Organ Recipients Research Articles

Family planning after transplantation: sex- and organ-related differences in the perception of medical counseling and social challenges

Abstract Purpose Transplant patients are increasingly of childbearing age. Organ-related health as well as pregnancy-related risks require a standardized approach to family planning counseling. The aim of this study was to explore sex- and organ-related counseling differences and expectations in family planning to improve counseling services and reduce risks after transplantation. Methods The study was designed as a cross-sectional, multi-center cohort study. A total of 251 participants aged between 18 and 45 years with a visceral or thoracic transplant completed a questionnaire on their attitude toward family planning and experience with medical consultation. Results More female than male participants had a desire to have children. Males believed their transplantation-related medication had an influence on their fertility, while women worried it could harm their child. Contraceptive counseling was negated by 43.6% of the women and 73.4% of the men. Medical advice regarding family planning was highly requested by both sexes. Women felt more influenced in their family planning than men. Female thoracic organ recipients worried about a pregnancy more than visceral organ recipients. Women showed great awareness for pregnancy-related risks with the majority wanting to plan a pregnancy beforehand. Conclusion The findings revealed a lack of contraceptive counseling and a lack of family planning advice by physicians.

A new heart transplant resource: DBD donor with out-of-hospital cardiac arrest

Abstract The aim of the present study is to analyze the differences in terms of cardiac transplant survival in organ recipients from a DBD (donor with brain death) donor characterized by out-of-hospital cardiac arrest (OHCA) and from a DBD donor not characterized by OHCA, in order to find new strategies to expand the donor pool. We analyzed the differences in mortality 30 days and 120 days after transplantation between the two groups of recipients, the length of stay in the ICU, the length of post-operative stay in the hospital, mechanical ventilation, the use of ECMO, the use of CVVH and the possible occurrence of ischemic and/or haemorrhagic stroke. 78 patients were compared: 13 recipients from a donor with OHCA with an average age of 55.18 (44.35 - 63.1) and 65 recipients from a donor without OHCA with an average age of 57.74 (50.9 - 66). The populations under study presented almost the same characteristics in terms of initial diagnosis, risk factors, comorbidities and list status. Comparing the results, no statistically significant differences were found between the two groups for ICU stay (p=1.000), for in-hospital stay (p=0.920) and for mechanical ventilation (p=0.95 ). No statistically significant difference was detected between the two groups even in terms of ECMO support (p=0.90), ischemic stroke (p=0.70), hemorrhagic stroke (p=0.781). From the analysis of the survival curves it can be seen that there is no statistically significant difference between the two groups either with regard to 30-day mortality (p=0.905) or 120-day mortality (p=0.957). The use of a DBD donor with OHCA represents a valid resource in the field of heart transplantation. In the present study it does not affect the recipient's survival rate. 30 days after heart transplantation mortality is conditioned by the intrinsic characteristics of the recipients.Kaplan-Meier 30 day survivalKaplan-Meier 30 day survival

Prevalence of hypertension and uncontrolled hypertension after solid organ transplantation: a 5-year follow-up of the Swiss Transplant Cohort Study.

Hypertension (HTN) increases cardiovascular risk and is a frequent finding across all solid organ transplant recipients. We describe the prevalence of HTN and uncontrolled HTN, as well as details on pharmacologic treatment of HTN across solid organs transplant recipients up to five years after transplantation. This retrospective study is nested in the prospective Swiss Transplant Cohort Study (www.stcs.ch) that includes kidney, heart, lung, and liver transplantation. Data extraction from 2008 to 2019 was used for this study and follow-up data at 6, 12 and 60 months was analyzed. A total of 3865 transplant recipients were included for analysis. The prevalence of HTN at 6 and 60 months was 88.9% and 90.4% in kidney (P = 0.21), 61.8% and 76.1% in liver (P < 0.01), 72.6% and 84.9% in lung (P < 0.01), and 89.3% and 85.8% in heart (P = 0.33) transplant recipients, respectively. The prevalence of uncontrolled HTN at 6 and 60 months was 40.3% and 38.9% in kidney (P = 0.48), 21.2% and 30.5% in liver (P = 0.05), 26.0% and 36.8% in lung (P = 0.03) and 38.9% and 18.5% in heart (P < 0.01) transplant recipients, respectively. At 12 months, compared to heart transplant recipients, kidney [odds ratio (OR) = 1.6, 95% confidence interval (CI) 1.1-2.1], liver (OR = 1.7, 95% CI 1.1-2.6) and lung (OR = 2.6, 95% CI 1.6-4.0) transplant recipients had a higher likelihood of presenting with uncontrolled HTN. HTN prevalence after solid organ transplantation is high. Uncontrolled and untreated HTN remain a major issue post transplantation, particularly in organ recipients not necessarily suffering from cardiovascular diseases such as liver or lung transplant recipients.

Non-Standard Risk Donors and Risk of Donor-Derived Infections: From Evaluation to Therapeutic Management.

Expected and unexpected donor-derived infections are a rare complication of solid organ transplantation, but can result in significant morbidity and mortality. Over the last years, the growing gap existing between patients on the waiting list and available organs has favored the use of organs from donors with suspected or confirmed infections, thanks to the improvement of risk mitigation strategies against transmission of well recognized and emerging infections. Given the recent developments, the particular interest of this review is to summarize data on how to maximize utilization of HIV+ donors in HIV+ recipients, the use of HCV-viremic donors and HBV positive donors. This article also covers the implications for recipient of organs from donors with bacteremia and the challenge of multidrug resistant (MDR) infections. Lastly this review describes emerging risks associated with recent Coronavirus Disease-2019 (COVID-19) pandemics.

Normothermic Regional Perfusion Experience of Organ Procurement Organizations in the US

Despite the unmet need for donor organs, organ use from donation after circulatory determination of death (DCD) donors has been limited by inferior transplant outcomes. Normothermic regional perfusion (NRP) improves recipient outcomes and organ utilization from DCD donors. There is variability in NRP policies and experience among US organ procurement organizations (OPOs). To determine OPO experience, identify operational inconsistencies, and explore needs related to NRP. This survey study included 55 OPOs in the US that had recovered DCD organs and completed a survey on operational, administrative, and educational components related to NRP in November to December 2023. Data analysis was performed from February to April 2024. The primary outcome was the number of OPOs participating in and/or anticipating NRP participation. Secondary outcomes were NRP implementation barriers, OPO education practices, and future needs regarding consensus NRP recommendations and standards. Of 55 respondents, 11 (20%) were chief executive officers, 8 (15%) were chief operating officers, and 36 (65%) were medical directors or chief clinical officers. Forty-nine OPOs facilitated NRP cases: 26 OPOs (53%) facilitated both thoracoabdominal NRP (TA-NRP) and abdominal NRP (A-NRP) cases, 16 OPOs (33%) facilitated only TA-NRP, and 7 OPOs (14%) facilitated only A-NRP. OPOs reported 606 NRP cases (421 TA-NRP [69%], 185 A-NRP [31%]); median (range) case experience was 8 (1-52). Fifty-two of 55 OPOs (95%) thought standardized guidance documents would be helpful. All 49 OPOs facilitated NRP at a transplant center's request; 39 (80%) had NRP initiated by a nonlocal transplant center. Twenty-three of 49 OPOs (47%) participated in NRP without a policy and without a policy pending approval. Positive donor hospital feedback was received by 29 OPOs (59%), primarily focused on increased organs transplanted and prerecovery communication. Allocation challenges were experienced by 21 OPOs (43%); their median (range) case volume was higher than those with no reported allocation challenges (11 [3-52] vs 6.5 [1-29]; P = .03). Eleven OPOs (22%) had incorporated NRP into general donor hospital education. In this survey study of US OPOs, wide variation existed with respect to NRP experience and practice. Allocation challenges occurred more frequently with increased NRP experience. NRP guidelines and standardization were desired by most OPOs to decrease allocation challenges and maximize the gift of organ donation.

Pig-to-human kidney xenotransplants using genetically modified minipigs

This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, β4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both Tcell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success.

Longitudinal analysis of viral dynamics in HIV+-to-HIV+ HOPE Act kidney-transplant recipients.

BACKGROUNDThe HIV Organ Policy Equity (HOPE) Act allows individuals living with HIV to accept organs from donors with HIV. This practice widens the pool of available organs, but also presents important virological issues, including the potential for HIV superinfection of the recipient, viral persistence in the kidney, and loss of virological control.METHODSWe addressed these issues by performing in-depth longitudinal viral sequence analyses on urine, blood, and urine-derived renal epithelial cells from 12 recipients of HIV+ kidney allografts.RESULTSWe amplified donor-derived HIV-1 env sequences in 5 out of 12 recipients after transplant. These donor-derived env sequences were amplified from recipient urine, urine-derived renal epithelial cells, and plasma between 12 and 96 hours after transplant and remained detectable up to 16 days after transplant. Env sequences were also detected in kidney biopsies taken from the allografts before implantation in 6 out of the 12 transplant cases, indicating the presence of donor virus within the organ. One recipient had a viremic episode 3.5 years after transplantation as a result of antiretroviral therapy (ART) interruption. Only recipient strain viral sequences were detected in blood, suggesting that the donor virus, if still present, was not reactivated during the temporary ART withdrawal.CONCLUSIONSThis study demonstrates that the HIV env sequences in a donor kidney can be amplified from biopsies taken from the allograft before implantation and can be detected transiently in blood and urine samples collected from the organ recipients after transplantation.FUNDINGNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant number R01DK131497.

Temporal trends in organ donation among cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation

AimsThis study explores the evolution of organ donation from patients treated with extracorporeal-cardiopulmonary-resuscitation (ECPR) for refractory out-of-hospital-cardiac-arrest (OHCA) and evaluates the public health benefits of a mature ECPR program. MethodsThis retrospective, single-center study included OHCA patients (2016–2023) who had mostly initial shockable rhythms and were treated with ECPR. Organ donation rates from non-survivors through these years were analyzed. The public health benefit of ECPR was determined by the ratio of the sum of survivors with Cerebral Performance Category 1–2 and non-survivors who donated at least 1 solid organ, to the total ECPR patients. Temporal trends were analyzed yearly using linear regression. ResultsOut of 419 ECPR patients presenting with refractory OHCA over the study period, 116 survived neurologically intact (27.7%). Among non-survivors (n = 303), families of 41 (13.5%) consented to organ donation (median age 51 years, 75.6% male) and organs from 38 patients were harvested, leading to 74 organ transplants to 73 recipients. The transplanted organs included 43 kidneys (58.1%), 27 livers (36.5%), 3 lungs (4%), and 1 heart (1.4%), averaging 2.4 ± 0.9 accepted organs/donor. The number of organ donors and successful transplants correlated positively with the years since the ECPR program’s initiation (ptrend = 0.009, ptrend = 0.01). Overall, 189 patients (116 survivors, 73 organ recipients) benefited from ECPR, achieving organ-failure-free survival. The cumulative public health benefit of ECPR, considering the 116 survivors and 38 donors was 36.8%. ConclusionThe public health benefits of an established ECPR program extend beyond individual ECPR patient survival, forming a new, previously under-recognized source of transplant donors.

Donor-derived infections-Insights from Singapore, Japan, and Thailand.

Solid organ transplantation (SOT) has expanded significantly in Asia over past few decades. Donor-derived infections (DDIs) remain a significant concern as they may adversely impact transplant outcomes. We aim to review the existing regulatory frameworks, screening protocols, and management practices for DDIs in Asia. We reached out to transplant infectious diseases experts in Asia to provide standardized data on annual SOT numbers, incidence of DDIs, regulatory frameworks, donor and recipient screening protocols, and DDI surveillance measures. We present the data from Singapore, Japan, and Thailand. Donor screening for HIV, hepatitis B, hepatitis C, and syphilis is mandatory in all countries. Additionally, Japan screens for HTLV-1 antibody due to its endemicity. We also reviewed the protocols for screening and prevention of endemic infections in Asia. Singapore is the only country implementing universal screening for all donors for dengue, Zika, and chikungunya via blood and urine RT-PCR. Strongyloidiasis screening is not routinely done, although some transplant centers empirically give ivermectin prophylaxis to organ recipients. Tuberculosis screening with a donor questionnaire and chest radiograph is common for deceased donors, and some centers do Interferon Gamma Release Assay test for living donors. We also found a significant gap in the surveillance and reporting of potential DDIs in Asia and the overall incidence of DDIs in Asia is unknown and likely underreported. The experiences of Singapore, Japan, and Thailand offer valuable insights into current practices and the unmet needs regarding a DDI registry and call for coordinated efforts to address this critical issue in the region.

SIGNET: protocol for a multicentre, single-blind prospective, group sequential, randomised controlled trial to evaluate the benefits of a single dose of simvastatin given to potential organ donors declared dead by neurological criteria on outcomes in organ recipients

IntroductionSuccessful organ transplantation in patients with end-stage organ failure improves long-term survival, improves quality of life and reduces costs to the NHS. Despite an increase in the number of deceased...

Identification of HIV infection in two solid organ recipients three years after transplantation

Routine screening of organ donors to detect human immunodeficiency virus (HIV) infection has detected the rare transmission of the virus through organ transplantation. However, despite routine screening, HIV transmission remains a risk in organ transplantation since, unlike tissues, solid organs cannot be processed, disinfected, or modified to inactivate infectious pathogens. A case of possible transmission of HIV by organ transplant is described below, from a previously seronegative donor to two recipients.

Providing red blood cells to facilitate organ transplant via normothermic perfusion techniques: A single-center experience.

Normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) are organ procurement and transport techniques that can improve organ quality, facilitate longer transport, and reduce postoperative complications, increasing organ availability and improving outcomes. NRP and NMP often require allogeneic red blood cells (RBCs). Our academic transfusion service began providing RBCs to support NRP and NMP for adult heart transplant (HT), orthotopic liver transplant (OLT), and multiorgan transplant (MOT) in August 2020. This single-center, retrospective study describes the implementation process and analyzes the characteristics of RBC support during the first 3 years of the perfusion programs. Timing and quantity of units issued and used, organ recipient demographics, and transplant outcomes were obtained from transfusion service and electronic medical records. From 2020 to 2023, the transfusion service received 233 requests to support NRP and NMP perfusion cases. Of these, 105 cases resulted in RBC use, and units were returned or discarded in 112 cases. A total of 131 patients received perfusion-facilitated transplants (92 HT, 27 OLT, and 12 MOT). The majority of perfusion-facilitated HTs utilized NRP (81/92, 88%), whereas most perfusion-facilitated OLTs utilized NMP (21/27, 78%). Across all 233 requests, a total of 381 RBC units were used to facilitate 131 transplants, averaging 2.91 units/transplant. Provision of RBCs for NRP and NMP techniques represents a novel method for transfusion services to support and facilitate life-saving organ transplants with only modest product use, about three RBC units per organ transplant in this single-center study.

Allocation Rules and Age-Dependent Waiting Times for Kidney Transplantation.

Rigid age limits in the current allocation system for post-mortem donor kidneys in Germany may have problematic effects. The new German national transplantion registry enables data analysis with respect to this question. Using anonymized data from the German national transplantion registry, we extracted and evaluated information on the recipients and postmortem donors of kidneys that were allocated in Germany through Eurotransplant over the period 2006-2020. Data on 19 664 kidney transplantations in Germany from 2006 to 2020 were analyzed. The median waiting time for kidney transplantation was 5.8 years. Persons under age 18 waited a median of 1.7 years; persons aged 18 to 64, 7.0 years; and persons aged 65 and older, 3.8 years. Over the period of observation, postmortem kidneys were transplanted into 401 people of age 64 (2.0% of all organ recipients) and 1,393 people of age 65 (7.1% of all organ recipients). The difference in waiting times between allocation programs for persons under age 65 (ETKAS, "Eurotransplant Kidney Allocation System") and those aged 65 and older (ESP, "Eurotransplant Senior Program") increased over the period of observation, from 2.6 years in 2006-2010 to 4.1 years in 2017-2020. The rigid age limits in the current allocation rules for post-mortem kidney donations in Germany are prolonging the waiting times for transplants among patients aged 18 to 64. We think these rules need to be fundamentally reassessed.

Kidney transplantation and gut microbiota.

Kidney transplantation is an effective way to improve the condition of patients with end-stage renal disease. However, maintaining long-term graft function and improving patient survival remain a key challenge after kidney transplantation. Dysbiosis of intestinal flora has been reported to be associated with complications in renal transplant recipients. The commensal microbiota plays an important role in the immunomodulation of the transplant recipient responses. However, several processes, such as the use of perioperative antibiotics and high-dose immunosuppressants in renal transplant recipients, can lead to gut dysbiosis and disrupt the interaction between the microbiota and the host immune responses, which in turn can lead to complications such as infection and rejection in organ recipients. In this review, we summarize and discuss the changes in intestinal flora and their influencing factors in patients after renal transplantation as well as the evidence related to the impact of intestinal dysbiosis on the prognosis of renal transplantation from in vivo and clinical studies, and conclude with a discussion of the use of microbial therapy in the transplant population. Hopefully, a deeper understanding of the function and composition of the microbiota in patients after renal transplantation may assist in the development of clinical strategies to restore a normal microbiota and facilitate the clinical management of grafts in the future.

Unique Lessons From the Natural Progression of Rejection in Human Uterine Allografts.

Uterus transplantation (UTx) is a novel treatment for absolute uterine infertility. Acute T cell-mediated rejection (TCMR) can be monitored only through serial cervical biopsies. This study, the first of its kind in human transplantation, evaluated clinical, serological, and pathophysiological manifestations of allograft rejection from immunosuppression withdrawal (ISW) to graft hysterectomy (Hx). Following live birth, immunosuppression was abruptly withdrawn from six living-donor UTx recipients. ISW occurred at a median of 7.4 weeks before graft Hx. Post-ISW signs of rejection included: (1) discoloration of the cervix; (2) increased uterine size compared to day of ISW; (3) serological evidence of eosinophilia and progressive development of donor-specific antibodies (DSA) or child-specific antibodies (CSA); (4) histopathological evidence of TCMR in cervical biopsies preceding the development of antibodies in serum; and (5) C4d deposition in tissue before formation of DSA or CSA in all but two recipients. At graft Hx, endometrial glands were preferentially targeted for destruction over stroma while parametrial arteries displayed variable arteritis and fibrointimal hyperplasia. Recognition of the progression of uterine allograft rejection may be important for other human organ recipients and drive research on modulation of immunosuppression and the paradoxical relationship between adaptive cellular and humoral immunity in natural pregnancies. ClinicalTrials.gov identifier: NCT02656550.

Impact of machine perfusion on transplant infectious diseases: New challenges and opportunities.

Preservation techniques that maintain the viability of an organ graft between retrieval from the donor and implantation into the recipient remain a critical aspect of solid organ transplantation. While traditionally preservation is accomplished with static cold storage, advances in ex vivo dynamic machine perfusion, both hypothermic and normothermic, have allowed for prolongation of organ viability and recovery of marginal organs effectively increasing the usable donor pool. However, the use of these novel machine perfusion technologies likely exposes the recipient to additional infectious risk either through clonal expansion of pathogens derived during organ recovery or de novo exogenous acquisition of pathogens while the organ remains on the machine perfusion circuit. There is a paucity of high-quality studies that have attempted to quantify infection risk, although it appears that prolonging the time on the machine perfusion circuit and normothermic parameters increases the risk of infection. Conversely, the use of ex vivo machine perfusion unlocks new opportunities to detect and treat donor-derived infections before implantation into the recipient. This review seeks to reveal how the use of ex vivo machine perfusion strategies may augment the risk of infection in the organ recipient as well as outline ways that this technology could be leveraged to enhance our ability to manage donor-derived infections.

Revolutionizing Organ Transplantation with Robotic Surgery.

To evaluate the impact of robotic techniques on organ transplantation outcomes. The evolution of organ transplantation is becoming influenced by the adoption of minimally invasive techniques, transitioning from laparoscopic to robotic methods. Robotic surgery has emerged as a significant advancement, providing superior precision and outcomes compared to traditional approaches. This perspective includes a systematic review of the literature, original data from a high-volume center, as well as an international survey focusing on perceptions related to robotic versus laparoscopic and open approaches. The systematic review and meta-analysis revealed lower morbidity with robotic donor nephrectomy, recipient kidney transplant and donor hepatectomy. Our center's experience, with over 3,000 minimally invasive transplant procedures (kidney, liver, donor, and recipient), supports the superiority of Robotic Transplant Surgery (RTS). The global survey confirms this shift, revealing a preference for robotic approaches due to their reduced morbidity, despite challenges such as access to the robotic system and cost. This comprehensive overview including a systematic review, original data, and perceptions derived from the international survey demonstrate the superiority of Robotic Transplant Surgery (RTS) across a range of organ transplantations, for both donors and recipients. The future of RTS depends on the efforts of the surgical community in addressing challenges such as economic implications, the need for specialized surgical training for numerous surgeons, as well as wide access to robotic systems worldwide.

Minimizing risk while maximizing opportunity: The infectious disease organ offer process survey.

The purpose of this study was to understand how transplant infectious disease (TID) physicians assess a potential donor with known or suspected infection and describe posttransplant management. We designed a survey of 10 organ offer scenarios and asked questions pertaining to organ acceptability for transplantation and management posttransplant. The survey was distributed to TID clinicians via transplant society listservs and email. Responses were recorded in REDCap, and descriptive statistics were employed. One hundred thirteen infectious disease physicians responded to the survey, of whom 85 completed all cases. Respondents were generally in agreement regarding organ acceptability, although some divergence was seen when evaluating lungs from donors with influenza, tuberculosis, or multidrug-resistant Acinetobacter infection. Posttransplant management showed more variation. Areas of optimization were identified: (1) Further understanding of where risk-mitigation strategies within the donor offer process may improve donor acceptability and therefore organ utilization; (2) importance of recipient considerations in assessing degree of infectious risk; and (3) gaps in evidenced-based data regarding optimal posttransplant management of recipients. Evaluation of donor offers by TID clinicians is a complex process. Although the survey does not itself serve to make recommendations regarding best practices, it highlights areas where generation of data to inform acceptance and management practices may allow for improved organ utilization and recipient management.

Outcomes in solid organ transplant recipients receiving organs from a donor with Fusarium solani species complex meningitis.

Five organs (heart, right lung, liver, right, and left kidneys) from a deceased patient were transplanted into five recipients in four US states; the deceased patient was identified as part of a healthcare-associated fungal meningitis outbreak among patients who underwent epidural anesthesia in Matamoros, Mexico. After transplant surgeries occurred, Fusarium solani species complex, a fungal pathogen with a high case-mortality rate, was identified in cerebrospinal fluid from the organ donor by metagenomic next-generation sequencing (mNGS) and fungal-specific polymerase chain reaction and in plasma by mNGS. Four of five transplant recipients received recommended voriconazole prophylaxis; four were monitored weekly by serum (1-3)-β-d-glucan testing. All five were monitored for signs of infection for at least 3 months following transplantation. The liver recipient had graft failure, which was attributed to an etiology unrelated to fungal infection. No fungal DNA was identified in sections of the explanted liver, suggesting that F. solani species complex did not contribute to graft failure. The remaining recipients experienced no signs or symptoms suggestive of fusariosis. Antifungal prophylaxis may be useful in preventing donor-derived infections in recipients of organs from donors that are found to have Fusarium meningitis.

Clinical approach to donor-derived infection in solid organ transplant recipients.

Donor-derived infection is an uncommon but potentially devastating complication of solid organ transplantation (SOT). Accurate and timely identification of unexpected infectious disease transmission events has implications not only for the recipient(s) experiencing infection, but also other recipients of organs or tissues from the same donor who may require additional testing or risk mitigation, as well as the broader organ transplant regulatory framework. This narrative review synthesizes data from published reports of symptomatic unexpected donor-derived infections in SOT recipients to provide clinicians with a systematic approach to the evaluation of undifferentiated illnesses that may be of donor origin. Key reasons to consider donor-derived infection include certain microbiologically proven infections in the recipient, especially early after transplant, characteristics of the donor or their management that suggest potential exposure to or infection with specific pathogens prior to organ procurement, and select clinical syndromes that occur in the post-transplant period. Syndromes for which expedited consideration and evaluation of donor-derived infection may be warranted include central nervous system infection, graft or perigraft complications developing in the absence of typical risk factors, and unexplained critical illness/sepsis syndrome in the early post-transplant period. When embarking on an investigation of a suspected donor-derived infection, clinicians should apply knowledge of the entire continuum of the organ procurement and transplant process to ensure unbiased and comprehensive data collection that will facilitate appropriate adjudication of these uncommon but high-consequence events.