Challenging boundaries: Organ transplants from donors with Listeria central nervous system infections.

Pretransplant mortality rates in the US remain high and are connected to effective organ donation and utilization. Thus, there is a need to maximize the utilization of available donors. In some cases, this has been safely achieved using organs from donors with infectious complications. For example, several studies describe the use of organs from donors with bacterial meningitis due to pathogens such as Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenza, and Escherichia coli, with good outcomes. Listeria is an aerobic and facultatively anaerobic, nonspore-forming, Gram-positive rod that can affect the central nervous system, causing meningitis and meningoencephalitis. Due to its virulence, ability to cause intracellular infection, and lack of clinical data, people dying with listeria may not be evaluated for organ donation, may not have organs recovered, or may have their organs recovered but not transplanted. Herein, we describe the outcomes of 7 solid organ transplant recipients who received organs from 2 donors with Listeria monocytogenes central nervous system infection.

Psychosocial characteristics of potential and actual living kidney donors.

The psychosocial assessment is an essential component of the living kidney donor (LKD) evaluation. However, it remains uncertain how specific psychosocial factors impact LKD eligibility. We performed a retrospective chart review of LKD candidates who initiated the evaluation process and who had completed a required, in-person licensed social work (LSW) visit. LSW notes were reviewed for frequency of psychosocial factors that may impact the success of LKD candidate approval by the selection committee. 325 LKD candidates were included in the study: 104 not-approved and 221 approved. Not-approved LKD candidates were more likely to receive a negative family reaction to wanting to donate than approved LKD candidates (8.7% vs 1.4%, p < 0.01). On multivariate analysis, Black race, history of psychiatric illness, highest level of education being high school, and high psychosocial risk score assignment were all associated with a lower odds ratio of being approved. The majority of not-approved LKD candidates were disqualified for medical reasons (N = 76, 73.1%). In conclusion, psychosocial factors impact donation even after LKD candidates make it to an in-person evaluation.

Hereditary thrombotic thrombocytopenic purpura acquired through liver transplantation: A case report.

A 62-year-old received orthotopic liver transplantation. Three weeks later, thrombotic microangiopathy developed. Testing revealed thrombotic thrombocytopenic purpura (TTP) characterized by low ADAMTS13 (A Disintegrin-like Metallopeptidase with ThromboSpondin type 1 motif 13) activity and no inhibitor of ADAMTS13 protein. Retrospective attainment of donor records revealed a TTP diagnosis, presumably hereditary TTP (hTTP), as an ADAMTS13 protein inhibitor was not mentioned. As the grafted liver does not produce ADAMTS13 protein, the recipient now functionally has hTTP and will likely need plasma transfusions indefinitely. While hTTP is extremely rare, it should be considered a contraindication to liver donation outside of exceptional circumstances. If a potential liver donor has TTP listed on medical history, attempts should be made to determine whether it is autoimmune or hereditary. An accurate medical history is critical as it is the only reliable way to identify hTTP, as outside of acute exacerbations of TTP, donors with hTTP can have normal laboratory values, including normal hemoglobin, platelets, and renal function.

The minimum weight and age of kidney donors: en bloc kidney transplantation from preterm neonatal donors weighing less than 1.2 kg to adult recipients.

En bloc kidney transplantation (EBKT) to adults from preterm neonates following donation after circulatory death has not been described in the literature. We report 2 successful cases of EBKT from preterm neonatal donation after circulatory death donors weighing <1.2 kg to adult recipients. The first case was a preterm female infant born at 29 weeks' gestational age, weighing 1.07 kg. The recipient was a 34-year-old woman weighing 75 kg. At the 9-month follow-up, the patient demonstrated excellent graft function with a creatinine concentration of 1.48 mg/dL. The second donor was a preterm female infant born at 29 weeks and 5 days' gestation, weighing 1.17 kg. The recipient was a 25-year-old woman weighing 46 kg. By 5 months post surgery, the serum creatinine level had gradually decreased to 1.47 mg/dL. In our experience, EBKT from preterm neonates <30 weeks' gestation and weighing <1.2 kg has demonstrated acceptable short- to medium-term results.

Lithium and the living kidney donor: Science or stigma?

Nearly 10 000 people are removed from the kidney transplant waiting list each year either due to becoming too ill for transplant or due to death. Live donor kidney transplant (LDKT) provides superior outcomes and survival benefit relative to deceased donor transplant, but the number of LDKT has decreased over the past few years. Therefore, it is of paramount importance that transplant centers employ evaluation processes that safely maximize LDKT. Decisions about donor candidacy should be based on the best available data, rather than on processes prone to bias. Here, we examine the common practice of declining potential donors based solely on treatment with lithium. We conclude that the risk of end-stage renal disease related to lithium treatment is comparable to other generally accepted risks in LDKT. We present this viewpoint to specifically challenge the carte blanche exclusion of individuals taking lithium and highlight the importance of using the best available data relevant to any risk factor, rather than relying on biases, when evaluating potential living kidney donors.

The living donor evaluation as a life-saving event.

BACKGROUND: As a population, living kidney donors have a longer life expectancy than the general population. This is generally thought to be an artifact of selection, as only healthy individuals are allowed to donate, and the operative mortality and risk of subsequent renal failure are very low. However, there may also be an additional benefit to the process, as the donor evaluation may uncover an early occult cancer or a potentially serious medical problem. While these problems may preclude donation, they may be lifesaving, as they are likely to be diagnosed and treated before the donor develops symptoms. PATIENTS AND METHODS: We looked at the incidence of occult cancer and other previously undiagnosed medical problems including renal disease, diabetes, hypertension, cardiac disease, and hepatitis C, in individuals volunteering to become a kidney donor at our center who proceeded with the evaluation between January 1, 1996 and May 31, 2011. RESULTS: Of 4088 potential donors, 19 (.46%) were discovered to have an unsuspected cancer, and 286 (7%) were found to have a previously undiagnosed medical problem. CONCLUSIONS: The living donor evaluation may lead to the early diagnosis of a life-threatening illness. This should be considered as one of the potential benefits of living donation.

Living kidney donor evaluation is associated with early identification of life-changing diagnoses in potentially healthy donor candidates.

BACKGROUND: In order to ensure eligibility for living kidney donation, donor candidates undergo a thorough medical evaluation. This process might reveal hitherto undetected medical conditions, leading to refusal of the kidney donor candidate. Detection of such conditions may, however, also have a lifesaving effect. We report on 13 years of data from our living donor transplantation program on kidney donor candidates who were diagnosed with major medical conditions during evaluation. MATERIALS AND METHODS: We performed a retrospective analysis of living kidney donor candidates who attended our transplant center between January, 2007 and December, 2019. The main focus was on newly diagnosed medical conditions that required immediate medical attention and their prognostic significance. RESULTS: Of the 436 donor candidates who were evaluated for living kidney donation at our transplant center, 192 (44%) were accepted, while 244 (56%) were excluded from donation. Interestingly, 81 (33.1%) of the ineligible donor candidates were newly diagnosed as having a medical condition that required immediate attention. While 45 (18.5%) candidates were newly diagnosed with diabetes or prediabetes, 12 (4.9%) candidates had hitherto undetected malignancies, 10 candidates (4.1%) cardiac disease, five (2.0%) hypertension with end-organ damage, and four (1.6%) suffered from kidney disease. The remaining four candidates (1.6%) were diagnosed with gastrointestinal diseases, and one candidate (.4%) had an endocrine disorder. CONCLUSION: A comprehensive evaluation process for living kidney donation facilitates the identification of life-changing diagnoses in a significant proportion of candidates and secures immediate medical attention.

Does donor treatment with inotropes and/or vasopressors impact post-transplant outcomes?

PURPOSE: The purpose was to evaluate the effects of the most commonly used cardiac donor inotropes/vasopressors on subsequent post-heart transplant survival. METHODS: Adult heart transplant recipients from January 2000 to June 2022 were identified in the United Network for Organ Sharing (UNOS) database. Exclusion criteria included: multiorgan transplants, donor age < 15, and recipient age < 18. Donors receiving vasoactive medications at the time of procurement were compared to donors not receiving these medications. Those on vasoactive medications were stratified by medication: phenylephrine, dopamine, dobutamine, norepinephrine and epinephrine, the combination of these agents, and the concomitant administration of vasopressin with any single agent alone or in combination. The primary area of interest was short-and-long-term survival. Survival at 30 days, 1 year, and long-term (Median = 13.6 years) was compared using logistic and Cox models to quantify survival endpoints. RESULTS: A total of 45,198 donors met inclusion criteria and had data on the use of vasoactive agents available. Mean donor age was 32.3 years with 71% male. Vasoactive medications and potential combinations included phenylephrine in 8156 donors (18.0%), dopamine in 9550 (21.1%), dobutamine in 718 (1.6%), epinephrine in 332 (.73%), and norepinephrine in 4854 (10.7%). A total of 25,856 donors (57.2%) were receiving vasopressin at the time of procurement. There was no impact of donor inotropes on 30-day survival. Donors receiving one inotrope and no vasopressin were associated with increased 1 year mortality (OR 1.14; p = .021), as were donors receiving 2+ inotropes and no vasopressin (OR 1.26; p = .006). For individual agents, 1 year mortality was increased for dopamine (OR 1.11; p = .042) and epinephrine (OR 1.59; p = .004). CONCLUSIONS: There is no difference in heart transplant recipient survival at 30 days when the donor is receiving inotropes without vasopressin at the time of procurement. Inotropic support without vasopressin is associated with greater 1 year mortality. The impact of donor inotropic support on long term heart transplant survival, and the interaction with vasopressin warrants further study.

Sex-specific genetic modifiers identified susceptibility of cold stored red blood cells to osmotic hemolysis.

BACKGROUND: Genetic variants have been found to influence red blood cell (RBC) susceptibility to hemolytic stress and affect transfusion outcomes and the severity of blood diseases. Males have a higher susceptibility to hemolysis than females, but little is known about the genetic mechanism contributing to the difference. RESULTS: To investigate the sex differences in RBC susceptibility to hemolysis, we conducted a sex-stratified genome-wide association study and a genome-wide gene-by-sex interaction scan in a multi-ethnic dataset with 12,231 blood donors who have in vitro osmotic hemolysis measurements during routine blood storage. The estimated SNP-based heritability for osmotic hemolysis was found to be significantly higher in males than in females (0.46 vs. 0.41). We identified SNPs associated with sex-specific susceptibility to osmotic hemolysis in five loci (SPTA1, KCNA6, SLC4A1, SUMO1P1, and PAX8) that impact RBC function and hemolysis. CONCLUSION: Our study established a best practice to identify sex-specific genetic modifiers for sexually dimorphic traits in datasets with mixed ancestries, providing evidence of different genetic regulations of RBC susceptibility to hemolysis between sexes. These and other variants may help explain observed sex differences in the severity of hemolytic diseases, such as sickle cell and malaria, as well as the viability of red cell storage and recovery.

Rethinking incompatibility in kidney transplantation.

Donor/recipient incompatibility in kidney transplantation classically refers to ABO/HLA-incompatibility. Kidney paired donation (KPD) was historically established to circumvent ABO/HLA-incompatibility, with the goal of identifying ABO/HLA-compatible matches. However, there is a broad range of donor factors known to impact recipient outcomes beyond ABO/HLA-incompatibility, such as age and weight, and quantitative tools are now available to empirically compare potential living donors across many of these factors, such as the living donor kidney donor profile index (LKDPI). Moreover, the detrimental impact of mismatch at other HLA antigens (such as DQ) and epitope mismatching on posttransplant outcomes has become increasingly recognized. Thus, it is time for a new paradigm of incompatibility that considers all of these risks factors together in assessing donor/recipient compatibility and the potential utility for KPD. Under this new paradigm of incompatibility, we show how the LKDPI and other tools can be used to identify donor/recipient incompatibilities that could be improved through KPD, even for those with a traditionally "compatible" living donor.

Challenges encountered in conducting donor-based research: Lessons learned from the Donor Heart Study.

Solid organ transplantation continues to be constrained by a lack of suitable donor organs. Advances in donor management and evaluation are needed to address this shortage, but the performance of research studies in deceased donors is fraught with challenges. Here we discuss several of the major obstacles we faced in the conduct of the Donor Heart Study-a prospective, multi-site, observational study of donor management, evaluation, and acceptance for heart transplantation. These included recruitment and engagement of participating organ procurement organizations, ambiguities related to study oversight, obtaining authorization for donor research, logistical challenges encountered during donor management, sustaining study momentum, and challenges related to study data management. By highlighting these obstacles encountered, as well as the solutions implemented, we hope to stimulate further discussion and actions that will facilitate the design and execution of future donor research studies.

Utilization and outcomes of deceased donor SARS-CoV-2-positive organs for solid organ transplantation in the United States.

Coronavirus disease-19 has had a marked impact on the transplant population and processes of care for transplant centers and organ allocation. Several single-center studies have reported successful utilization of deceased donors with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tests. Our aims were to characterize testing, organ utilization, and transplant outcomes with donor SARS-CoV-2 status in the United States. We used Scientific Registry of Transplant Recipients data from March 12, 2020 to August 31, 2021 including a custom file with SARS-CoV-2 testing data. There were 35 347 donor specimen SARS-CoV-2 tests, 77.5% upper respiratory samples, 94.6% polymerase chain reaction tests, and 1.2% SARS-CoV-2-positive tests. Donor age, gender, history of hypertension, and diabetes were similar by SARS-CoV-2 status, while positive SARS-CoV-2 donors were more likely African-American, Hispanic, and donors after cardiac death (p-values <.01). Recipient demographic characteristics were similar by donor SARS CoV-2 status. Adjusted donor kidney discard (odds ratio = 2.08, 95% confidence interval [CI] 1.66-2.61) was higher for SARS-CoV-2-positive donors while donor liver (odds ratio = 0.44, 95% CI 0.33-0.60) and heart recovery (odds ratio = 0.44, 95% CI 0.31-0.63) were significantly reduced. Overall post-transplant graft survival for kidney, liver, and heart recipients was comparable by donor SARS-CoV-2 status. Cumulatively, there has been significantly lower utilization of SARS-CoV-2 donors with no evidence of reduced recipient graft survival with variations in practice over time.

Impact of ex vivo lung perfusion on brain-dead donor lung utilization: The French experience.

Ex vivo lung perfusion (EVLP) is a valuable method for expanding the lung donor pool. Its indications currently differ across centers. This national retrospective cohort study aimed to describe the profile of donors with lungs transplanted after EVLP and determine the effectiveness of EVLP on lung utilization. We included brain-dead donors with at least one lung offered between 2012 and 2019 in France. Lungs transplanted without or after EVLP were compared with those that were rejected. Donor group phenotypes were determined with multiple correspondence analysis (MCA). The association between donor factors and lung transplantation was assessed with a multivariable multinomial logistic regression. MCA revealed that donors whose lungs were transplanted after EVLP had profiles similar to the donors whose lungs were declined and quite different from those of donors with lungs transplanted without EVLP. Donor predictors of graft nonuse included age ≥50 years, smoking history, PaO2 /FiO2 ratio ≤300 mmHg, abnormal chest imaging, and purulent secretions. EVLP increased utilization of lungs from donors with a smoking history, PaO2 /FiO2 ratio ≤300 mmHg, and abnormal chest imaging.

Evaluation of donor heart for transplantation.

Cardiac transplantation is considered the gold-standard treatment option for patients suffering from end-stage heart failure refractory to maximum medical therapy. A major determinant of graft function and recipient survival is a comprehensive evaluation of the donor allograft. Challenges arise when designing and implementing an evidence-based donor evaluation protocol due to the number of influential donor-specific characteristics and the complex interactions that occur between them. Here, we present our systematic approach to donor evaluation by examining the impact that relevant donor variables have on graft function and recipient outcomes.

Expanding donor age in liver transplantation using liver grafts from nonagenarian donors.

INTRODUCTION: Satisfactory outcomes in a series of liver transplantations (LT) with octogenarian liver grafts have been reported, as well as several cases of LT using nonagenarian liver grafts with short follow-up. METHODS: From October 2013 to December 2019, we performed 426 LT. Six LTs used nonagenarian livers (case group) and 49 used octogenarian livers (control group). A comparative analysis was performed between groups. Median donor age was significantly higher in the nonagenarian group than in the octogenarian group (90.6 years versus 83.4 years; (P < .001). There was a significant difference in LT indications (P = .026) between the groups, but not in perioperative recipient variables, morbidity, or mortality. The 1-, 3-, and 5-year patient survival rates were 67.7% in the recipients of nonagenarian livers and 85.7%, 78.0%, and 74.4%, respectively, in the recipients of octogenarian livers (P = .631). The 1-, 3-, and 5-year graft survival rates were 66.7% in the recipients of nonagenarian livers and 81.3%, 73.8%, and 70.3%, respectively, in the recipients of octogenarian livers (P = .745). CONCLUSIONS: The results of LT with nonagenarian liver grafts are not significantly different from those obtained with octogenarian donors, taking into consideration the small sample size and careful selection of donors and adequate donor-recipient matching.

Relevance of deceased donor proteinuria for kidney transplantation: A comprehensive national cohort study.

PURPOSE: Proteinuria is frequent in patients with nephropathies and associated with progressive kidney disease and risk for end stage kidney disease. However, the relevance of deceased donor proteinuria on transplant outcome remains uncertain. In this nationwide cohort study, we evaluated the prevalence of proteinuria in deceased donor candidates and measured the impact on outcome after kidney transplantation. METHODS: Data from the Swiss Organ Allocation System and the Swiss Transplant Cohort Study were analyzed, comprising 1725 donors and 1516 recipients transplanted between 2008 and 2019. We correlated urine findings with donor characteristics and quantified the impact of proteinuria on allograft function at 12 months and survival. RESULTS: Proteinuria influenced allocation decisions in 4.5% of nonimmunological organ declines and was the leading cause for decline in 0.2% of cases. 74.1%, 51.4%, and 35.3% of donor candidates had a baseline proteinuria above 15, 30, and 50 mg protein/mmol urine creatinine, respectively. Proteinuria above 30 mg/mmol was associated with female donor sex, mechanical resuscitation, acute kidney injury, and time delay between ICU entry and urine sampling. Donor proteinuria was not associated with patient or allograft survival, nor allograft function at 12 months. CONCLUSION: We report a high prevalence of proteinuria in donor candidates, without evidence of a deleterious impact of proteinuria on graft function and/or survival. Therefore, low-level proteinuria should not be considered a limiting contraindication for kidney allocation in deceased donor transplant.

Sequential liver and kidney living donors: Making the ultimate gift twice.

There are nearly 150 living donors in the United States who donated more than one solid organ. Using our divisional database, we found 20 individuals who donated a liver and a kidney at different times. We performed a retrospective chart review of these donors, studying their motivating factors, complications and outcomes. The donors included 11 (55%) males and nine females. Thirteen (65%) donated the kidney before the liver. Fourteen (70%) were nondirected donors at the first donation, and four of the six directed donors in the first donation became nondirected in the second donation. Seventeen (85%) were nondirected at the second donation. Common reasons for donating the second time were a good experience with the first donation and knowing that one can donate again. Outcomes and the incidence of early complications were not significantly different after the 2nd versus the 1st donation. All donors recovered and currently are doing well. Our results show a significant number of dual organ donors are nondirected and motivated by their strong desire to help. A positive experience with the 1st donation often was the driving factor for the 2nd. A history of previous organ donation did not negatively impact the 2nd donation.

Recommendations for Evaluation and Selection of Deceased Organ Donor: Position Statement of ISCCM.

There is a wide gap between patients who need transplants and the organs that are available in India. Extending the standard donation criterion is certainly important to address the scarcity of organs for transplantation. Intensivists play a major role in the success of deceased donor organ transplants. Recommendations for deceased donor organ evaluation are not discussed in most intensive care guidelines. The purpose of this position statement is to establish current evidence-based recommendations for multiprofessional critical care staff in the evaluation, assessment, and selection of potential organ donors. These recommendations will give "real-world" criteria that are acceptable in the Indian context. The aim of this set of recommendations is to both increase the number and enhance the quality of transplantable organs. How to cite this article: Zirpe KG, Tiwari AM, Pandit RA, Govil D, Mishra RC, Samavedam S, et al. Recommendations for Evaluation and Selection of Deceased Organ Donor: Position Statement of ISCCM. Indian J Crit Care Med 2022;26(S2):S43-S50.

Testing deceased organ donors for infections: An organ procurement organization survey.

Organ procurement organizations (OPO) test potential deceased organ donors for infectious diseases required by policy, but many also perform testing for additional infections. The current state of donor testing in the United States is unknown. We sent an IRB approved survey to all 57 U.S. OPOs using REDCap. Descriptive statistics were performed. From the 57 OPOs, we received 46 (80.7%) unique responses with all 11 United Network of Organ Sharing regions represented. Forty of 46 (87%) OPO respondents consulted an Infectious Diseases physician when needed. Eighteen of 46 (39%) tested for West Nile virus (WNV) and 17 of 18 (94%) tested year-round. Eleven of 46 (23.9%) tested for Strongyloides infection while 17 of 46 (37%) tested for Chagas disease. All OPOs performed prospective nucleic acid testing (NAT) for HIV, hepatitis B and hepatitis C on all donors. OPO testing of additional infections has increased since prior surveys but remains variable. Standardization of organ donor infectious diseases evaluation should be considered.

Lung donation after medical assistance in dying at home.

Organ donation after medical assistance in dying (MAID) has only been possible for patients having the MAID procedure performed at a hospital facility due to prohibitive warm ischemic times. Herein, we describe a protocol for lung donation following MAID at home and demonstrate excellent postoperative outcomes. Lung donation following MAID at home is possible and should be considered by transplant programs.