Organ Donation and Transplantation Registries Across the Globe: A Review of the Current State.

BACKGROUND: The current landscape of organ donation and transplantation (ODT) registries is not well established. This narrative review sought to identify and characterize the coverage, structure, and data capture of ODT registries globally. METHODS: We conducted a literature search using Ovid Medline and web searches to identify ODT registries from 2000 to 2023. A list of ODT registries was compiled based on publications of registry design, studies, and reports. Extracted data elements included operational features of registries and the types of donor and recipient data captured. RESULTS: We identified 129 registries encompassing patients from all continents except Antarctica. Most registries were active, received funding from government or professional societies, were national in scope, included both adult and pediatric patients, and reported patient-level data. Registries included kidney (n = 99), pancreas (n = 32), liver (n = 44), heart (n = 35), lung (n = 30), intestine (n = 15), and islet cell (n = 5) transplants. Most registries captured donor data (including living versus deceased) and recipient features (including demographics, cause of organ failure, and posttransplant outcomes) but there was underreporting of other domains (eg, donor comorbidities, deceased donor referral rates, waitlist statistics). CONCLUSIONS: This review highlights existing ODT registries globally and serves as a call for increased visibility and transparency in data management and reporting practices. We propose that standards for ODT registries, a common data model, and technical platforms for collaboration, will enable a high-functioning global ODT system responsive to the needs of transplant candidates, recipients, and donors.

Long-term Kidney Transplant Survival Across the Globe.

BACKGROUND: The outcomes after kidney transplantation (KT), including access, wait time, and other issues around the globe, have been studied. However, issues do vary from one country to another. METHODS: We obtained data from several countries from North America, South America, Europe, Asia, and Australia, including the number of patients awaiting KT from 2015, transplant rate per million population (pmp), proportion of living donor and deceased donor (LD/DD) KT, and posttransplant survival. We also sought opinions on key difficulties faced by each of these countries with respect to KT and long-term survival. RESULTS: Variation in access to KT across the globe was noted. Countries with the highest rates of KT pmp included the United States (79%) and Spain (71%). A higher proportion of LD transplants was noted in Japan (93%), India (85%), Singapore (63%), and South Korea (63%). A higher proportion of DD KTs was noted in Spain (90%), Brazil (90%), France (85%), Italy (85%), Finland (85%), Australia-New Zealand (80%), and the United States (77%). The 5-y graft survival for LD was highest in South Korea (95%), Singapore (94%), Italy (93%), Finland (93%), and Japan (93%), whereas for DD, it was South Korea (93%), Italy (88%), Japan (86%), and Singapore (86%). The common issues surrounding KTs are access and a limited number of LDs and DDs. Key issues identified for long-term survival were increasing age of donors and recipients, higher recipient comorbidity, and posttransplant events, such as alloimmune injury to the kidney, infection, cancer, and suboptimal adherence to therapy. CONCLUSIONS: A unified approach is necessary to improve issues surrounding KT as the demand continues to increase.

Act Together and Act Now to Overcome Gender Disparity in Organ Transplantation.

Gender disparity refers to the unequal treatment or a perception of individuals based on their gender and arises from differences in socially constructed gender roles. In the field of transplantation, gender inequality arises at different stages, affecting access to medical care, donation practices, and posttransplant followup care. Gender disparity in transplantation is not limited to any geographic region but is thought to be more prevalent in developing nations. An unusually high number of female donations with relatively fewer female recipients is not only attributable to the low economy but a congregation of medical, social, cultural, and psychological factors. Gender disparities can also be shown in transplant-related professional societies. This review highlights the complexities of spousal donation and vulnerability of women, especially in the developing world. There is a growing need to further modify transplant policies to tackle gender disparities, especially in living related donation. Systematic research in the context of gender-related concerns in transplantation will further aid in understanding the complexities and formulating policies for eliminating gender disparities. Gender disparity is a global problem and not merely limited to transplantation.

Are Differences in Living Kidney Donation Rates a Sex or a Gender Disparity?

Sex-disaggregated data reveal significant disparities in living kidney donation, with more female than male living kidney donors in most countries and proportions over 60% in some countries. We summarize the present state of knowledge with respect to the potential drivers of this disparity and argue that it is primarily driven by gender-related factors. First, we present the differences between sex and gender and then proceed to summarize the potential medical reasons that have been proposed to explain why males are less likely to be living kidney donors than females, such as the higher prevalence of kidney failure in males. We then present counterarguments as to why biological sex differences are not enough to explain lower living kidney donation among males, such as a higher prevalence of chronic kidney disease among females, which could affect donation rates. We argue that gender differences likely provide a better explanation as to why there are more women than men living kidney donors and explore the role of economic and social factors, as well as gender roles and expectations, in affecting living kidney donation among both men and women. We conclude with the need for a gender analysis to explain this complex psychosocial phenomenon in living kidney donation.

A Multicenter Retrospective Cohort Study on Management Protocols and Clinical Outcomes After ABO-incompatible Kidney Transplantation in India.

BACKGROUND: There is no robust evidence-based data for ABO-incompatible kidney transplantation (ABOiKT) from emerging countries. METHODS: Data from 1759 living donor ABOiKT and 33 157 ABO-compatible kidney transplantations (ABOcKT) performed in India between March 5, 2011, and July 2, 2022, were included in this retrospective, multicenter (n = 25) study. The primary outcomes included management protocols, mortality, graft loss, and biopsy-proven acute rejection (BPAR). RESULTS: Protocol included rituximab 100 (232 [13.18%]), 200 (877 [49.85%]), and 500 mg (569 [32.34%]); immunoadsorption (IA) (145 [8.24%]), IVIG (663 [37.69%]), and no induction 200 (11.37%). Mortality, graft loss, and BPAR were reported in 167 (9.49%), 136 (7.73%), and 228 (12.96%) patients, respectively, over a median follow-up of 36.3 mo. In cox proportional hazard model, mortality was higher with IA (hazard ratio [HR]: 2.53 [1.62-3.97]; P < 0.001), BPAR (HR: 1.83 [1.25-2.69]; P = 0.0020), and graft loss (HR: 1.66 [1.05-2.64]; P = 0.0310); improved graft survival was associated with IVIG (HR: 0.44 [0.26-0.72]; P = 0.0010); higher BPAR was reported with conventional tube method (HR: 3.22 [1.9-5.46]; P < 0.0001) and IA use (HR: 2 [1.37-2.92]; P < 0.0001), whereas lower BPAR was reported in the prepandemic era (HR: 0.61 [0.43-0.88]; P = 0.008). Primary outcomes were not associated with rituximab dosing or high preconditioning/presurgery anti-A/anti-B titers. Incidence of overall infection 306 (17.39%), cytomegalovirus 66 (3.75%), and BK virus polyoma virus 20 (1.13%) was low. In unmatched univariate analysis, the outcomes between ABOiKT and ABOcKT were comparable. CONCLUSIONS: Our largest multicenter study on ABOiKT provides insights into various protocols and management strategies with results comparable to those of ABOcKT.

I-JAMM-(I): A survey providing an insight into the practices of isoagglutinin titration in ABO incompatible kidney and liver transplantation.

BACKGROUND AND OBJECTIVES: ABO-incompatible transplantations allow patients to receive timely transplants. Isoagglutinin titration to ascertain levels of incompatible antibodies in the recipient is important in determining patient selection and transplant survivability. To find out the prevalent trends in India, the largest, first of its kind survey was carried out among the transplant centers regarding their practices in isoagglutinin titration. METHODS: The survey was drafted by a working group of Transfusion and Transplant Immunology specialists from six different centers. Data was obtained via the use of an online questionnaire. RESULTS: Results were categorized into four categories, Hospital information, Titration methodology, Role of transfusion specialists and cut-off titers. Most centers had a well-established solid-organ transplant program with considerable number of ABO-incompatible transplantations. Most centers performed isoagglutinin titration in Transfusion Medicine department. Column Agglutination Technique (CAT) was the most common method, using EDTA blood samples and freshly-prepared in-house pooled cells. Most centers had a turn-around time of less than 12 h. While the policy for ascertaining baseline and threshold titers is well-defined in ABO-incompatible renal transplants, variations from center to center still exist for ABO-incompatible liver transplants. Most centers required a Transfusion Medicine consultation for the patients before such transplants. CONCLUSION: With increasing ABO-incompatible kidney and liver transplants across the country, the role of Transfusion medicine specialists has become vital in pre-conditioning regimes enabling the viability and success of such transplants. This was a unique survey that provided a snapshot of current trends and practices of isoagglutinin titration for ABO-incompatible transplants in India.

De novo Donor-specific Anti-human Leukocyte Antigen Antibody and Its Outcome in Pediatric Renal Transplant Recipients: A Single-center Experience in India.

Development of de novo donor-specific anti-HLA antibody (dnDSA) is associated with poor graft survival in adults. However, there is a paucity of data about its prevalence and outcome in Indian children. We retrospectively assessed the proportion and spectrum of dnDSA and its outcome on antibody-mediated rejection (ABMR) and graft function. Children ≤18 years who were transplanted between November 2016 and October 2019 were included in this study. Pretransplant donor-specific antibody (DSA) was screened by complement-dependent cytotoxicity, flow cytometry crossmatch, and single antigen bead (SAB) class I and II by Luminex platform. Either antithymocyte globulin or basiliximab was used as induction. Tacrolimus, mycophenolate, and prednisolone were used for the maintenance of immunosuppression. SAB screening was done at 1, 3, 6 months, and yearly in seven children and at the time of acute graft dysfunction in eight. Mean fluorescence intensity ≥1000 was considered positive. Protocol biopsies were done at 3, 6, and 12 months and annually thereafter in seven children. Fifteen children, all males with a median age (interquartile range) of 13 years (11; 15.5) were analyzed. Only one child had pretransplant DSA who developed dnDSA posttransplant. Overall, 8 (53%) developed dnDSA over a median follow-up of 18 months. Seven (87%) had Class II, one Class I and 3 (37%) both Class I and II. Six had dQ and two had DR. All children with dnDSA had ABMR, of these two had subclinical rejection. DSAs persisted despite treatment, though graft function improved. Children with DSA and ABMR had lower graft function than those without DSA. The proportion of dnDSA was high in our study, majority against DQ. The detection of dnDSA prompted early diagnosis and treatment of ABMR.

Parvovirus in Kidney Transplant Recipients: A Single-Center Experience.

OBJECTIVES: Parvovirus testing is not done in routine clinical practice; thus, it is possible that reported parvovirus cases are just the tip of the iceberg of total prevalence. We present a single-center retrospective analysis of 22 events of parvovirus B19 anemia in 20 renal transplant recipients, among which 2 patients had recurrence. MATERIALS AND METHODS: For this descriptive analytical study, parvovirus B19 disease was defined as parvovirus infection (detection by real-time polymerase chain reaction) in the presence of anemia with clinical symptoms or bone marrow biopsy findings consistent with the diagnosis. Study duration was 18 months, from June 2021 through December 2022, and patients were enrolled from a single center. RESULTS: All patients detected with the virus had received induction with thymocyte globulin and were on standard triple drug immunosuppression. Mean age was 32 ± 12 years with median time to diagnosis of 2 months after transplant. Anemia was observed in all patients with mean hemoglobin level at presentation of 6.02 ± 1.28 g/dL. Creatinine at presentation was 1.49 mg/dL (interquartile range, 0.92-2.69 mg/dL). The most common presentation was asymptomatic patient with evaluation for anemia. During therapy, the highest median creatinine level was 2.0 mg/dL (interquartile range, 1.38-3.2 mg/dL), which was significantly higher than that at presentation (P < .018). After therapy, median creatinine level was 1.3 mg/dL, which was not significantly higher than the baseline level, demonstrating a mostly transient graft dysfunction. CONCLUSIONS: Parvovirus B19 is a relatively underreported disease in renal transplant recipients, with patients presenting with anemia and the disease causing transient graft dysfunction. Parvovirus B19 infection responds well to a decrease in immunosuppression and intravenous immunoglobulin therapy.

A Comparative Analysis of Chikungunya in Kidney Transplant Recipients Compared With the General Population: A Multicenter, Retrospective, Cohort Study From India.

OBJECTIVES: Chikungunya is an arboviral illness, with patients presenting with fever, arthralgias, and myalgias. Outbreaks have occurred in tropical regions, and the virus is now endemic to many tropics, including South Asia, with India contributing a large part of the global burden. The presentation and long-term effects on transplant recipients are largely unknown. MATERIALS AND METHODS: In this retrospective analytical study, we compared chikungunya infection in 44 kidney transplant recipients from multiple centers in India and 34 patients from the general population. Data were collected from medical records and patient recall. RESULTS: Differences in presentation were remarkable between the 2 groups, with significantly lower incidence of musculoskeletal symptoms on presentation in transplant recipients compared with the general population. The incidence of acute graft dysfunction was 17.08% in transplant recipients, with return to baseline at the end of 1 month. Acute symptomatology resolved in transplant recipients within 1 month, and insignificant chronic symptoms were reported after 3 months. CONCLUSIONS: Chikungunya in kidney transplant recipients is markedly different from that of the general population, with significantly lower incidence of musculoskeletal symptoms such as arthralgias. The infection caused acute graft dysfunction, but no long-term sequelae were shown at the end of 1 year.

Kidney paired donation in developing countries: A global perspective.

Purpose of review: We review the key principles of kidney paired donation (KPD) and discuss the status and unique considerations for KPD in developing countries. Recent findings: Despite the advantages of KPD programs, they remain rare among developing nations, and the programs that exist have many differences with those of in developed countries. There is a paucity of literature and lack of published data on KPD from most of the developing nations. Expanding KPD programs may require the adoption of features and innovations of successful KPD programs. Cooperation with national and international societies should be encouraged to ensure endorsement and sharing of best practices. Summary: KPD is in the initial stages or has not yet started in the majority of the emerging nations. But the logistics and strategies required to implement KPD in developing nations differ from other parts of the world. By learning from the KPD experience in developing countries and adapting to their unique needs, it should be possible to expand access to KPD to allow more transplants to happen for patients in need world-wide.

Hematopoietic cell-based and non-hematopoietic cell-based strategies for immune tolerance induction in living-donor renal transplantation: A systematic review.

INTRODUCTION: Despite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal is the ultimate goal of kidney transplantation, and is made possible by the induction of immunological tolerance. The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism-based and non-chimerism-based. The impact of these strategies on transplant outcomes, including acute rejection, allograft function and survival, cost, and immune monitoring, will also be discussed. MATERIALS AND METHODS: Databases such as PubMed, Scopus, and Web of Science, as well as additional online resources such as EBSCO, were exhaustively searched. Adult living-donor kidney transplant recipients who developed chimerism-based tolerance after concurrent bone marrow or hematopoietic stem cell transplantation or those who received non-chimerism-based, non-hematopoietic cell therapy using mesenchymal stromal cells, dendritic cells, or regulatory T cells were studied between 2000 and 2021. Individual sources of evidence were evaluated critically, and the strength of evidence and risk of bias for each outcome of the transplant tolerance study were assessed. RESULTS: From 28,173 citations, 245 studies were retrieved after suitable exclusion and duplicate removal. Of these, 22 studies (2 RCTs, 11 cohort studies, 6 case-control studies, and 3 case reports) explicitly related to both interventions (chimerism- and non-chimerism-based immune tolerance) were used in the final review process and were critically appraised. According to the findings, chimerism-based strategies fostered immunotolerance, allowing for the safe withdrawal of immunosuppressive medications. Cell-based therapy, on the other hand, frequently did not induce tolerance except for minimising immunosuppression. As a result, the rejection rates, renal allograft function, and survival rates could not be directly compared between these two groups. While chimerism-based tolerance protocols posed safety concerns due to myelosuppression, including infections and graft-versus-host disease, cell-based strategies lacked these adverse effects and were largely safe. There was a lack of direct comparisons between HLA-identical and HLA-disparate recipients, and the cost implications were not examined in several of the retrieved studies. Most studies reported successful immunosuppressive weaning lasting at least 3 years (ranging up to 11.4 years in some studies), particularly with chimerism-based therapy, while only a few investigators used immune surveillance techniques. The studies reviewed were often limited by selection, classification, ascertainment, performance, and attrition bias. CONCLUSIONS: This review demonstrates that chimerism-based hematopoietic strategies induce immune tolerance, and a substantial number of patients are successfully weaned off immunosuppression. Despite the risk of complications associated with myelosuppression. Non-chimerism-based, non-hematopoietic cell protocols, on the other hand, have been proven to facilitate immunosuppression minimization but seldom elicit immunological tolerance. However, the results of this review must be interpreted with caution because of the non-randomised study design, potential confounding, and small sample size of the included studies. Further validation and refinement of tolerogenic protocols in accordance with local practice preferences is also warranted, with an emphasis on patient selection, cost ramifications, and immunological surveillance based on reliable tolerance assays.

NOTTO Guidelines for Vaccine Induced Thrombotic Thrombocytopenia in Organ Donation and Transplantation.

From the context of organ donation, COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is important as there is an ethical dilemma in utilizing versus discarding organs from potential donors succumbing to VITT. This consensus statement is an attempt by the National Organ and Tissue Transplant Organization (NOTTO) apex technical committees India to formulate the guidelines for deceased organ donation and transplantation in relation to VITT to help in appropriate decision making. VITT is a rare entity, but a meticulous approach should be taken by the Organ Procurement Organization's (OPO) team in screening such cases. All such cases must be strictly notified to the national authorities like NOTTO, as a resource for data collection and ensuring compliance withprotocols in the management of adverse events following immunization. Organs from any patient who developed thrombotic events up to 4 weeks after adenoviral vector-based vaccination should be linked to VITT and investigated appropriately. The viability of the organs must be thoroughly checked by the OPO, and the final decision in relation to organ use should be decided by the expert committee of the OPO team consisting of a virologist, a hematologist, and atreating team. Considering the organ shortage, in case of suspected/confirmed VITT, both clinicians and patients should consider the risk-benefit equationbased on available experience, and an appropriate written informed consent of potential recipients and family members should be obtained before transplantation of organs from suspected or proven VITT donors.

COVID-19: Clinical Course and Outcome of hospitalized Hemodialysis Patients: Single-center Experience.

BACKGROUND: There is a paucity of data regarding the consequences of coronavirus disease 2019 (COVID-19) infection in patients with maintenance hemodialysis (MHD). Our objective was to identify the clinical manifestations and prognostic factors and to assess the impact of treatment schemes on the outcomeMaterials and methods: Here we present retrospectively collected data from medical records of patients on MHD hospitalized with COVID-19 infection from 1st June to 30th November 2020Result: Around 69 patients were admitted with a median age of 51 years. About 81% had hypertension, 41% had diabetes, and 24% had body mass index (BMI) ≥ 23 kg/m2 . Of all who died, 73.33% had dialysis vintage of <12 months (p = 0.06). Common presenting symptoms were fatigue (67%), fever (58%), cough (42%), and dyspnea (35%). Milder, severe, and critical disease was found in 35, 45, and 20% of patients, respectively. About 54 patients were living 4 weeks after discharge. Around 15 patients died, that includes all who received invasive ventilatory support. Nonsurvivors were older and had lower oxygen saturation on admission, lower hemoglobin (Hb), and worst lactate dehydrogenase (LDH), interleukin (IL)-6, and D-dimer values than survivors, which were statistically significant. Use of remdesivir and anticoagulant improves chances of survival (p-value 0.035 and 0.034, respectively) Conclusion: About one-third of patients had mild disease. Those with critical disease displayed high mortality. Older age, male gender, short dialysis vintage, lower oxygen saturation on admission, anemia, leucocytosis, higher inflammatory markers [except C-reactive protein (CRP)], bilateral lung opacity, and requirement of the mechanical ventilator are poor prognostic factors. CRP, ferritin, and lymphopenia are not good prognostic markers unlike in the general population. These findings need to be verified in larger cohorts.

Molecular Epidemiology of Rifampicin-Resistant Mycobacterium tuberculosis by GeneXpert MTB/RIF Assay in Renal Transplant Recipients: A Single-Center Experience.

OBJECTIVES: There are scarce data on the incidence and resistance pattern of rifampicin-resistant Mycobacterium tuberculosis among kidney transplant recipients. MATERIALS AND METHODS: This is a retrospective, single- center study of kidney transplantrecipients suspected of M. tuberculosis infection. The GeneXpert assay we used detected mutations in the rpoB gene that confer rifampicin resistance using 5 overlapping probes (A, B, C, D, and E). The probes can detect mutations in the codons 507 to 511 (probe A), 511 to 518 (probe B), 518 to 523 (probe C), 523 to 529 (probe D), and 529 to 533 (probe E).We also detailed the treatment protocol and outcomes of kidney transplantrecipients infected with rifampicin-resistant M. tuberculosis. RESULTS: In total, 2700 samples were processed during the period from October 2018 to February 2022 with successful results in 2640 samples (97.04%). One hundred and ninety (7.19%) samples were positive for M.tuberculosis, and rifampicin resistance was detected in 12 (0.45%) cases (11 pulmonary, 1 genitourinary). The most common rpoB mutation was located in the region of probe E (75.0%), followed by probe A (16.6%) and in 1 combination probe DE (8.33%). The rpoB mutations were not observed in probe B and probe C. Six patients received bedaquiline-based treatmentfor a short course of 11 months, whereas the other 6 patients required a long course of 18 to 20 months. Three patients died, 2 were lost to follow-up, and 7 were cured. During treatment, 4 patients experienced acute rejection, and 1 graft loss was reported. CONCLUSIONS: We report for the first time the incidence and pattern of rifampicin resistance among kidney transplant recipients with tuberculosis infection. Further investigations are required for exploring the molecular and clinical phenotypes.

Social Media and Organ Donation: Pros and Cons.

Shortage of organ donors is the most important obstacle standing in the way of lifesaving organ transplantation in a myriad of patients suffering from end-stage organ failure. It is vital that the transplant societies and associated appropriate authorities develop strategies to overcome the unmet needs for organ donation. The power of prominent social media (SoMe) platforms such as Facebook, Twitter, and Instagram, which reach millions of people, can increase awareness, provide education, and may ameliorate the pessimism toward organ donation among the general population. Additionally, public solicitation of organs may be helpful for waitlisted candidates for organ transplantation, who cannot find a suitable donor among near relations. However, the use of SoMe for organ donation has several ethical issues. This review attempts to highlight the advantages and limitations of using social media in the context of organ donation for transplantation. Some suggestions on the best utilization of social media platforms for organ donation while balancing ethical considerations have been highlighted here.

International Practices on COVID-19 Vaccine Mandates for Transplant Candidates.

Background: The coronavirus disease 2019 (COVID-19) pandemic created unprecedented challenges for solid organ transplant centers worldwide. We sought to assess an international perspective on COVID-19 vaccine mandates and rationales for or against mandate policies. Methods: We administered an electronic survey to staff at transplant centers outside the United States (October 14, 2021-January 28, 2022) assessing the reasons cited by transplant centers for or against implementing a COVID-19 vaccine mandate. Each responding center was represented once in the analysis. Results: Respondents (N=90) represented 27 countries on five continents. Half (51%) of responding transplant center representatives reported implementing a COVID-19 vaccine mandate, 38% did not, and 12% were unsure. Staff at centers implementing a vaccine mandate cited efficacy of pretransplant vaccination versus post-transplant vaccination, importance for public health, and minimizing exposure of other patients as rationale for the mandate. Of centers with a mandate, the majority (81%) of the centers mandate vaccination regardless of prior SARS-CoV-2 infection status and regardless of prevaccination spike-protein antibody titer or other markers of prior infection. Only 27% of centers with a vaccine mandate for transplant candidates also extended a vaccine requirement to living donor candidates. Centers not implementing a vaccine mandate cited concerns for undue pressure on transplant candidates, insufficient evidence to support vaccine mandates, equity, and legal considerations. Conclusions: The approach to pretransplant COVID-19 vaccination mandate policies at international transplant centers is heterogeneous. International transplant centers with a vaccine mandate were more willing to extend vaccine requirements to candidates' support persons, cohabitants, and living donors. Broader stakeholder engagement to overcome vaccine hesitancy across the world is needed to increase the acceptance of pretransplant COVID-19 vaccination to protect the health of transplant patients.