diseases.Case presentationAfter an uneventful pregnancy, a male baby was born with meconium ileus. The suspected diagnosis of CF was confirmed based on the sweat test and genetic analysis. The child developed persisting cholestasis, too severe to be likely caused by CF alone and indicating an associated problem. The diagnosis of A1ATD was established based on clinical suspicion (persisting cholestasis), decreased serum alpha-1 antitrypsin and genetic analysis. Supportive therapy was started, however the boy evolved to rapidly progressive liver disease leading to liver failure which necessitated an infant liver transplantation.ConclusionsThis case illustrates the complexity of care in case of two severe inherited diseases as well as post solid organ transplant care.

Attitudes Toward and Knowledge of Brain Death and Deceased Organ Donation Among Anesthesiologists in the Northeastern Region of Poland

Because in Poland transplant of organs from deceased donors is the predominant form of transplant, anesthesiology and intensive care specialists play a key role in the process. Insight into the work organization in intensive care units, anesthesiologists' and intensivists' level of knowledge and expertise, as well as personal opinions regarding declaring brain death and critical care of potential donors may be helpful in increasing transplant rates. The objective of this survey was to identify factors and challenges influencing donation rates in intensive care units of hospitals of various reference levels in region. An anonymous, 31-question survey was sent to anesthesiology and intensive care specialists working in hospitals in one of the regions of eastern Poland. The survey was completed by 133 physicians, and a quantitative analysis was conducted on the data collected from submitted answers. The average age of responders was 46 years (±10.24 years). Anesthesiology and intensive care specialists made up 80.45% of respondents. A vast majority of respondents (97%) expressed positive attitude toward transplant and are willing to donate their organs after death (92.19%). Meanwhile, more than 50% of them admit their lack of sufficient knowledge when it comes to declaring brain death. More than 53% of surveyed physicians have never had the opportunity to participate in training in methodology in performing brain death provided by their hospital or know about such training taking place. A vast majority of respondents (94.76%) see the need for workshops in potential organ donor care and brain death determination and would like to attend them. This study shows a positive outlook toward organ donation and transplant but at the same time reveals a lack of knowledge and expertise among doctors working in intensive care units. That is why implementing education tools for identification, declaration, and maintenance of brain-dead donors could be one of the keys to enhancing donation.

Technologies During the COVID-19 Pandemic: Teleconsultation in Care Management for Patients Undergoing Liver Transplant

BackgroundThe aim of this study was to identify home care management strategies for patients undergoing liver transplant, through teleconsultation, during the COVID-19 pandemic for maintenance and improvements in treatment adherence.MethodsThis was a qualitative, exploratory, and descriptive research study. Participants included patients who underwent liver transplant between 2020 and 2021. Through a semistructured script, data were analyzed according to the recommendations of content analysis and then simple statistics were applied.ResultsTwenty-two people participated in the study. Two analysis categories were developed, which resulted in 7 strategies and 22 care actions. The care strategy with the highest adherence involved actions related to the prevention of COVID-19.ConclusionsTeleconsultation is an excellent tool to manage and supervise post–liver transplant care of patients. Considering that teleconsultation has presented strategies and care actions, which were developed by the patients, the patients have a direct effect on treatment adherence despite pandemic impositions.

Use of Donor Derived Cell Free DNA for Long Term Rejection Surveillance in OHT Recipients

IntroductionThe advent of donor-derived cell free DNA (dd cf DNA) testing has transformed care for orthotopic heart transplant (OHT) recipients by reducing the number of invasive endomyocardial biopsies (EMB) for surveillance of acute rejection (AR). The dd cf DNA is elevated in any form of graft injury ranging from AR to ischemic injury from cardiac allograft vasculopathy (CAV). When used in combination with gene expression profiling, the AUC for the combination to rule out acute rejection is about 80.1% However, all the data about using dd cf DNA for AR surveillance is from studies done in the first few years after OHT. There is no data or recommendation on using dd cf DNA in long-term OHT survivors (>5 years). Here we present an interesting case of acute rejection detected by dd cf DNA in a patient who is 8 years post OHT.Case Report55 yo African American male with a history of OHT for non ischemic cardiomyopathy in 2013. He had no previous history of AR or CAV. As part of his routine post-transplant annual work-up, dd cf DNA was checked and it came back elevated at 0.95 % (Ref: >0.25% - significantly elevated, >1% - high probability of AR). Donor specific antibodies were negative. Echocardiogram revealed an ejection fraction of 55-60%. He had a right heart catheterization, which showed normal to low filling pressures and preserved cardiac index. EMB revealed Grade 1R cellular rejection as well as swollen endothelial cells, and >50% capillary positive staining with C4d consistent with acute antibody-mediated rejection (pAMR2). He was successfully treated with plasmapheresis/IVIG x 5 cycles and Rituximab. On further probing, the patient admitted to missing a few doses of his immunosuppression (IS) medications.SummaryThis case highlights the successful use of dd cf DNA for allograft rejection surveillance several years (>5 years) after OHT. However, there is sparse data in this population. Further studies are needed in large patient groups to assess the validity and reproducibility of dd cf DNA in long-term surveillance of rejection. The advent of donor-derived cell free DNA (dd cf DNA) testing has transformed care for orthotopic heart transplant (OHT) recipients by reducing the number of invasive endomyocardial biopsies (EMB) for surveillance of acute rejection (AR). The dd cf DNA is elevated in any form of graft injury ranging from AR to ischemic injury from cardiac allograft vasculopathy (CAV). When used in combination with gene expression profiling, the AUC for the combination to rule out acute rejection is about 80.1% However, all the data about using dd cf DNA for AR surveillance is from studies done in the first few years after OHT. There is no data or recommendation on using dd cf DNA in long-term OHT survivors (>5 years). Here we present an interesting case of acute rejection detected by dd cf DNA in a patient who is 8 years post OHT. 55 yo African American male with a history of OHT for non ischemic cardiomyopathy in 2013. He had no previous history of AR or CAV. As part of his routine post-transplant annual work-up, dd cf DNA was checked and it came back elevated at 0.95 % (Ref: >0.25% - significantly elevated, >1% - high probability of AR). Donor specific antibodies were negative. Echocardiogram revealed an ejection fraction of 55-60%. He had a right heart catheterization, which showed normal to low filling pressures and preserved cardiac index. EMB revealed Grade 1R cellular rejection as well as swollen endothelial cells, and >50% capillary positive staining with C4d consistent with acute antibody-mediated rejection (pAMR2). He was successfully treated with plasmapheresis/IVIG x 5 cycles and Rituximab. On further probing, the patient admitted to missing a few doses of his immunosuppression (IS) medications. This case highlights the successful use of dd cf DNA for allograft rejection surveillance several years (>5 years) after OHT. However, there is sparse data in this population. Further studies are needed in large patient groups to assess the validity and reproducibility of dd cf DNA in long-term surveillance of rejection.

Don't Take Another Piece of My Heart: Substantial Reduction in Biopsies with Initiation of Non-Invasive Rejection Surveillance at One Month Post-Transplant

<h3>Purpose</h3> Historically, the standard of care for post heart transplant (HT) rejection surveillance has been endomyocardial biopsies (EMB), with the majority of biopsies in the first 6 months. <h3>Methods</h3> This was a retrospective analysis of adult HT recipients from 1/2018 to 12/2020 at a single institution. All patients without multiorgan transplants were considered for non-invasive monitoring starting at 28 days. Patients were excluded from analysis if they died within 55 days post HT or moved to another transplant center within first year post transplant. Patients were analyzed in six month cohorts based on transplant date. The primary outcomes were the number of EMB performed in first six months and one year survival. <h3>Results</h3> A total of 106 HT recipients were included and divided into six cohorts. Distribution of biopsies by cohort is shown in Figure 1. Patients in later cohorts had fewer EMB in the first six months post transplant compared to those at the initiation of protocol (p<0.01). The July 2018 and July 2019 cohorts each had two patients expire, making their one year survival 88% and 87% respectively. All other cohorts had 100% survival. There was no difference in one year survival between cohorts (p=0.07) (Figure 2). Baseline characteristics, immunosuppression and use of induction was similar between groups. <h3>Conclusion</h3> Initiation of non-invasive rejection at surveillance at 28 days post-transplant significantly reduces the number of biopsies and results in similar 1 year survival As providers increasingly use non-invasive monitoring, the number of early EMB continue to decline.

Metagenomic Next Generation Sequencing (mNGS) Can Complement Fractional Donor-Derived Cell-Free DNA in Lung Allograft Assessment: Pilot Data

<h3>Purpose</h3> Transbronchial biopsy (TBBx) histology and lavage (BAL) for microbiology are standard of care in lung transplant (LT) evaluation, but are inherently flawed. Plasma donor-derived cell-free DNA (dd-cfDNA) and viral DNA/RNA (vDNA/RNA) are promising biomarkers for more accurate assessment of allograft injury. Here we compare TBBx histology, BAL microbiology, dd-cfDNA and vDNA/RNA in matched samples. <h3>Methods</h3> 40 post-LT samples (median 212 days) from 33 patients (median age: 61.0 yrs) were analyzed for dd-cfDNA fraction (Prospera™, Natera) and vDNA/RNA by metagenomic next-generation sequencing (mNGS) (Galileo™-ONE ArcBio) and correlated with clinical-pathologic (TBBx) diagnosis and BAL microbiology including Respiratory Viral Panel (RVP) multiplex PCR testing (BioFire RP2.1™; Biomerieux) <h3>Results</h3> Native lung diseases included: IPF (N=18), COPD (N=17), CF (N=2) and PAH (N=3). mNGS identified vDNA/RNA considered pathologic to LT in 27.5% (11/40) cases, including 2 previously undiagnosed cases of HIV-1, with a median dd-cfDNA of 1.14% [<b>TABLE</b>]. For 9 cases with "negative" BAL/RVP, putative respiratory viral infection was indicated by mNGS. vDNA/RNA was also detected in 3 cases of histologic acute cellular rejection (ACR), one of which had elevated dd-cfDNA. In 2/4 patients with chronic lung allograft dysfunction (CLAD), the dd-cfDNA fraction was elevated and associated with vDNA/RNA. Two stable patients (A0B0/X) with vDNA/RNA had elevated dd-cfDNA. <h3>Conclusion</h3> Detection of clinically significant vDNA/RNA signatures by plasma mNGS testing contradicted clinical-pathologic diagnoses in >25% of patients. Future studies will help better understand and adjudicate discrepant results between TBBx histology, BAL microbiology, dd-cfDNA and mNGS. mNGS testing offers promise for properly assigning clinical-pathologic diagnosis in the assessment of LT health and may support the appropriate adjudication of elevated dd-cfDNA fractions.

Donor-Derived Cell-Free DNA Plus Tissue Gene Expression Profiling of Lung Allograft Injury

<h3>Purpose</h3> Lung transplantation outcomes are limited by chronic lung allograft dysfunction, of which acute rejection is a significant risk factor. Acute rejection includes acute cellular rejection (ACR) and antibody-mediated rejection (AMR), and historically has been diagnosed through a combination of transbronchial biopsy histopathology, pulmonary function testing, and the presence of serum donor-specific antibodies. Donor-derived cell-free DNA (dd-cfDNA) has recently shown promise as a less invasive biomarker of allograft injury, but, in isolation, dd-cfDNA does not sufficiently delineate ACR from AMR from infection. Here we propose to combine dd-cfDNA analysis of allograft injury with in situ lung tissue gene expression to better characterize different forms of allograft injury following lung transplantation. <h3>Methods</h3> This is a single center retrospective cohort study of at least 20 lung transplant recipients with longitudinally matched plasma and transbronchial biopsies (n=100). All samples have previously been collected and stored. Plasma will be obtained from the institution's Total Transplant Care Protocol (TTCP) Biorepository, while formalin fixed paraffin embedded (FFPE) biopsy specimens will be obtained from the Department of Pathology through the institution's Tissue Archive Service (TAS). Samples will be assigned to specific clinical cohorts based on histopathology, radiology, microbiological studies and pulmonary function tests at the time of sample collection. Plasma dd-cfDNA fractions will be quantified using Allosure Lung (CareDx), and tissue gene expression profiles (GEP) will be captured with the nCounter Gene Expression Assay (Nanostring Technologies). Data will be analyzed with non-parametric tests and multivariate analyses to determine associations between dd-cfDNA levels and tissue gene expression patterns. <h3>Endpoints</h3> 1. Correlate plasma dd-cfDNA levels with acute allograft injury from ACR, AMR, or infection and determine the time course of dd-cfDNA expression during the first year after lung transplantation. 2. Validate the nCounter Gene Expression Assay platform and identify gene(s) associated with different types of acute rejection and/or infection.

Fertility Considerations and Lung Transplantation, a Scoping Review

<h3>Purpose</h3> Improved survival of transplant recipients has led to an increased focus on quality of life outcomes, including reproduction. Thirty two percent of lung transplants are performed on patients with childbearing potential. Compared to kidney and liver transplantation, lung transplantation has unique reproductive considerations including increased immunosuppression requirements, lifelong steroid use, and higher baseline risk for rejection. Lung transplant recipients may require or request assisted reproductive technology (ART) to conceive due to their underlying condition. Evidence-based decisions regarding reproduction are challenging for lung transplant recipients and their medical teams due to the lack of published literature on the subject in this specific population. We carried out a comprehensive scoping review of published research about reproductive considerations after lung transplantation. <h3>Methods</h3> An expert librarian performed a literature search on eight scholarly databases using controlled vocabulary and key words representing the concepts "lung transplantation" and "pregnancy" or "reproduction". Animal studies were excluded. No other limits were applied. Databases were searched from inception to March 8, 2021. Results (1474) were exported to a review management software, duplicates (488) were removed. Two independent reviewers screened 986 articles, 40 studies were included in data extraction. <h3>Results</h3> 40 articles met the inclusion criteria for full review, of these, 90% discussed pregnancy outcomes, 15% discussed fertility preservation, and 8% discussed pre-conception counselling, no articles discussed lactation. The majority of publications were case reports or case series describing at least 72 unique patients, and 86 unique pregnancies. Reporting was heterogeneous; the most frequently reported outcomes were maternal obstetric and transplant complications. <h3>Conclusion</h3> Successful pregnancy after lung transplantation is possible. Overall, little has been published regarding fertility considerations following lung transplantation. Further study is required to clarify natural and assisted reproductive outcomes. Interpretation of the existing data is challenging due to differences in outcome reporting, and publication bias. Standardized reporting is needed to facilitate understanding of this important aspect of post transplant care.

Low Levels of Hepatocyte-Specific Methylation in Cell-Free DNA Are a Strong Negative Predictor for Acute T Cell-Mediated Rejection Requiring Treatment Following Liver Transplantation.

Graft-derived cell-free DNA (gdcfDNA) quantification is a promising, minimally invasive tool for detecting acute T cell-mediated rejection (ATCMR) following liver transplantation (LT). We investigated the utility of measuring hepatocyte-specific methylation in cfDNA (HS-cfDNA) to quantify gdcfDNA, examining its accuracy in detecting ATCMR in a prospective, cross-sectional study. Blood was collected from LT recipients immediately prior to graft biopsy for suspected rejection. HS-cfDNA was quantified using droplet-digital polymerase chain reaction. Prebiopsy liver function tests (LFTs) and HS-cfDNA levels were correlated with biopsy results and the primary outcome of treated biopsy-proven acute rejection (tBPAR). A total of 51 patients were recruited; 37 had evidence of rejection on biopsy and 20 required treatment. As much as 11 patients needed inpatient treatment for rejection. HS-cfDNA significantly outperformed LFTs in identifying patients with tBPAR, particularly those needing inpatient treatment (area under the curve, 73.0%; 95% confidence interval, 55.4%-90.6%; P = 0.01). At a threshold of <33.5% of the total cfDNA fraction, HS-cfDNA had a specificity of 97%, correctly excluding tBPAR in 30/31 patients. Quantifying graft-specific methylation in cfDNA has a major advantage over previous gdcfDNA techniques: it does not require genotyping/sequencing, lending it greater feasibility for translation into transplantation care. Low levels of HS-cfDNA were a strong negative predictor for tBPAR (negative predictive value, 86%) and may have a future role in triaging patients prior to invasive graft biopsies.

Addressing the Ethical Challenges of Providing Kidney Failure Care for Children: A Global Stance.

Children with kidney failure require kidney replacement therapy (KRT), namely maintenance dialysis and kidney transplant. Adequate kidney failure care consists of KRT or conservative treatment with palliative care. In the context of kidney failure, children depend on parents who are their surrogate decision-makers, and the pediatric nephrology team for taking decisions about KRT or conservative care. In this paper, we discuss the ethical challenges that arise relating to such decision-making, from a global perspective, using the framework of pediatric bioethics. While many ethical dilemmas in the care of children with KRT are universal, the most significant ethical dilemma is the inequitable access to KRT in low & middle income countries (LMICs) where rates of morbidity and mortality depend on the family's ability to pay. Children with kidney failure in LMICs have inadequate access to maintenance dialysis, timely kidney transplant and palliative care compared to their counterparts in high income countries. Using case vignettes, we highlight how these disparities place severe burdens on caregivers, resulting in difficult decision-making, and lead to moral distress among pediatric nephrologists. We conclude with key action points to change this status-quo, the most important being advocacy by the global pediatric nephrology community for better access to affordable kidney failure care for children.

Relationship between donor fraction cell-free DNA and clinical rejection in heart transplantation.

Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell-free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest. Patients with heart transplantation were enrolled in two sequential, multi-center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA. A total of 835samples from 269subjects (57% pediatric) were included for this analysis, including 28samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p<.0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post-therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p<.0001). DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients.

Costs of Treatment of Acute Antibody-Mediated Rejection in Kidney Transplant Recipients

Antibody-mediated rejection (AMR) remains challenging in kidney transplant recipients. It may negatively impact the graft survival, and its treatment is associated to relatively high expenses. The aim of our study was to assess the costs of treatment of acute AMR in the Polish settings. A total of 11 kidney transplant recipients with acute AMR diagnosed between September 2016 and August 2019 and treated in our center were included. Direct costs of inpatient and outpatient care in the first year after AMR diagnosis from the perspective of a transplant center were retrospectively calculated. The costs of treatment of acute AMR were considerably high, with a mean 1-month cost of treatment 12,718 PLN (∼€2925; ∼3307 US dollars). That means that costs of management of kidney transplant recipients with acute AMR are almost 2-fold higher than hemodialysis. Intravenous immunoglobulin was responsible for the majority (55%) of costs. Treatment of acute AMR increases the costs of post-kidney transplant care in involved patients. Therefore, efforts should be made to minimize the risk for acute AMR. Despite its potential clinical benefits, management of acute AMR is even more expensive than dialysis. Therefore, further cost-effectiveness analyses are needed to justify the spending and to establish the best treatment regimens.