Successful Organ Transplantation Research Articles

Organ trafficking and the legal framework in India: a critical analysis of the transplantation of human organs and tissues act, 1994

Organ trafficking, due to its subtle nature, is a less-addressed form of trafficking, among others. It has been decades that the first-ever successful organ transplantation took place. Since then, medical science has advanced in leaps and bounds to gift us another chance of life, even in cases of acute organ failures. However, this has created a huge demand for transplantable organs building an unbridgeable gap between its demand and supply, which on the other hand, has generated booming markets for the illegal sale of organs leading to organized crime of organ trafficking, especially in the developing nations. The Transplantation of Human Organs Act (THOA), 1994, was enacted to provide regulatory frameworks and prevent the commercialization of human organs in India. Although THOA, with its latest amendments and rules, is somewhat successful in curbing the menace, recent studies show that it has failed to achieve its goals largely. The authors in this paper argue that the existing laws in India dealing with organ trades and trafficking are inadequate, in comprehensive, and lags far behind compared to the advancements in medical technologies and report the findings of a systematic analysis of THOA, highlight inadequacies, and recommends relevant reforms.

Anti-HLA antibodies in recipients of CD19 versus BCMA-targeted CAR T-cell therapy

Antibodies against foreign human leukocyte antigen (HLA) molecules are barriers to successful organ transplantation. B cell–depleting treatments are used to reduce anti-HLA antibodies but have limited efficacy. We hypothesized that the primary source for anti-HLA antibodies is long-lived plasma cells, which are ineffectively targeted by B cell depletion. To study this, we screened for anti-HLA antibodies in a prospectively enrolled cohort of 49 patients who received chimeric antigen receptor T-cell therapy (CARTx), targeting naïve and memory B cells (CD19-targeted, n = 21) or plasma cells (BCMA-targeted, n = 28) for hematologic malignancies. Longitudinal samples were collected before and up to 1 year after CARTx. All individuals were in sustained remission. We identified 4 participants with anti-HLA antibodies before CD19-CARTx. Despite B cell depletion, anti-HLA antibodies and calculated panel reactive antibody scores were stable for 1 year after CD19-CARTx. Only 1 BCMA-CARTx recipient had pre-CARTx low-level anti-HLA antibodies, with no follow-up samples available. These data implicate CD19neg long-lived plasma cells as an important source for anti-HLA antibodies, a model supported by infrequent HLA sensitization in BCMA-CARTx subjects receiving previous plasma cell–targeted therapies. Thus, plasma cell–targeted therapies may be more effective against HLA antibodies, thereby enabling improved access to organ transplantation and rejection management.

An Efficient Allocation for Lung Transplantation Using Ant Colony Optimization

A relationship between lung transplant success and many features of recipients’/donors has long been studied. However, modeling a robust model of a potential impact on organ transplant success has proved challenging. In this study, a hybrid feature selection model was developed based on ant colony optimization (ACO) and k-nearest neighbor (kNN) classifier to investigate the relationship between the most defining features of recipients/donors and lung transplant success using data from the United Network of Organ Sharing (UNOS). The proposed ACO-kNN approach explores the features space to identify the representative attributes and classify patients’ functional status (i.e., quality of life) after lung transplantation. The efficacy of the proposed model was verified using 3,684 records and 118 input features from the UNOS. The developed approach examined the reliability and validity of the lung allocation process. The results are promising regarding accuracy prediction to be 91.3% and low computational time, along with better decision capabilities, emphasizing the potential for automatic classification of the lung and other organs allocation processes. In addition, the proposed model recommends a new perspective on how medical experts and clinicians respond to uncertain and challenging lung allocation strategies. Having such ACO-kNN model, a medical professional can summarize information through the proposed method and make decisions for the upcoming transplants to allocate the donor organ.

From the Wright Brothers to the A380: Developing Transplantation Takes Teams of Teams.

From the Wright Brothers to the A380: Developing Transplantation Takes Teams of Teams.

Contemporary considerations in solid organ transplantation utilizing DCD donors

IntroductionDonation after cardiac death (DCD) has been leading the way to help bridge the growing gap between availability of donors and recipients on waitlist. With advances in technology and our understanding of DCD donation the safety profile is growing. It is becoming an increasing viable option even in marginal settings. DiscussionThe ethos surroundings DCD is still a matter of contention but there is support and collaboration from larger societies and establishments with development of standardizing protocols. Preparation is key. Experience of the procurement and transplanting surgeons are pivotal. There are multiple moving parts and for the success of a DCD program, dedication is needed from the donor hospitals, organ procurement organizations and the transplant centers. Previous practices based on anecdotal experiences are now either supported by or refuted by increasing evidence and data, based on the development of consensus-based guidelines with the end goal of having uniform outcomes. Normothermic regional and machine perfusion have expanded options in the DCD world, challenging the limits and expanding our paradigm. Recognition of the weaknesses and organ specific complications allow the clinician to make choices for optimal outcomes. These advancements have allowed outcomes to be optimized. ConclusionsExpanding the organ donor pool is one solution to increase the availability of organs for transplantation. Increasing the attention to and the use of DCD organs combined with machine and normothermic perfusion is a future strategy to obtain ongoing clinical success in organ transplantation and lower the waiting list mortality.

210.6: COVID-19 Positive Donor Organs in Transplantation

Introduction: Due to unknown transmission risks, donors with acute COVID-19 infection manifested by positive PCR test were ineligible for organ donation in the past. We report our experience with 6 donors with acute COVID-19 infection whose organs were used for transplantation. Methods: Retrospective review of outcomes of transplantation from COVID-19 positive donors. Results: Organs from six brain dead donors were utilized for transplantation. Donors were tested with COVID-19 PCR either on nasopharyngeal swabs or Brochoalveolar lavage specimens or both. Heart, liver and kidney were used for transplant from 1 donor, heart was utilized from 2 and liver from 3 of the donors. Three donors had discrepancy in results with a negative nasopharyngeal PCR, but positive BAL specimen. One donor had symptomatic COVID-19 infection (pneumonia) and all others were asymptomatic. Cycle threshold was >25. Recipients included 3 heart transplant, 3 liver transplant and 1 combined liver-kidney transplant. All recipients had completed full vaccination series, and three received additional post transplant pre-exposure prophylaxis with Tixagevimab/Cligavimab. Standard post transplant immunosuppression with steroids, CNI and antimetabolite was used. Two heart transplant recipients underwent post transplant treatment for AMR. There were no post transplant COVID infections with of median follow up of 40 days. All patients and grafts are doing well. Conclusion: Successful transplantation of organs from donors with COVID-19 infection is feasible. Appropriate donor and recipient selection and risk assessment is essential and long term follow up to rule out any transmittable risks of donor derived infection.

Comparison of Personality and Psychological Characteristics in Successful and Unsuccessful Organ Transplant Patients

Comparison of Personality and Psychological Characteristics in Successful and Unsuccessful Organ Transplant Patients

210.8: Timely Lower Respiratory SARS-CoV-2 Testing of All Potential Organ Donors Leads to Successful Transplantation of Organs From SARS-CoV-2+ Donors

210.8: Timely Lower Respiratory SARS-CoV-2 Testing of All Potential Organ Donors Leads to Successful Transplantation of Organs From SARS-CoV-2+ Donors

Organ Transplant From SARS-CoV-2–Positive Donors: A Brazilian Experience

Since March 2022, donors with detectable SARS-CoV-2 RNA have been accepted for extrapulmonary organ transplants in Brazil. In this report, we described 11 successful organ transplants (6 kidney, 5 liver) from 5 asymptomatic infected donors.

Mitochondria and ischemia reperfusion injury.

This review describes the role of mitochondria in ischemia-reperfusion-injury (IRI). Mitochondria are the power-house of our cells and play a key role for the success of organ transplantation. With their respiratory chain, mitochondria are the main energy producers, to fuel metabolic processes, control cellular signalling and provide electrochemical integrity. The mitochondrial metabolism is however severely disturbed when ischemia occurs. Cellular energy depletes rapidly and various metabolites, including Succinate accumulate. At reperfusion, reactive oxygen species are immediately released from complex-I and initiate the IRI-cascade of inflammation. Prior to the development of novel therapies, the underlying mechanisms should be explored to target the best possible mitochondrial compound. A clinically relevant treatment should recharge energy and reduce Succinate accumulation before organ implantation. While many interventions focus instead on a specific molecule, which may inhibit downstream IRI-inflammation, mitochondrial protection can be directly achieved through hypothermic oxygenated perfusion (HOPE) before transplantation. Mitochondria are attractive targets for novel molecules to limit IRI-associated inflammation. Although dynamic preservation techniques could serve as delivery tool for new therapeutic interventions, their own inherent mechanism should not only be studied, but considered as key treatment to reduce mitochondrial injury, as seen with the HOPE-approach.

Multidrug-Resistant and Extended-Spectrum β-Lactamase Gram-Negative Bacteria in Bilateral Lung Transplant Recipients: Incidence, Risk Factors, and In-Hospital Mortality

In recent decades, the incidence of multidrug-resistant (MDR) and extended-spectrum β-lactamase (ESBL) gram-negative (GN) bacteria has increased progressively among lung transplantation (LT) recipients. A prompt diagnosis, prevention, and management of these pathogens remain the cornerstone for successful organ transplantation. What are the incidence of MDR and ESBL GN bacteria within the first 30days after LT and related risk of in-hospital mortality? What are the potential clinical predictors of isolation of MDR and ESBL GN bacteria? All consecutive LT recipients admitted to the ICU of the University Hospital of Padua (February 2016-December 2021) were screened retrospectively. Only adult patients undergoing the first bilateral LT and not requiring invasive mechanical ventilation, extracorporeal membrane oxygenation, or both before surgery were included. MDR and ESBL GN bacteria were identified using invitro susceptibility tests and were isolated from the respiratory tract, blood, urine, rectal swab, or surgical wound or drainage according to a routine protocol. One hundred fifty-three LT recipients were screened, and 132 were considered for analysis. Median age was 52 years (interquartile range, 41-60 years) and 46 patients (35%) were women. MDR and ESBL GN bacteria were identified in 45 patients (34%), and 60%of patients demonstrated clinically relevant infection. Pseudomonas aeruginosa (n= 22 [49%]) and Klebsiella pneumoniae (n= 17 [38%]) were frequently isolated after LT from the respiratory tract (n= 21 [47%]) and multiple sites (n= 18 [40%]). Previous recipient-related colonization (hazard ratio [HR], 2.48 [95%CI, 1.04-5.90]; P= .04) and empirical exposure to broad-spectrum antibiotics (HR, 6.94 [95%CI, 2.93-16.46]; P< .01) were independent predictors of isolation of MDR and ESBL GN bacteria. In-hospital mortality of the MDR and ESBL group was 27%(HR, 6.38 [95%CI, 1.98-20.63]; P< .01). The incidence of MDR and ESBL GN bacteria after LT was 34%, and in-hospital mortality was six times greater. Previous recipient-related colonization and empirical exposure to broad-spectrum antibiotics were clinical predictors of isolation of MDR and ESBL GN bacteria.

Post-transplant Diabetes Mellitus: What Physicians Need to Know.

Post-transplant diabetes mellitus (PTDM) is a common problem among solid organ transplant recipients contributing to morbidity and affecting patient as well as graft survival adversely. It can occur at any period following transplantation, but maximum incidence is observed in the first few months, with a second peak after a few years after transplantation. The pathogenesis is complex and poorly understood, however, it is associated with both dysfunctional beta-cells and insulin resistance. Both nonpharmacologic and antidiabetic therapies are important for adequate glycemic control. This point of view article provides a short review on PTDM in solid organ transplantation (SOT) recipients from a general physician's perspective.

Israeli Medical Experts’ Knowledge, Attitudes, and Preferences in Allocating Donor Organs for Transplantation

Medical advancement has increased the confidence in successful organ transplants in end-stage patients. As the waitlist of organ demand is multiplying, the organ allocation process is becoming more crucial. In this situation, a transparent and efficient organ allocation policy is required. This study evaluates the preferences of medical experts to substantial factors for allocating organs in different hypothetical scenarios. Twenty-five medical professionals with a significant role in organ allocation were interviewed individually. The interview questionnaire comprised demographic information, organ donation status, important organ allocation factors, public preference knowledge, and experts’ preferences in different hypothetical scenarios. Most medical experts rated the waiting time and prognosis as the most important, while the next of kin donor status and care and contribution to the well-being of others were the least important factors for organ allocation. In expert opinion, medical experts significantly considered public preferences for organ allocation in making their decisions. Altogether, experts prioritized waiting time over successful transplant, age, and donor status in the hypothetical scenarios. In parallel, less chance of finding another organ, donor status, and successful transplant were prioritized over age. Medical experts are the key stakeholders; therefore, their opinions are substantial in formulating an organ allocation policy.

Laboratory support of ABO antibody monitoring for ABO-incompatible solid organ transplantation.

The accurate measurement of ABO antibodies is essential for successful ABO-incompatible solid organ transplantation. Titration using two-fold dilution is considered a standard method and is applied in most laboratories. However, this titration method has inherent limitations, including differences in methods between laboratories, a lack of standardization, its semiquantitative nature, and the difficulty of considering the results to be representative of the in vivo activity of ABO antibodies. Various measurement methods other than titration have been developed, and new methods continue to be introduced. Physicians and laboratory specialists who are involved in ABO-incompatible solid organ transplantation need to fully understand these methods for optimal patient management.

Misidentification of preformed anti-HLA-DP antibodies leads to antibody-mediated kidney transplant rejection: a case report

BackgroundPatients who are HLA-sensitized are at high risk for early antibody-mediated rejection (AMR) and worse outcomes. Therefore, it is crucial to detect the presence of donor-specific antibodies (DSAs) using pretransplant antibody identification and crossmatch assays. An error in antibody identification can lead to disastrous clinical outcomes. We present a case of acute AMR associated with preformed HLA-DPα and HLA-DPβ DSAs that were not identified before transplantation.Case presentationA 27-year-old woman received a second kidney transplant from a deceased donor. Her pretransplant panel-reactive antibody level was 94%. The complement-dependent cytotoxicity crossmatch was negative for T and B cells at the time of transplantation. She experienced early acute AMR proven by a kidney biopsy. Single antigen bead testing of the patient’s serum at the time of rejection as well as the pre-second transplant serum revealed strong antibodies against the DPA1*01:03 and DPB1*02:01 alleles in the second donor. These antibodies were not identified by phenotypic bead assay during the patient’s time on the waiting list. The patient was treated with plasmapheresis and anti-thymocyte globulin. However, she experienced abdominal pain on day 37 post-transplantation. Surgical exploration revealed a laceration on the transplanted kidney, which was then repaired. Subsequently, infected hematoma was suspected and the transplanted kidney was removed.ConclusionThe present case highlights the clinical significance of preformed HLA-DPα and HLA-DPβ DSAs. Accuracy in determination of HLA antibodies before transplantattion is critical for transplant outcome. HLA-DP typing and single antigen bead testing are recommended for a precise antibody interpretation, especially in highly sensitized patients. Careful interpretation of antibody testing results is essential for the success of organ transplantation.

Ethical Analysis of Appropriate Incentive Measures Promoting Organ Donation in Bangladesh.

Bangladesh, a Muslim-majority country, has a national organ donation law that was passed in 1999 and revised in 2018. The law allows living-related and brain-dead donor organ transplantation. There are no legal barriers to these two types of organ donations, but there is no legislation providing necessary costs and incentive measures associated with successful organ transplants. However, many governments across the globe provide different types of incentives for motivating living donors and families of deceased donors. This study assesses the merits and demerits of incentive measures already in use around the world and proposes ethical measures that can promote organ donation in Bangladesh. The primary focus of this paper is to present an ethical analysis of the comparison of incentive measures on organ donation between Bangladesh and the Islamic Republic of Iran as two Muslim countries that operate organ donation for transplantation practices according to Islamic principles. In this paper, I mainly argue that providing a fixed bare minimum financial incentive measure to distantly related living donors and families of deceased donors will encourage Bangladeshis to donate organs in a manner that is ethically justifiable, morally permissible, and socio-economically appropriate. The government of Bangladesh should revise the existing biomedical law to include a provision related to incentive measures and set a strict policy to properly regulate these measures as key stewardship that can ethically promote organ donation for transplantation.

Approaches to isolating and purifying nucleic acids from blood for genotyping human leukocytic antigen

Donorrecipient histocompatibility results from the presence on cell membranes of the main protein complex of histocompatibility and is a key condition for successful transplantation of cells, tissues, and organs. To determine histocompatibility, human leukocyte antigen is genotyped, and its accuracy relied significantly on the quality and quantity of nucleic acids obtained from the biomaterial. In laboratory practice, the most pure and intact deoxyribonucleic and ribonucleic acids are extracted from the blood; however, the choice of an accessible, effective, time-efficient, and viable method for their production remains challenging. The methods of isolation and purification of nucleic acids from the blood include organic extraction, salting out, and use of spin columns and magnetic particles (bidids), and their advantages and disadvantages, efficiency indicators, practicality, and cost were compared. The selection of the peripheral blood as a source of genetic material for genotyping human leukocyte antigen is justified. Experimental data comparing the pricequality ratio of commercial protocols for the extraction of deoxyribonucleic and ribonucleic acids from blood were analyzed. Prospects of modification of procedures for isolation and purification of nucleic acids from biomaterial for sequencing of genes of human leukocyte antigen classes I and II to increase efficiency of high-tech care are evaluated. Generally, the need for affordable and effective protocols for the extraction of deoxyribonucleic and ribonucleic acids from minimal biomaterial volumes stimulates the optimization and modification of existing protocols and the creation of new methods on new physicochemical principles.

Physiological aspects of pig kidney xenotransplantation and implications for management following transplant.

Successful organ transplantation between species is now possible, using genetic modifications. This article aims to provide a comprehensive overview of the differences and similarities in kidney function between humans, primates, and pigs, in preparation for pig-allograft to human xenotransplantation. The kidney, as the principal defender of body homeostasis, acts as a sensor, effector, and regulator of physiologic feedback systems. Considerations are made for anticipated effects on each system when a pig kidney is placed into a human recipient. Discussion topics include anatomy, global kidney function, sodium and water handling, kidney hormone production and response to circulating hormones, acid-base balance, and calcium and phosphorus handling. Based on available data, pig kidneys are anticipated to be compatible with human physiology, despite a few barriers.

OPTN/SRTR 2020 Annual Data Report: Living Donor Collective

The first successful solid organ transplant was a living donor kidney transplant in 1954. Since then, living donation has been an important source of organs for kidney and liver transplants in the United States. Unfortunately, the demand for organs has not kept pace with the supply, and unlike deceased donor transplant, there has been little growth in the number of living donor transplants over the past decade. To better understand possible barriers to living donation and long-term risks attributable to donation, the Health Resources and Services Administration (HRSA) directed the Scientific Registry of Transplant Recipients (SRTR) to establish a national registry of all living donor candidates and donors evaluated at US transplant programs to acquire lifetime follow-up information. Other goals include understanding the factors associated with candidate approval and variation in approval practices across centers. A pilot program was conducted from June 2018 through September 2020 to inform baseline data collection and registration processes. In September 2020, the registry began recruiting additional sites evaluating candidates for living donation. Here, we describe candidates registered at participating living donor kidney and liver programs, from June 2018 through the end of 2020. Not all programs submitted data throughout the whole period. Data for kidney and liver living donor candidates are presented separately.

POS-762 UNUSUAL PRESENTATION OF TACROLIMUS TOXICITY – CHOLESTATIC SYNDROME IN RENAL ALLOGRAFT RECIPIENT

Tacrolimus (TAC) holds a key role to a successful organ transplantation and allograft survival in today’s world, but has a narrow therapeutic window, necessitating therapeutic drug monitoring to maintain efficacy and minimize toxicity. Except transaminitis, hepatotoxicity due to TAC, has rarely been reported in a renal allograft recipient. We report here an unusual presentation of TAC toxicity in in a live donor renal allograft recipient 5 years (yr) post successful engraftment presented as cholestatic hepatitis without transaminitis. 32 year male, sister to brother compatible (O Positive), 3/6 HLA mismatch, crossmatch negative by CDC and flow cytometry, 5 years post renal allograft recipient hospitalized with deep jaundice and unremarkable systemic examination. Pre transplant and recent evaluation was inconclusive for acute/chronic infection/inflammation or acute hematological etiology for cholestasis. Compliance with daily therapeutic dose of maintenance immunosuppression was noted. TAC trough levels was 4.7. In a week long management, treatment included modified immunosuppression - Mycophenolate (MMF) stopped, Intravenous steroids, TAC (3mg/day), antibiotics and ursodeoxycholic acid to relieve cholestasis. Thoroughly evaluated, ultrasound abdomen, graft kidney and doppler of spleno-portal axes was also unremarkable, we planned for MRCP and liver biopsy, but his hyperbilirubinemia improved spontaneously and persistently following decrease in TAC dose (1mg/day) on 4th day of hospitalization and subsequently withdrawal and switching to everolimus. To the best of our knowledge Yadav et al. and Mesar et al. have reported isolated cases of cholestatic syndrome with transaminitis in immediate post-renal transplant period respectively attributed to TAC. Our patient presented with direct hyperbilirubinemia 5yr post-transplant without transaminitis, maintained on therapeutic dose and trough levels of TAC. Evaluated thoroughly for cholestasis, clinical, biochemical improvement occurred immediately following tapering and subsequently stopping TAC. Trend of Bilirubin, Liver enzymes, TAC dose and Creatinine levels Cholestatic syndrome in renal allograft recipients due to TAC has rarely been reported. We thus conclude that cholestatic jaundice in our patient was attributed to therapeutic dose of TAC, having excluded other possible causes. The event can thus occur with therapeutic dose or trough levels of TAC and anytime in the post-transplant course. Thus we propose that transplant Physicians should be vigilant in following up their allograft recipients and further insight on the pharmacokinetic and pharmacodynamic profile of TAC should be thought about.