Organ Procurement Transplant Research Articles

Depletion of CD4 and CD8 Positive T Cells Impairs Venous Thrombus Resolution in Mice.

Resolution of deep venous thrombosis involves coordinated inflammatory processes. T cells regulate inflammation in vivo and modulate vascular remodeling in other settings, but their role in venous thrombus resolution remains undefined. To determine the role of T cells in venous thrombus resolution in vivo, stasis induced thrombi were created by vena cava ligation in outbred CD-1 mice. CD4 and CD8 positive T cells, as determined by flow cytometry, were present in thrombi both during thrombus formation and resolution. Depletion of the CD4 and CD8 positive T cells by antibody treatment selectively impaired thrombus resolution compared to animals treated with isotype control antibodies, without an effect on venous thrombus formation. Quantitation of intra-thrombus macrophage numbers, fibrinolytic marker expression, and gelatinolytic activity by zymography revealed that T cell depletion decreased the number of macrophages, reduced the expression of fibrinolytic marker urokinase plasminogen activator (uPA), and decreased the activity of matrix metalloprotinease-9 (MMP-9). These data implicate CD4 and CD8 positive T cells in functionally contributing to venous thrombus resolution, thus representing a potential therapeutic target, but also underscoring potential risks involved in T cell depletion used clinically for solid organ and hematopoietic transplantation procedures.

Legal issues of death donorship in Ukraine

The purpose of the paper is to investigate the topic of posthumous donation and to consider the legal models for the legal regulation of the removal of organs from deceased persons - the "presumption of consent" and the "presumption of disagreement" that have developed in the world community. Research methods: documentary analysis and synthesis, comparative analysis, objective truth, cognitive-analytical, etc. Results: the practice of applying each of the legal models of organ transplantation from a deceased donor has been clarified. Discussion: current state of national legal regulation of organ transplantation from a deceased donor. The issue of transplantation has long required the development of a current legal framework in Ukraine that meets European standards, in particular. At the moment, the adoption of "On the Use of Transplantation of Anatomical Materials to Man" dated 17.05.2018 indicates the stabilization of state policy in this field, however, some aspects of the implementation of the law necessitate additional interpretation or adoption of normative legal acts. In Europe, the legal basis for the development of such a phenomenon as donation is much better developed than in our country, which is more positively reflected in the living and health standards of these countries. However, the organ transplant procedure in Ukraine is on the way to its widespread practical application. The following major problems of posthumous donation in Ukraine can be distinguished as: insufficiently clear legal definition of the conceptual categorical apparatus and the mechanism of applying the presumption of consent and disagreement; the absence, and therefore the need, of establishing a register of recipients; critical level of public funding for this field of medicine; insufficient coverage of the topic by the state and, as a consequence, the need for society in the field of organ donation. The above list of issues is not exhaustive and therefore requires a comprehensive legislative, scientific and medical approach.

Calcium Score of Iliac Vessels and Relative Sparing of the External Iliac Artery Could Recommend Surgical Arterial Graft Selection

Background: Calcified plaque build-up can increase the risk of subsequent vascular complications in pelvic solid organ transplantation and vascular bypass procedures. Objectives: To assess the atherosclerotic calcification of pelvic vessels by measuring Agatston score and comparing it among abdominal aorta, common iliac artery (CIA), external iliac artery (EIA), and common femoral artery (CFA). Patients and Methods: We retrospectively reviewed the unenhanced computed tomography scans of 197 patients from August 2016 to March 2018. Using calcium-scoring software, we examined the distribution map of calcified plaques, focusing on four different arterial segments -the abdominal aorta, the common iliac artery (CIA), the external iliac artery (EIA), and the common femoral artery (CFA)- to determine which one showed the least mural calcification. Results: A total of 197 patients (118 men, 79 women) with a mean age of 61.19 ± 10.8 years were included in this study. The right EIA segment had the lowest average calcification score (92.1 ± 18.2), including 180 cases (91.4%) of zero calcification, followed by 178 cases (90.4%) of zero calcification in the left EIA. When adjustments were made for age, gender, smoking status, diabetes, hypertension and hyperlipidemia, the odds ratio (OR) of the left EIA for reaching a higher calcium score level was 1.19 (P = 0.44) times greater than the reference group (right EIA). The ratio was markedly higher in the abdominal aorta segment (OR = 146.7.4, P < 0.001), followed by the right CIA (OR = 42.5, P < 0.001), the left CIA (OR = 27.3, P < 0.001), the right CFA (OR = 3.96, P < 0.001), and the left CFA (OR = 3.51, P < 0.001). Conclusion: The study demonstrates a significantly less calcific plaque burden in EIA compared to the adjacent arterial bed.

An optimization framework to determine an optimal local sharing variance for organ allocation

One of the main elements affecting the performance of the organ transplantation system is the set of organ allocation boundaries that limits the number of organs shared among regions. To overcome these boundary limits, members of the Organ Procurement Transplant Network - OPTN - (including, transplant hospitals, Organ Procurement Organizations (OPO), medical/scientific members, among others) can propose a variance to the current allocation system to allocate organs differently than the OPTN policies. Over the years, several variances have been enacted by different members for various organs. In this study, we focus on the analysis of sharing variances which allow allocating organs within participating members before offering them at other levels. This type of variance has been successfully implemented in the past. For example, Florida and Tennessee created the Statewide Sharing program whereby kidneys are made available within-state donor service areas before they are made available for regional or national allocation. This program removed geographic disparities within those two states and resulted in better performance of the system in the states. Given these success stories, we propose a multi-period optimization model that can be used to determine the best policy for a local sharing program for any given OPO. We use liver allocation for the GALL OPO (i.e., LifeLink of Georgia) in the state of Georgia (USA) as a test case; however, our approach could be used for a variety of organs in any OPO.

Valve Replacement in Children with Single Ventricle Physiology.

Severe atrioventricular valve (AVV) or semilunar valve (SLV) regurgitation in the setting of a single ventricle physiology may proceed to valve replacement if repair strategies fail. Outcome data for these children are limited. We present transplant-free survival of a case series of children with single ventricle physiology undergoing either atrioventricular replacement (AVVR) or semilunar valve replacement (SLVR) from a multi-institutional, US-based registry (Pediatric Cardiac Care Consortium-PCCC). Outcomes were derived from PCCC and by linkage with the National Death Index (NDI) and Organ Procurement Transplant Network (OPTN). Fifty children with single ventricle physiology were identified to have received either AVVR (n = 38) or SLVR (n = 12). There were 17 in-hospital deaths including 8 intraoperative deaths (all intraoperative deaths were among children requiring AVVR). The in-hospital mortality was 42% and 8% for AVVR and SLVR, respectively. Among the 33 children surviving to hospital discharge, follow-up was available in 15 (46%). Death or cardiac transplant after hospital discharge occurred in 10-death in 4 (all among those requiring AVVR), cardiac transplant in 6 (2 following AVVR, 4 following SLVR). Valve replacement in children with single ventricle physiology, especially AVVR, is associated with poor outcomes. Alternative palliation strategies should be considered in children with single ventricle physiology with significant AVV or SLV regurgitations.

Advancing American Kidney Health: Perspective from DaVita, Inc.

Advancing American Kidney Health (AAKH) ([1][1]) has the potential to transform kidney care in America and outlines what the kidney care community has been striving to achieve for decades, as described in the recently released Kidney Care Partners Kidney Care First initiative ([2][2]). This includes

No Time to Wait: Optimizing Use of Deceased Donor Kidneys.

The critical shortage of organs available for transplantation is now well recognized, with individual transplant centers responsible for managing ever-growing lists of patients awaiting an offer for a kidney that will improve their quality of life and survival. What is less known, particularly to

Late-Onset Central Nervous System Posttransplant Lymphoproliferative Disorder After Lung Transplantation:A Case Report

Posttransplant lymphoproliferative disorder (PTLD) is caused by uncontrolled proliferation of lymphoid cells after a hematopoietic stem cell or solid organ transplant procedure related to the Epstein-Barr virus (EBV) infection. A primary central nervous system (CNS) PTLD (CNS-PTLD) is rare and important to distinguish from an intracranial lesion after transplantation.A 66-year-old man with pulmonary arterial hypertension who underwent living-donor lung transplantation 9 years prior noticed disorientation regarding route and dates. Brain magnetic resonance imaging revealed multiple white matter lesions and fluorodeoxyglucose (FDG) positron emission tomography showed FDG uptake in the brain and skin. CNS-PTLD was diagnosed by craniotomy biopsy and EBV-encoded RNA was positive in in situ hybridization findings and elevated in brain tissue. The treatment was started with immunosuppressant reduction and whole brain radiotherapy. But the condition progressed rapidly over 2 months after the first symptom and the patient was passed away 25 days after hospitalization.CNS-PTLD can occur several years after transplantation and it is necessary to keep in mind to distinguish brain disease because early diagnosis and treatment are important.

Use of rapid Model for End-Stage Liver Disease (MELD) increases for liver transplant registrant prioritization after MELD-Na and Share 35, an evaluation using data from the United Network for Organ Sharing.

The Model for End-Stage Liver Disease (MELD) score has been successfully used to prioritize patients on the United States liver transplant waiting list since its adoption in 2002. The United Network for Organ Sharing (UNOS)/Organ Procurement Transplantation Network (OPTN) allocation policy has evolved over the years, and notable recent changes include Share 35, inclusion of serum sodium in the MELD score, and a ‘delay and cap’ policy for hepatocellular carcinoma (HCC) patients. We explored the potential of a registrant’s change in 30-day MELD scores (ΔMELD30) to improve allocation both before and after these policy changes. Current MELD and ΔMELD30 were evaluated using cause-specific hazards models for waitlist dropout based on US liver transplant registrants added to the waitlist between 06/30/2003 and 6/30/2013. Two composite scores were constructed and then evaluated on UNOS data spanning the current policy era (01/02/2016 to 09/07/2018). Predictive accuracy was evaluated using the C-index for model discrimination and by comparing observed and predicted waitlist dropout probabilities for model calibration. After the change to MELD-Na, increased dropout associated with ΔMELD30 jumps is no longer evident at MELD scores below 30. However, the adoption of Share 35 has potentially resulted in discrepancies in waitlist dropout for patients with sharp MELD increases at higher MELD scores. Use of the ΔMELD30 to add additional points or serve as a potential tiebreaker for patients with rapid deterioration may extend the benefit of Share 35 to better include those in most critical need.

Estimated Association Between Organ Availability and Presumed Consent in Solid Organ Transplant

Presumed consent, or an opt-out organ transplant policy, has been adopted by many countries worldwide to increase organ donation. The implication of such a policy for transplants in the United States is uncertain, however. To simulate the potential implications of a presumed consent policy in the United States. In a decision analytical model, a simulation model was developed using cohort data from January 1, 2004, to December 31, 2014, in the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research files. All US patients (n = 524 359) who were on the waiting list for at least 1 solid organ and all deceased organ donors during the study period were included in the analyses. All data and statistical analyses were performed from January 30, 2019, to July 31, 2019. Increase in the organs available for donation and life-years gained associated with a 5%, 15%, or 25% increase in deceased donors, based on the published changes from a presumed consent policy. This study considered 524 359 unique candidates (aged ≥18 years; 320 908 [61.2%] male) for a solid organ transplant from January 1, 2004, to December 31, 2014. With a base case scenario of a 5% presumed consent-associated increase in donors, the removals (owing to death or illness) from the waiting list for all organs would have an associated 3.2% to 10.4% mean reduction, depending on the random or ideal allocation of new organs to patients on the waiting list. Sensitivity analyses showed that waiting list removals could be decreased up to 52%; however, this reduction was not enough to completely eliminate waiting list removals during the study period. The biggest estimated increases in annual life-years gained associated with a presumed consent policy were in kidney transplant candidates (95% CIs by deceased donor increase: 5% increase, 3440-3466 years; 15% increase, 10 321-10 399 years; 25% increase, 17 201-17 332 years) and liver transplant candidates (95% CIs by deceased donor increase: 5% increase, 898-905 years; 15% increase, 2693-2714 years; 25% increase, 4448-4523 years). Adoption of a presumed consent policy could result in a 4295-year (95% CI, 4277-4313 years) to 11 387-year (95% CI, 11 339-11 435 years) increase in life-years, accounting for the survival advantages associated with a transplant. In this study, presumed consent was estimated to be associated with modest but important improvement in the number of organ transplants and increases in life-years gained for patients awaiting an organ transplant. Further consideration and even debate about the ethical and public policy implications of a presumed consent policy are warranted.

Beyond Survival in Solid Organ Transplantation: A Summary of Expert Presentations from the Sandoz 6th Standalone Transplantation Meeting, 2018.

Beyond Survival in Solid Organ Transplantation: A Summary of Expert Presentations from the Sandoz 6th Standalone Transplantation Meeting, 2018.

Role of Preimplantation Biopsies in Kidney Donors With Acute Kidney Injury

Role of Preimplantation Biopsies in Kidney Donors With Acute Kidney Injury

Impact of induction immunosuppression on patient survival in heart transplant recipients treated with tacrolimus and mycophenolic acid in the current allocation era.

The practice of induction therapy with either rabbit anti-thymocyte globulin (r-ATG) or interleukin-2 receptor antagonists (IL-2RA) is common among heart transplant recipients. However, its benefits in the setting of contemporary maintenance immunosuppression with tacrolimus/mycophenolic acid (TAC/MPA) are unknown. We compared post-transplant mortality among three induction therapy strategies (r-ATG vs IL2-RA vs no induction) in a retrospective cohort analysis of heart transplant recipients maintained on TAC/MPA in the Organ Procurement Transplant Network (OPTN) database between the years 2006 and 2015. We used a multivariable model adjusting for clinically important co-morbidities, and a propensity score analysis using the inverse probability weighted (IPW) method in the final analysis. In multivariable IPW analysis, r-ATG (HR=1.23; 95% CI=1.05-1.46, P=0.01) remained significantly associated with a higher mortality. There was a trend toward having a higher mortality in the IL2-RA (HR=1.11; 95% CI=1.00-1.24, P=0.06) group. Subgroup analyses failed to show a patient survival benefit in using either r-ATG or IL2-RA among any of the subgroups analyzed. In this contemporary cohort of heart transplant recipients receiving TAC/MPA, neither r-ATG nor IL2-RA were associated with a survival benefit. On the contrary, adjusted analyses showed a significantly higher mortality in the r-ATG group and a trend toward higher mortality in the IL2-RA group. While caution is needed in interpreting treatment effects in an observational cohort, these data call into question the benefit of induction therapy as a common practice and highlight the need for more studies.

Organ donation after trauma: A 30-year review.

Over the past 30 years, the demographics, clinical characteristics, and management of trauma patients have changed dramatically. During this same period, the organ donor population has also changed. The interactions between these two demographic shifts have not been examined in a systematic way. We hypothesize that trauma victims continue to be an important source of organs. We set out to systematically examine traumatic donors in an attempt to identify opportunities to increase organ recovery and quality. In this retrospective analysis, we compared trauma donors (TDs) and non-TDs (NTDs) in the Scientific Registry of Transplant Recipients standard analysis files, a clinical data set collected by the Organ Procurement Transplant Network on all solid organ transplant candidates, donors, and recipients in the United States since 1987. Scientific Registry of Transplant Recipients contained data on 191,802 deceased donors. The percentage of TDs decreased from 55.3% in 1987 to 35.8% in 2016 (p < 0.001) primarily due to a steady increase in NTDs. Trauma donors are younger and have fewer comorbidities while the percentage of donors who were public health service high risk or who underwent donation after cardiac death were clinically similar. The TDs produce more organs/donor (3.5 vs. 2.4, p < 0.001), are more likely to yield an extrarenal organ, and exhibit lower (better) Kidney Donor Risk Index scores, a predictor of graft longevity. These better outcomes are maintained after stratifying by age. Over the past 30 years, the number of NTDs has increased much more than the number of TDs. However, TDs remain a critically important organ donor source, yielding more organs per donor, better quality kidneys, and a higher likelihood of extrarenal organs. Potential causes, such as improved resuscitation protocols, should be examined in the future. Retrospective review, level III.

Association of Racial Disparities With Access to Kidney Transplant After the Implementation of the New Kidney Allocation System

Inactive patients on the kidney transplant wait-list have a higher mortality. The implications of this status change on transplant outcomes between racial/ethnic groups are unknown. To determine if activity status changes differ among races/ethnicities and levels of sensitization, and if these differences are associated with transplant probability after implementation of the Kidney Allocation System. A multistate model was constructed from the Organ Procurement and Transplantation Network kidney transplant database (December 4, 2014, to September 8, 2016). The time interval followed Kidney Allocation System implementation and provided at least 1-year follow-up for all patients. The model calculated probabilities between active and inactive status and the following competing risk outcomes: living donor transplant, deceased donor transplant, and death/other. This retrospective cohort study included 42 558 patients on the Organ Procurement and Transplantation Network kidney transplant wait-list following Kidney Allocation System implementation. To rule out time-varying confounding from relisting, analysis was limited to first-time registrants. Owing to variations in listing practices, primary center listing data were used for dually listed patients. Individuals listed for another organ or pancreatic islets were excluded. Analysis began July 2017. Probabilities were determined for transitions between active and inactive status and the following outcome states: active to living donor transplant, active to deceased donor transplant, active to death/other, inactive to living donor transplant, inactive to deceased donor transplant, and inactive to death/other. The median (interquartile range) age at listing was 55.0 (18.0-89.0) years, and 26 535 of 42 558 (62.4%) were men. White individuals were 43.3% (n = 18 417) of wait-listed patients, while black and Hispanic individuals made up 27.8% (n = 11 837) and 19.5% (n = 8296), respectively. Patients in the calculated plasma reactive antibody categories of 0% or 1% to 79% showed no statistically significant difference in transplant probability among races/ethnicities. White individuals had an advantage in transplant probability over black individuals in calculated plasma reactive antibody categories of 80% to 89% (hazard ratio [HR], 1.8 [95% CI, 1.4-2.2]) and 90% or higher (HR, 2.4 [95% CI, 2.1-2.6]), while Hispanic individuals had an advantage over black individuals in the calculated plasma reactive antibody group of 90% or higher (HR, 2.5 [95% CI, 2.1-2.8]). Once on the inactive list, white individuals were more likely than Hispanic individuals (HR, 1.2 [95% CI, 1.17-1.3]) or black individuals (HR, 1.4 [95% CI, 1.3-1.4]) to resolve issues for inactivity resulting in activation. For patients who are highly sensitized, there continues to be less access to kidney transplant in the black population after the implementation of the Kidney Allocation System. Health disparities continue after listing where individuals from minority groups have greater difficulty in resolving issues of inactivity.

The innate immune response to allotransplants: mechanisms and therapeutic potentials.

Surgical trauma and ischemia reperfusion injury (IRI) are unavoidable aspects of any solid organ transplant procedure. They trigger a multifactorial antigen-independent inflammatory process that profoundly affects both the early and long-term outcomes of the transplanted organ. The injury associated with donor organ procurement, storage, and engraftment triggers innate immune activation that inevitably results in cell death, which may occur in many different forms. Dying cells in donor grafts release damage-associated molecular patterns (DAMPs), which alert recipient innate cells, including macrophages and dendritic cells (DCs), through the activation of the complement cascade and toll-like receptors (TLRs). The long-term effect of inflammation on innate immune cells is associated with changes in cellular metabolism that skew the cells towards aerobic glycolysis, resulting in innate immune cell activation and inflammatory cytokine production. The different roles of proinflammatory cytokines in innate immune activation have been described, and these cytokines also stimulate optimal T-cell expansion during allograft rejection. Therefore, early innate immune events after organ transplantation determine the fate of the adaptive immune response. In this review, we summarize the contributions of innate immunity to allograft rejection and discuss recent studies and emerging concepts in the targeted delivery of therapeutics to modulate the innate immune system to enhance allograft survival.

Simultaneous liver kidney transplantation.

Kidney injury is frequently seen in patients with end-stage liver disease from cirrhosis and liver failure. Among selected patients, simultaneous liver kidney (SLK) transplantation provides improved post-transplant graft and patient outcomes compared to liver transplantation (LT) alone. We conducted the review of the existing literature on SLK transplant criteria and outcomes. Since the introduction of the model for end-stage disease (MELD) score in 2002, there has been an increased use of SLK transplantation. The criteria for SLK allocation are relatively homogeneous among patients with end-stage renal disease with cirrhosis and among patients with cirrhosis and chronic kidney disease. However, these are quite heterogeneous among patients with cirrhosis and acute kidney injury (AKI), mainly because of inability to accurately differentiate cause of AKI, especially hepatorenal syndrome versus intrarenal aetiology. Clearly, there is an unmet need of urine biomarkers of tubular injury and/or clinical models to accurately stratify AKI aetiology and to predict renal recovery after LT as basis to best utilize the scarce donor kidney pool. In this regard, it remains to be seen whether recently implemented policies by the organ procurement transplant network can fulfil the goal of saving donor kidneys and optimal allocation of SLK.

The Collaborative Improvement and Innovation Network project to drive quality improvement.

The purpose is to describe an approach for improvement using an organized collaborative improvement framework where participants learn, apply, and share improvement ideas supported through a 3-year Organ Procurement Transplant Network (OPTN) project called Collaborative Improvement and Innovation Network (COIIN). The COIIN project, proposed as an alternative approach to monitoring transplant performance, supported collaboration, and improvement in 58 transplant hospitals and partner organ procurement organizations. The aim was to increase transplantation with a focus on increasing the utilization of moderate-to-high (50-100%) Kidney Donor Profile Index (KDPI) kidneys. Preliminary findings show increases in transplant rate and utilization of moderate-to-high KDPI kidneys was achieved in many participating organizations. Preliminary COIIN project results suggest that an improvement approach that supports collaborative improvement can be effective in driving improvement. The COIIN project involved the development of a change package of key interventions for three key areas: waitlist management, organ-offer acceptance, and care coordination. Additionally, a balanced scorecard approach using outcome, process, and relationship measures, was used and effective in driving improvement. The preliminary COIIN outcome and process results suggest that collaborative improvement does drive improvement and was well received in the transplant community. In the video, two of the authors describe the content of the review and present the main topics discussed in the article (http://links.lww.com/MOT/A22).

Living-Donor Organ Donation: Impact of Expansion of Genetic Relationship.

In Jordan, the history of organ transplantation started in 1972 with a kidney transplant from a deceased donor. At present, Jordan is in a good position with regard to organ transplantation among developing countries. It remains important to follow through with some decisions and enact laws that would increase the percentage of legal organ donations and transplant procedures. This has involved the expansion of relative degree donation. Until 2013, most relative degree donations involved 1st-degree and 2nd-degree relatives. The degree of genetical and legal relatives in living organ donation was then expanded to allow 4th- and 5th-degree relatives. This expansion to a 5th-degree relative came about when it was realized that the percentage of organ transplants in 2nd-degree relatives was high. Therefore, the idea of organ donation in these degrees may be beneficial, as it can lead to significantly higher numbers of organ donations.

Načela postupka presađivanja organa

The principles of human organ transplantation procedure must meet two requirements: the requirement of humanity, which all medical activities are based on, and the requirement for patients' protection and the preservation of human and personal rights of every human being, during one's lifetime and after death. In Serbian law, the following principles are established as fundamental ones: the protection of interests and dignity of the organ donor and the organ recipient; voluntarity; medical justification and safety; and equal availability of human organs. Every person having a medically established need and justification for human organ transplan-tation should be subject to equal conditions for receiving a human organ.