Nonstandard Donors Research Articles

Neonatal heart transplantation in the United States: Trends and outcomes.

Heart transplantation in the neonatal period is associated with excellent survival. However, outcomes data are scant and have been obtained primarily from two single-center reports within the United States. We sought to analyze the outcomes of all neonatal heart transplants performed in the United States using the United Network for Organ Sharing (UNOS) dataset. The UNOS dataset was queried for patients who underwent infant heart transplantation from 1987 to 2021. Patients were divided into two groups based on age - neonates (<=31 days), and older infants (32 days-365 days). Demographic and clinical characteristics were analyzed and compared, along with follow up survival data. Overall, 474 newborns have undergone heart transplantation in the United States since 1987. Freedom from death or re-transplantation for neonates was 63.5%, 58.8% and 51.6% at 5, 10, and 20 years, respectively. Patients in the newborn group had lower unadjusted survival compared to older infants (p < .001), but conditional 1-year survival was higher in neonates (p = .03). On multivariable analysis, there was no significant difference in survival between the two age groups (p = .43). Black race, congenital heart disease diagnosis, earlier surgical era, and preoperative mechanical circulatory support use were associated with lower survival among infant transplants (p < .05). Neonatal heart transplantation is associated with favorable long-term clinical outcomes. Neonates do not have a significant survival advantage over older infants. Widespread applicability is limited by the small number of available donors. Efforts to expand the donor pool to include non-standard donor populations ought to be considered.

Advancing our standards: Do we need to standardize the use of nonstandard donor organs in patients with low MELD?

Advancing our standards: Do we need to standardize the use of nonstandard donor organs in patients with low MELD?

Transplant center variability in utilizing nonstandard donors and its impact on the transplantation of patients with lower MELD scores.

There is a subset of patients with lower MELD scores who are at substantial risk of waitlist mortality. In order to transplant such patients, transplant centers must utilize "nonstandard" donors (eg, living donors, donation after circulatory death), which are traditionally offered to those patients who are not at the top of the waitlist. We used Organ Procurement and Transplantation data to evaluate center-level and region-level variability in the utilization of nonstandard donors and its impact on MELD at transplant among adult liver-alone non-status 1 patients transplanted from April 1, 2020, to September 30, 2022. The center-level variability in the utilization of nonstandard donors was 4-fold greater than the center-level variability in waitlisting practices (waitlistings with a MELD score of <20). While there was a moderate correlation between center-level waitlisting and transplantation of patients with a MELD score of <20 ( p = 0.58), there was a strong correlation between center-level utilization of nonstandard donors and center-level transplantation of patients with a MELD score of <20 ( p = 0.75). This strong correlation between center-level utilization of "nonstandard" donors and center-level transplantation of patients with a MELD score of <20 was limited to regions 2, 4, 5, 9, and 11. Transplant centers that utilize more nonstandard donors are more likely to successfully transplant patients at lower MELD scores. Public reporting of these data could benefit patients, caregivers, and referring providers, and be used to help maximize organ utilization.

The Effect of Ideal/Standard Donor and Marginal Donor Use on Primary Graft Dysfunction After Lung Transplantation in Turkey.

The transplantation waiting list is getting longer day by day with the spread of lung transplantation and awareness of it. However, the donor pool cannot keep up with this rate. Therefore, nonstandard (marginal) donors are widely used. By studying the lung donors presented at our center, we aimed to raise awareness of the donor shortage and compare clinical outcomes in recipients with standard and marginal donors. The data from recipients and donors of lung transplants performed at our center between March 2013 and November 2022 were retrospectively reviewed and recorded. Transplants with ideal and standard donors were classified as group 1, and those with marginal donors were classified as group 2. Primary graft dysfunction rates, intensive care unit, and hospital stay days were compared. Eighty-nine lung transplants were performed. A total of 46 recipients were in group 1 and 43 were in group 2. There were no differences between groups in the development of stage 3 primary graft dysfunction. However, a significant difference was found in the marginal group for developing any stage primary graft dysfunction. Donors were mostly from the western and southern regions of the country and from the education and research hospitals. Because of the donor shortage in lung transplantation, transplant teams tend to use marginal donors. Stimulating and supportive education for healthcare professionals to recognize brain death and public education to raise awareness about organ donation are necessary to spread organ donation throughout the country. Although our results using marginal donors are similar with the standard group, each recipient and donor should be assessed individually.

Outcomes of Nonstandard Donor Kidney Transplants in Recipients Aged 70 Years or More: A Single-Center Experience.

There is a global increase in the prevalence of end-stage kidney disease among the elderly. As a result, more elderly recipients are being considered for kidney transplants. Because of the scarcity of donor organs, such patients are more likely to receive transplants from nonstandard donor kidneys.Here, we examined the outcomes of kidney transplants with a nonstandard donor allograftin recipients ≥70 years of age. Records of patients who received transplants at a single UK centerfrom April 1, 2015, through March 31, 2021, were retrospectively analyzed to identify those who were ≥70 years old at the time of surgery. Outcomes ofthose who received a kidney transplantfrom a nonstandard donor (group 1) were compared to those who received a kidney transplant from a standard criteria donor or living donor (group 2). During the study period, of 670 kidney transplant procedures, 67 recipients (10%) were ≥70 years of age at the time of surgery, with 54 (80.6%) identified in group 1 and 13 (19.4%) identified in group 2. Cold ischemia time (P = .001) and incidence of delayed graft function (P = .044) were significantly higherin group 1. Duration of graft survival atthe end of follow-up was not different between the groups (log rank = 0.218), butthe mean serum creatinine values at 2 years (P = .016) and 3 years (P = .048) years were significantly higherin group 1. Patients in group 1 had shorter survival time (log rank = 0.037). Nonstandard donor kidneys should be used cautiously in elderly recipients as patient survival was shown to be comparatively poor compared with elderly recipients who received a kidney transplant from a standard criteria donor or a living donor.

Reactive Oxygen Species Induce Fatty Liver and Ischemia-Reperfusion Injury by Promoting Inflammation and Cell Death.

Liver transplantation is the ultimate method for treating end-stage liver disease. With the increasing prevalence of obesity, the number of patients with non-alcoholic fatty liver, a common cause of chronic liver disease, is on the rise and may become the main cause of liver transplantation in the future. With the increasing gap between the number of donor livers and patients waiting for liver transplantation and the increasing prevalence of non-alcoholic fatty liver, the proportion of steatosis livers among non-standard donor organs is also increasing. Ischemia-reperfusion injury has historically been the focus of attention in the liver transplantation process, and severe ischemia-reperfusion injury leads to adverse outcomes of liver transplantation. Studies have shown that the production of reactive oxygen species and subsequent oxidative stress play a key role in the pathogenesis of hepatic ischemia and reperfusion injury and non-alcoholic fatty liver. Furthermore, the sensitivity of fatty liver transplantation to ischemia-reperfusion injury has been suggested to be related to the production of reactive oxygen species (ROS) and oxidative stress. In ischemia-reperfusion injury, Kupffer cell and macrophage activation along with mitochondrial damage and the xanthine/xanthine oxidase system promote marked reactive oxygen species production and the inflammatory response and apoptosis, resulting in liver tissue injury. The increased levels of ROS and lipid peroxidation products, vicious circle of ROS and oxidative stress along with mitochondrial dysfunction promoted the progress of non-alcoholic fatty liver. In contrast to the non-fatty liver, a non-alcoholic fatty liver produces more reactive oxygen species and suffers more serious oxidative stress when subjected to ischemia-reperfusion injury. We herein review the effects of reactive oxygen species on ischemia-reperfusion injury and non-alcoholic fatty liver injury as well as highlight several treatment approaches.

Heart Transplantation in Systemic Diseases: How Far Can We Go?

Purpose Few data are already available on the follow up of heart transplant (HTx) patients for systemic rare diseases. Aim of the study was to assess the cardiovascular, non-cardiovascular outcome and quality of life (QoL) of heart transplant patients with systemic diseases. Methods We have reviewed all the cases of HTx in rare diseases performed in our Cardiothoracic Department from 1985 to Feb 2021. QoL was assessed by SF-36 questionnaire. Results Since 1985, out of the 680 HTx performed at our Centre, 25 patients had a systemic rare disease (cardiac amyloidosis, Danon, Becker distrophy, see Fig 1) as cause of advanced heart failure (HF) needing of HTx. Mean age was 45±15 years old, mostly males (76%); 3 patients were in urgent list. The peripheral muscular involvement was present in 11 cases; however, almost all patients retained the capacity of walking. Donors mean age was 37±11 and 16 (64%) were male. Eleven (44%) were considered non-standard donors (ischemic time >4 hours in 5 (20%), cardiac arrest or LVEF<50% or coronary artery disease in 3 (12%), previous drug abuse in 2 (8%). Considering the cardiovascular outcome, the survival was 100% at 30-days, 96% and 90% at 1 and 5 years after HTx in a median follow up of 72 (range 7-318) months. Rejection >2 grade was in 6 (24%), while cardiac allograft vasculopathy in 4 (16%). Related the non-cardiovascular outcome, there was ocular and muscular worsening in 6 (24%) and 9 (36%) cases, while 3 (12%) developed severe psychosis. Lastly, the SF-36 questionnaire showed lower scores for the items related to Physical Component Summary, while similar scores compared to the general population for the Mental Component Summary. Conclusion In a median follow up of 5 years, HTx patients with systemic rare disease showed a satisfied general survival. The ocular and muscular worsening related to the systemic disease could be very frequent, conditioning the QoL. The relapse of the systemic disease is a rare event, although possible. Few data are already available on the follow up of heart transplant (HTx) patients for systemic rare diseases. Aim of the study was to assess the cardiovascular, non-cardiovascular outcome and quality of life (QoL) of heart transplant patients with systemic diseases. We have reviewed all the cases of HTx in rare diseases performed in our Cardiothoracic Department from 1985 to Feb 2021. QoL was assessed by SF-36 questionnaire. Since 1985, out of the 680 HTx performed at our Centre, 25 patients had a systemic rare disease (cardiac amyloidosis, Danon, Becker distrophy, see Fig 1) as cause of advanced heart failure (HF) needing of HTx. Mean age was 45±15 years old, mostly males (76%); 3 patients were in urgent list. The peripheral muscular involvement was present in 11 cases; however, almost all patients retained the capacity of walking. Donors mean age was 37±11 and 16 (64%) were male. Eleven (44%) were considered non-standard donors (ischemic time >4 hours in 5 (20%), cardiac arrest or LVEF<50% or coronary artery disease in 3 (12%), previous drug abuse in 2 (8%). Considering the cardiovascular outcome, the survival was 100% at 30-days, 96% and 90% at 1 and 5 years after HTx in a median follow up of 72 (range 7-318) months. Rejection >2 grade was in 6 (24%), while cardiac allograft vasculopathy in 4 (16%). Related the non-cardiovascular outcome, there was ocular and muscular worsening in 6 (24%) and 9 (36%) cases, while 3 (12%) developed severe psychosis. Lastly, the SF-36 questionnaire showed lower scores for the items related to Physical Component Summary, while similar scores compared to the general population for the Mental Component Summary. In a median follow up of 5 years, HTx patients with systemic rare disease showed a satisfied general survival. The ocular and muscular worsening related to the systemic disease could be very frequent, conditioning the QoL. The relapse of the systemic disease is a rare event, although possible.

The organ procurement costs of expanding deceased donor organ acceptance criteria: Evidence from a cost function model

A potential solution to the deceased donor organ shortage is to expand donor acceptability criteria. The procurement cost implications of using nonstandard donors is unknown. Using 5years of US organ procurement organization (OPO) data, we built a cost function model to make cost projections: the total cost was the dependent variable; production outputs, including the number of donors and organs procured, were the independent variables. In the model, procuring one kidney or procuring both kidneys from double/en bloc transplantation from a single-organ donor resulted in a marginal cost of $55k (95% confidence interval [CI] $28k, $99k) per kidney, and procuring only the liver from a single-organ donor results in a marginal cost of $41k (95% CI $12k, $69k) per liver. Procuring two kidneys for two candidates from a donor lowered the marginal cost to $36k (95% CI $22k, $66k) per kidney, and procuring two kidneys and a liver lowers the marginal cost to $24k (95% CI $17 k, $45 k) per organ. Economies of scale were observed, where high OPO volume was correlated with lower costs. Despite higher cost per organ than for standard donors, kidney transplantation from nonstandard donors remained cost-effective based on contemporary US data.

Pathological features and outcomes of incidental renal cell carcinoma in candidate solid organ donors.

BackgroundWe report the findings of a single Italian center in the evaluation of renal lesions in deceased donors from 2001 to 2017. In risk evaluation, we applied the current Italian guidelines, which include donors with small (< 4 cm, stage pT1a) renal carcinomas in the category of non-standard donors with a negligible risk of cancer transmission.MethodsFrom the revision of our registries, 2,406 donors were considered in the Emilia Romagna region of Italy; organs were accepted from 1,321 individuals for a total of 3,406 organs.ResultsThe evaluation of donor safety required frozen section analysis for 51 donors, in which a renal suspicious lesion was detected by ultrasound. Thirty-two primary renal tumors were finally diagnosed 26 identified by frozen sections and 6 in discarded kidneys. The 32 tumors included 13 clear cell renal cell carcinomas (RCCs), 6 papillary RCCs, 6 angiomyolipomas, 5 oncocytomas, 1 chromophobe RCC, and 1 papillary adenoma. No cases of tumor transmission were recorded in follow-up of the recipients.ConclusionDonors with small RCCs can be accepted to increase the donor pool. Collaboration in a multidisciplinary setting is fundamental to accurately evaluate donor candidate risk assessment and to improve standardized protocols for surgeons and pathologists.

Non-standard Donor Organs in Pediatric Lung Transplantation Have No Negative Impact on Recipients Outcome

Non-standard Donor Organs in Pediatric Lung Transplantation Have No Negative Impact on Recipients Outcome

Nonstandard Donor Organs in Pediatric Lung Transplantation have no Negative Impact on Recipients Outcome

Nonstandard Donor Organs in Pediatric Lung Transplantation have no Negative Impact on Recipients Outcome

Cultural competency of a mobile, customized patient education tool for improving potential kidney transplant recipients' knowledge and decision-making.

Patients considering renal transplantation face an increasingly complex array of choices as a result of the revised kidney transplant allocation system. Decision aids have been shown to improve patient decision-making through the provision of detailed, relevant, individualized clinical data. A mobile iOS-based application (app) including animated patient education and individualized risk-adjusted outcomes following kidney transplants with varying donor characteristics and DSA waiting times was piloted in two large US transplant programs with a diverse group of renal transplant candidates (N=81). The majority (86%) of patients felt that the app improved their knowledge and was culturally appropriate for their race/ethnicity (67%-85%). Patients scored significantly higher on transplant knowledge testing (9.1/20 to 13.8/20, P<.001) after viewing the app, including patients with low health literacy (8.0 to 13.0, P<.001). Overall knowledge of and interest in living and deceased donor kidney transplantation increased. This pilot project confirmed the benefit and cultural acceptability of this educational tool, and further refinement will explore how to better communicate the risks and benefits of nonstandard donors.

Organ transplantation from marginal and non-standard risk donors: ethical requisites for consent from recipients.

In order to close the gap between available organs and patients needing transplants, the selection criteria for donors have gradually become more relaxed and many countries have defined expanded criteria for donor variables. However, the use of organs from marginal and non-standard risk donors poses considerable ethical issues. The acceptability of the risk/benefit ratio depends primarily on a clinical assessment, and information given to the recipient and his/her eventual consent are crucial. Some of the requisites concerning information and consent are mandatory. Once these requisites have been defined in binding regulations, adequate margins must be allowed for their personalisation and to account for the unique nature of each physician/patient relationship. Each decision should be specific for a particular person, and it must be accepted that similar clinical situations may give rise to differing solutions that are nonetheless agreed by the physician and the patient.

NON-STANDARD KIDNEYS FOR TRANSPLANTS: CLINICAL MARGINS, MEDICAL MORALITY, AND THE LAW

Advances in kidney transplantation over the past six decades have been impressive, but have not eliminated the significant variability in outcome related to donor organ quality. Organ shortage means that, in addition to 'standard' deceased donor kidneys (SD), 'non-standard donor' (NSD), 'expanded criteria donor', or 'marginal' kidneys, which fail to meet standard criteria and are often associated with less good outcomes, are now being transplanted into selected recipients as a means of increasing the donor pool. A similar, but less-documented, practice has developed in living donation. This article outlines the clinical rationale and ethical argument underpinning the use of such donor kidneys and examines their legal status in the UK, which we claim remains largely undefined and untested. While it is probable that the general principles governing medico-legal consent and liability also apply to organ donation, the special circumstances of donation, notably the inadequate supply of donors and the emphasis on a 'gift relationship', make it difficult to know how far existing medico-legal precedents can or should apply. The non-standard status of deceased donor organs creates potential problems for the validity of 'appropriate consent' to donation required by statute. It may also be relevant to the use of interventions intended to optimise deceased donor organ quality. Furthermore, the SD/NSD distinction in clinical practice may produce unexpected legal effects. For example, the recent UK Regulations 2012, which bring into force the EU Directive on standards of quality and safety of human organs intended for transplantation, could produce a negative legal restraint on the use of NSD kidneys. There is an urgent need for clarification of the effect of using NSDs in areas such as recipient and donor consent, liability for negligence, and the law of product liability. Some argue that the need for non-standard organs results from society's failure to compel the retrieval of all suitable standard organs from the deceased as a community resource. However, the Human Tissue Acts of 2004 and 2006 (Scotland), which govern organ donation and transplantation in the UK, expressly require individual consent or authorisation in the decision to donate. This emphasis on individual autonomy appears to chime with prevailing public opinion. However, the sense of medico-legal security gained by uncritical observance of the existing law and of directives published under its authority may be an obstacle to the development of a system which adequately meets the needs of recipients while safeguarding donor autonomy.

Immunosuppressive Therapy in Non-Standard Donor Kidney Recipients: Results of a Cohort Study with An Everolimus Based/Calcineurin Inhibitors Free Protocol

Immunosuppressive Therapy in Non-Standard Donor Kidney Recipients: Results of a Cohort Study with An Everolimus Based/Calcineurin Inhibitors Free Protocol

Biobank Concept in Poland

Possible adverse events and reactions associated with organ procurement and transplantation from deceased donors require compliance with quality and safety standards. Shortage of organs for transplantation makes it necessary to obtain organs from nonstandard (expanded-criteria) donors. This increases the risk of disease transmission with the graft which is difficult or impossible to identify before transplantation. The long-term access to biologic material of organ donors and recipients proffers the possibility to evaluate serious adverse reactions as well as to improve the quality and safety in transplantation medicine. Implementation of the above-mentioned tasks requires a Biobank whose aims are: to gather and long-term storage sera, lymph nodes, and other tissues of deceased organ donors for analysis of their biologic properties; to gather and store organ recipient sera; to determine methods to store biologic material in a manner enabling identification of the donor, organ, and recipients; and to provide electronic record keeping. Tactical tasks of a Biobank are: to carry out new or verify results of previously performed testing of deceased donors and recipients as controls to evaluate transmission of infection; to perform genetic material testing (NAT) to verify and confirm serologic tests, eg, determination of HIV RNA/DNA in donors at risk of infections; to discover rare diseases in donors and recipients whose detection before transplantation is difficult because of the time constraints related to organ storage or the lack of available methods (eg, sponge encephalopathies); to perform biochemical or genetic tests to evaluate neoplasia transfer from donor to recipient; and to reexamine HLA typing in cases of immunologic complications.

Risk Factors in Cadaveric Donors of Livers Procured for Elective and Urgent Recipients

Use of livers from cadaveric nonstandard donors has become justified, especially for recipients awaiting urgent transplantations. However, it is known that results are superior when organs are obtained from ideal rather than expanded-criteria donors. We designed a study to compare the characteristics of 582 liver donors whose organs were used for elective versus urgent transplantations in 2006–2008 and the recipients' outcomes. Donors and recipients were classified into 2 groups: 1) elective (n = 387); and 2) urgent transplantations (n = 195). We evaluated 12 donor risk factors: age >55 years, alcohol ingestion, intensive care unit stay >4 days, hypotensive episodes (<70 mm Hg >10 min), noradrenaline dose >0.1 μg/kg/min, anti–hepatitis B of core (+), Na level >155 mmol/L, international normalized ratio >1.5, aspartate transaminase >140 U/L, alanine transaminase >170 U/L, bilirubin >2.0 mg/dL, and changes in liver sonography. There were no significant differences in the frequency of incidence of 11 donor risk factors in both groups. Only sodium level >155 mEq/L significantly (P = .04) differed. Donors for elective recipients showed this factor more frequently than the urgent cohort. The mean number of risk factors per donor among the elective cases was 2.28 and for the urgent cases 2.3, a difference that was not significant. In almost all cases of liver transplantations (94%), donor-related risk factors were acceptable. The criteria for cadaveric liver donors were not different for elective versus urgent recipients; biologic characteristics of the transplanted organs were similar in both groups. A tendency was not observed to expand donor criteria for urgent recipients.

Donor-Recipient MELD-Based Match in a Patient Who Required Three Liver Grafts in the Era of Nonstandard Donors: Case Report

In recent studies, nonstandard donors and high Model for End-stage Liver Disease (MELD) values have been indicated as risk factors for both graft survival and patient survival. A recent debate concerns which donor and recipient match guarantees the best results in terms of early and late survival. To emphasize the role of the donor–recipient match, we have reported herein a complex case of a patient who changed his preoperative risk status, being transplanted three times using donors of different risk levels. At each transplant, the patient moved to a higher MELD class: first transplant MELD = 22; second transplant MELD = 37; third transplant MELD = 38. Only at the third transplant did the patient recover. Besides the liver, almost all his organs (kidneys, heart, lungs) recovered in a few weeks, as well. Unfortunately, severe cortical and subcortical brain damage remained a crucial limiting impairment, leading to death 5 months later, due to pulmonary infection, yet with a perfectly working liver. We underlined the role of donor factors to predict the outcome after liver transplantation in the MELD era.

Lung transplantation in older patients?

Age 65 years and older is generally considered a contraindication to lung transplantation. Our group has offered lung transplantation to select patients 65 years of age and older who lack other comorbid conditions. We sought to define the short- and medium-term outcome of lung transplantation in patients aged 65 years and older. We reviewed the records of our lung transplant recipients from March 2000 to September 2006. During this interval, 50 patients were 65 years or older at the time of transplantation. Fifty patients younger than 65 years were matched to the older cohort by means of propensity analysis. The demographics and perioperative and postoperative characteristics and survival of the 2 groups were compared. Older patients were more likely to receive single-lung transplantation (older group: 76% vs younger group: 16%, P < .05) and nonstandard donor lungs (older group: 46% vs younger group: 28%, P = .06). The composite in-hospital morbidity rate was similar in the older and younger groups. There was no significant difference in the early oxygenation parameters, incidence of acute cellular rejection, or incidence of bronchiolitis obliterans syndrome between the 2 groups. The early survival of the older patients was 95.7% compared with 95.9% in the younger cohort (P = .73). The 1-year survival of the 2 groups was also similar (older group: 79.7% vs younger group: 91.2%, P = .16). The 3-year survival of the older and younger recipients was 73.6% and 74.2%, respectively (P = .64). There were 8 deaths in the older recipient group during the 1-month to 1-year posttransplantation interval, predominantly because of infections. Lung transplantation can be performed in patients older than 65 years with acceptable clinical outcomes. The "increased" mortality of older patients between 1 month and 1 year after transplantation, predominantly from infectious causes, might be due to immunosenescence of older patients. This finding warrants adjustments in the immunosuppression protocol of older patients undergoing lung transplantation. The effect of offering lung transplantation to older patients on donor lung availability deserves further investigation.

Sivelestat Reduces Reperfusion Injury of Lungs Harvested From Endotoxin-primed Rats by Inhibition of Neutrophil-mediated Inflammation

Although liberalization of donor criteria may be one of the solutions to the current serious lung donor shortage, the use of non-standard donor lungs would increase the risk of post-operative complications. In the present study, we investigated the effect of sivelestat, a neutrophil elastase inhibitor, on reperfusion injury of a donor lung that was harvested from endotoxin-primed animals in a rat lung transplantation model. Donor rats received an intraperitoneal injection of Escherichia coli endotoxin (5 mg/kg) 2 hours before lung harvesting. The donor lungs were flushed with an organ preservation solution with or without sivelestat (300 microg/ml), and the left lung was immediately transplanted to the recipient by the cuff technique. Endotoxin priming did not cause significant lung injury before harvesting. Although these lungs looked normal macroscopically, they were found to contain numerous neutrophils in the alveolar capillaries, even after lung flushing. There was no significant difference in the neutrophil count between the lungs flushed with and without sivelestat. The endotoxin-primed donor lung without sivelestat treatment became edematous immediately after reperfusion. In addition, the recipient's native right lungs were also pathologic. Treatment with sivelestat significantly reduced injury in both the donor and the recipient's native lungs. Treatment with sivelestat also inhibited the increase in tumor necrosis factor-alpha and cytokine-induced neutrophil chemoattractant-1 levels in the recipient circulation after reperfusion. We conclude that sivelestat could reduce lung injury after transplantation by inhibiting the deleterious burst of inflammatory reactions that are initiated by reperfusion of the lungs from endotoxin-primed rats.