Donor Organ Quality Research Articles

Improving Outcomes in Bridge-to-Transplant: Extended Extracorporeal Membrane Oxygenation Support to Obtain Optimal Donor Lungs for Marginal Recipients

The use of extracorporeal membrane oxygenation (ECMO) as bridge-to-lung transplantation has been discussed controversially because of discouraging results. We report our experience with this challenging strategy. This retrospective investigation includes all consecutive lung transplantations in our center between January 2012 and July 2017 (n = 88, median Lung Allocation Score 66). Data of patients on ECMO bridge-to-transplant (n = 34) were compared with patients without such support (n = 54). Patients requiring ECMO support underwent lung transplantation after median bridging time of 29 days (range, 0-129 days). Survival was superior if transplantation was performed within 29 days of ECMO (p = 0.04). Donor age and oxygenation (pO2/FiO2) were similar in recipients with ECMO (42.3 ± 15.2 years, 444.5 ± 68.9 mm·Hg) or without ECMO (43.1 ± 13.9 years, 454.5 ± 73.4 mm·Hg). Four patients required postoperative ECMO support >1 day. Survival at 1 year and 3 years was similar in recipients with ECMO support (79%, 63%) or without ECMO support (86%, 71%). Successful lung transplantation after ECMO as bridge-to-transplant can be achieved, even in patients with prolonged support times. Bridging time of less than 30 days, however, is crucial for success. Extracorporeal membrane oxygenation expertise and donor organ quality may be important factors for favorable outcome.

Association of baseline histopathology and kidney donor risk index with graft outcomes indeceased donor kidney transplantation .

Donor organ quality is a key determinant of graft outcomes in deceased donor kidney transplantation (DDKT). The predictive values of baseline histopathology and several clinical scoring systems for long-term graft outcomes have been evaluated, but the results remain controversial. We screened 167 patients who underwent DDKT at Ulsan University Hospital from April 2003 to June 2016. Among them, 66 patients who underwent baseline kidney biopsy and whose kidney donor risk index (KDRI) was available were included in this analysis. All baseline biopsies were rescored according to the updated Banff classification. Median follow-up was 22 months. Mean age of recipients and donors was 51.4 and 44.7 years, respectively. Mean KDRI was 1.40±0.44. During follow-up, delayed graft function and biopsy-proven acute rejection (BPAR) developed in 7 and 11 patients, respectively. Graft failure occurred in 2 patients. In Cox regression analysis, interstitial fibrosis/tubular atrophy (IFTA) (hazard ratio (HR) = 3.59; p=0.049) was a significant risk factor for BPAR. In multivariate linear regression, age (standardized β (SB) = -0.282; p=0.002), BPAR (SB = -0.406; p < 0.001), KDRI (SB = -0.277; p=0.003), and IFTA (SB = -0.298; p=0.001) were significant predictors of last-visit estimated glomerular filtration rate (eGFR). Several clinical and pathologic parameters, such as KDRI and IFTA, may be helpful for predicting long-term graft outcomes, including BPAR and last-visit eGFR, in DDKT. .

Human Hearts Declined for Transplant Were Resuscitated on the Visible Heart® Apparatus

Purpose Improved utilization of donor hearts would benefit chronic heart failure patients awaiting transplant. Limitations to cardiac allograft preservation include ischemic time, donor organ quality, and accurate graft assessment. We hypothesized that human hearts declined for transplant may be resuscitated after varied ischemic times. The unique studies performed within the Visible Heart® Laboratory for over two decades have provided unique insights relative to optimizing large mammalian functions post-cardioplegia. Methods Human hearts declined for transplant were utilized for research at the Visible Heart® Laboratory in coordination with the local organ procurement organization. Donor hearts were procured in standard fashion using 2L cardioplegia solution, and storage on ice. Hearts were delivered within 4-10 hours and cannulated for perfusion in Langendorf, right-sided, or 4-chamber working modes. Next, hearts were perfused with a warmed, oxygenated Kreb-Henseleit perfusate. These hearts were deemed non-viable for transplant for a variety of factors. Hemodynamic parameters, functional endoscopic videos, and electrocardiographic parameters have been recorded. All hearts were perfusion-fixed in formaldehyde and preserved in the Visible Heart® Library. Results Eighty-three human hearts declined for transplant were reanimated on the Visible Heart® Apparatus: varied hemodynamic functions were recorded. Average donor age was 57 years (7 to 91 yrs). Fifty percent (50%) of donors were female. Average cold ischemic time was 402 minutes (126-678 minutes). All hearts achieved pulsatile perfusion, and evidence of EKG rhythm. Conclusion This work demonstrates the unique capabilities of the Visible Heart® Laboratory: the abilities to reanimate human hearts and investigate relative electrophysioligical and hemodynamic behaviors has utility for determining if some human hearts declined for transplant were in fact viable, or could benefit from post-conditoning. Hence, this work provides encouragement for expanding the utilization of donor hearts available for transplant. Future work will focus on improved preservation techniques (i.e., various cardioplegia agents, warm perfusion vs cold storage), novel pharmacologic pre- and post-conditioning agents, and improved assessment of donor hearts during preservation. Improved utilization of donor hearts would benefit chronic heart failure patients awaiting transplant. Limitations to cardiac allograft preservation include ischemic time, donor organ quality, and accurate graft assessment. We hypothesized that human hearts declined for transplant may be resuscitated after varied ischemic times. The unique studies performed within the Visible Heart® Laboratory for over two decades have provided unique insights relative to optimizing large mammalian functions post-cardioplegia. Human hearts declined for transplant were utilized for research at the Visible Heart® Laboratory in coordination with the local organ procurement organization. Donor hearts were procured in standard fashion using 2L cardioplegia solution, and storage on ice. Hearts were delivered within 4-10 hours and cannulated for perfusion in Langendorf, right-sided, or 4-chamber working modes. Next, hearts were perfused with a warmed, oxygenated Kreb-Henseleit perfusate. These hearts were deemed non-viable for transplant for a variety of factors. Hemodynamic parameters, functional endoscopic videos, and electrocardiographic parameters have been recorded. All hearts were perfusion-fixed in formaldehyde and preserved in the Visible Heart® Library. Eighty-three human hearts declined for transplant were reanimated on the Visible Heart® Apparatus: varied hemodynamic functions were recorded. Average donor age was 57 years (7 to 91 yrs). Fifty percent (50%) of donors were female. Average cold ischemic time was 402 minutes (126-678 minutes). All hearts achieved pulsatile perfusion, and evidence of EKG rhythm. This work demonstrates the unique capabilities of the Visible Heart® Laboratory: the abilities to reanimate human hearts and investigate relative electrophysioligical and hemodynamic behaviors has utility for determining if some human hearts declined for transplant were in fact viable, or could benefit from post-conditoning. Hence, this work provides encouragement for expanding the utilization of donor hearts available for transplant. Future work will focus on improved preservation techniques (i.e., various cardioplegia agents, warm perfusion vs cold storage), novel pharmacologic pre- and post-conditioning agents, and improved assessment of donor hearts during preservation.

Complement Therapeutics in the Multi-Organ Donor: Do or Don't?

Over the last decade, striking progress has been made in the field of organ transplantation, such as better surgical expertise and preservation techniques. Therefore, organ transplantation is nowadays considered a successful treatment in end-stage diseases of various organs, e.g. the kidney, liver, intestine, heart, and lungs. However, there are still barriers which prevent a lifelong survival of the donor graft in the recipient. Activation of the immune system is an important limiting factor in the transplantation process. As part of this pro-inflammatory environment, the complement system is triggered. Complement activation plays a key role in the transplantation process, as highlighted by the amount of studies in ischemia-reperfusion injury (IRI) and rejection. However, new insight have shown that complement is not only activated in the later stages of transplantation, but already commences in the donor. In deceased donors, complement activation is associated with deteriorated quality of deceased donor organs. Of importance, since most donor organs are derived from either brain-dead donors or deceased after circulatory death donors. The exact mechanisms and the role of the complement system in the pathophysiology of the deceased donor have been underexposed. This review provides an overview of the current knowledge on complement activation in the (multi-)organ donor. Targeting the complement system might be a promising therapeutic strategy to improve the quality of various donor organs. Therefore, we will discuss the complement therapeutics that already have been tested in the donor. Finally, we question whether complement therapeutics should be translated to the clinics and if all organs share the same potential complement targets, considering the physiological differences of each organ.

Renal effects of exendin-4 in an animal model of brain death

Organ transplantation is the gold standard therapy for the majority of patients with terminal organ failure. However, it is still a limited treatment especially due to the low number of brain death (BD) donors in relation to the number of waiting list recipients. Strategies to increase the quantity and quality of donor organs have been studied, and the administration of exendin-4 (Ex-4) to the donor may be a promising approach. Male Wistar rats were randomized into 3 groups: (1) control, without central nervous system injury; (2) BD induced experimentally, and (3) BD induced experimentally + Ex-4 administered immediately after BD induction. After BD induction, animals were monitored for 6h before blood collection and kidney biopsy. Kidney function was assessed by biochemical quantification of plasma kidney markers. Gene and protein expressions of inflammation- and stress-related genes were evaluated by RT-qPCR and immunoblot analysis. Animals treated with Ex-4 had lower creatinine and urea levels compared with controls. BD induced oxidative stress in kidney tissue through increased expression of Ucp2, Sod2 and Inos, and Ex-4 administration reduced the expression of these genes. Ex-4 also induced increased expression of the anti-apoptotic Bcl2 gene. Nlrp3 and Tnf expressions were up-regulated in the BD group compared with controls, but Ex-4 treatment had no effect on these genes. Our findings suggest that Ex-4 administration in BD rats reduces BD-induced kidney damage by decreasing the expression of oxidative stress genes and increasing the expression of Bcl2.

Subclinical Changes in Deceased Donor Kidney Proteomes Are Associated With 12-month Allograft Function Posttransplantation-A Preliminary Study.

BackgroundCerebral injury during donation after brain death may induce systemic damage affecting long-term kidney function posttransplantation. Conventional evaluation of donor organ quality as a triage for transplantation is of limited utility.MethodsWe compared donor kidneys yielding opposing extremes of the continuum of posttransplantation outcomes by several common kidney biopsy evaluation techniques, including Kidney Donor Profile Index and Remuzzi scoring, and analyzed tissue from a minimal sample cohort using label-free quantitation mass spectrometry. Further assessment of the proteomic results was performed by orthogonal quantitative comparisons of selected key proteins by immunoblotting.ResultsWe show that common evaluation techniques of kidney biopsies were not predictive for posttransplantation outcomes. In contrast, despite the limited cohort size, the proteomic analysis was able to clearly differentiate between kidneys yielding extreme posttransplantation outcome differences. Pathway analysis of the proteomic data suggested that outcome-related variance in protein abundance associated with profibrotic, apoptosis, and antioxidant proteins. Immunoblotting confirmation further supported this observation.ConclusionsWe present preliminary data indicating that there is scope for existing evaluation approaches to be supplemented by the analysis of proteomic differences. Furthermore, the observed outcome-related variance in a limited cohort was supported by immunoblotting and is consistent with mechanisms previously implicated in the development of injury and cytoprotection in kidney transplantation.

Transplantation of expanded criteria kidney grafts to elderly recipients in the N.V. Sklifosovsky Research Institute for Emergency Medicine

Introduction:The expansion of the criteria for donor organ retrieval contributes to an increase in the number of kidney transplantations to elderly recipients; but in view of reduced requirements to donor organ quality, a further analysis of transplantation outcomes is needed. The aim was to analyze and compare the outcomes of kidney transplantation to elderly patients depending on the donor organ quality.Material and methods.The study was based on the analysis of the kidney transplantation outcomes in 61 elderly recipients, including 51 transplantations performed from expanded criteria donors (group 1), and other 10 from standard donors (group 2). Based on clinical, laboratory, histological, and instrumental diagnostic data, we compared the graft function recovery rates, graft/recipient survival rates, the causes of graft loss in the early posttransplant period.Results:Patients of group I had significantly higher delayed graft function rates (37.3% vs. 10%), graft non-function rates (15.7% vs. 0%), and lower early posttransplant survival rates (72.5% vs. 100%). Graft function recovery rate was 58.8% in group I, and 100% in the patients of group II. The most common cause of the graft loss and the renal graft removals performed in the early posttransplant period was the poor graft quality due to the donor's existing pathology.Conclusion.The study demonstrated a statistically significant deterioration of the initial graft function, significantly increased graft non-function rates, and decreased graft survival rates in the early posttransplant period in the elderly recipients after kidney transplantation from expanded criteria donors.

Additional value of smartphone video recordings for the assessment of donor organ quality for liver transplantation

Additional value of smartphone video recordings for the assessment of donor organ quality for liver transplantation

Dutch Law Approves Opt-out System.

Dutch Law Approves Opt-out System.

Outcome of Overseas Kidney Transplantation Among Azerbaijani Patients

Background Kidney transplantation is an effective treatment option for patients with end stage renal disease (ESRD). Despite of increase of number of renal transplantation in recent years in Azerbaijan, absence of deceased organ transplantation programs and malfunctioning of the local programs make patients go for transplantation at transplant centres outside country. In this study, our aim is to investigate the results of kidney transplantation in Azerbaijani patients who travel abroad for organ transplantation. Methods Retrospective chart review of the patients who underwent kidney transplantation outside Azerbaijan was used to assess clinical outcomes during a period of 18 years. This is a quantitative, cross-sectional, descriptive study based on data collected through document analysis and systematic review. The data was obtained from Medservice Medical Centre of Azerbaijan. Results We studied data from 300 patients in detail. Among the total of 300 patients, 199 (66.3%) were male and 101 (33.6%) were female with a male female ratio of 1.97:1. Mean age of the patients was 43+/-11.3 years. Only 25 patients (8.3 %) were transplanted in Azerbaijan. The vast majority of patients (275 (91.7%)) underwent kidney transplantation outside the country. Among the total of 300 transplantations, 209 (69.6%) were done in Iran Islamic Republic. This were followed by 19 (6.3%) in Georgia, 15 (5%) in Turkey, 6 (2%) in Russian Federation, 7 (2.3%) in Pakistan, 4 (1. 3%) in Tajikistan. Of these 300 patients, only 23 patients received induction immunosuppressive therapy. Overall, one year graft and patient survival rates were 91% and 95% respectively. The episodes of acute rejection occurred in 26 of the 300 patients. Complications were mainly due to the infections causing potentially life-threatening illnesses in 23 post-transplant patients. 13 patients developed septic shock and died. Conclusions Overall patient and graft survival outcomes were not good after overseas kidney transplantation and there were considerable variations in survival rates between countries. Although improper follow-up was a main factor, other problems such as incomplete preoperative preparation and poor donor organ quality also had great impact on postoperative complications and graft survival rates.

Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function

Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.

Prolonged Management in Donors with Reduced Ejection Fraction is a Risk Factor for Graft Loss in Pediatric Heart Transplantation

Donor brain death is believed to cause a cascade of events which may impact the quality and immune activation of donor organs. While the need for expanding the donor pool is pressing, conflicting evidence exists on the use of cardiac donors with reduced ejection fraction (EF). We sought to evaluate reduced EF donor hearts and the relationship between brain death interval (BDI) and pediatric recipient and graft survival.

Organ preservation: from the past to the future.

Organ transplantation is the most effective therapy for patients with end-stage disease. Preservation solutions and techniques are crucial for donor organ quality, which is directly related to morbidity and survival after transplantation. Currently, static cold storage (SCS) is the standard method for organ preservation. However, preservation time with SCS is limited as prolonged cold storage increases the risk of early graft dysfunction that contributes to chronic complications. Furthermore, the growing demand for the use of marginal donor organs requires methods for organ assessment and repair. Machine perfusion has resurfaced and dominates current research on organ preservation. It is credited to its dynamic nature and physiological-like environment. The development of more sophisticated machine perfusion techniques and better perfusates may lead to organ repair/reconditioning. This review describes the history of organ preservation, summarizes the progresses that has been made to date, and discusses future directions for organ preservation.

Invited Commentary

Invited Commentary

When the momentum has gone: what will be the role of extracorporeal lung support in the future?

There has been expanding interest in and use of extracorporeal support in respiratory failure concurrent with technological advances and predominantly observational data demonstrating improved outcomes. However, until there is more available data from rigorous, high-quality randomized studies, the future of extracorporeal support remains uncertain. Outcomes for patients supported with extracorporeal devices continue to show favorable trends. There are several large randomized controlled trials that are in various stages of planning or completion for extracorporeal membrane oxygenation (ECMO) and extracorporeal carbon dioxide removal (ECCO2R) in the acute respiratory distress syndrome (ARDS) and chronic obstructive pulmonary disease (COPD), which may help clarify the role of this technology for these disease processes, and which stand to have a significant impact on a large proportion of patients with acute respiratory failure. Novel applications of extracorporeal lung support include optimization of donor organ quality through ex-vivo perfusion and extracorporeal cross-circulation, allowing for multimodal therapeutic interventions. Despite the ongoing rise in ECMO use for acute respiratory failure, its true value will not be known until more information is gleaned from prospective randomized controlled trials. Additionally, there are modalities beyond the current considerations for extracorporeal support that have the potential to revolutionize respiratory failure, particularly in the realm of chronic lung disease and lung transplantation.

The Number of Refusals for Donor Organ Quality Does Not Impact Heart Transplant Outcomes in Children

Waitlist mortality is more than 12% for pediatric heart transplantation, with strikingly high rates of organ refusal, many of which are due to donor quality. However, some centers use these organs despite refusals by other centers for donor quality. We hypothesize that the number of refusals for donor quality (RDQ) does not affect pediatric heart transplantation outcomes. Pediatric heart transplants from 2000 to 2015 were identified using the United Network for Organ Sharing database and were matched against the potential transplant recipients dataset with donor refusal codes. Refusals for donor quality were counted for each organ. The population was divided into two groups: RDQ-low (0 to 3 RDQs, n= 3,404) and RDQ-high (>3 RDQs, n= 1,585). Posttransplant outcomes of both cohorts were analyzed. Of 4,989 pediatric heart transplants, 75% (n= 3,770) had 1 or more RDQ (median 3 RDQ; interquartile range, 1 to 7). The RDQ-lower group (0 to 3 RDQs) and the RDQ-higher group (>3 RDQ) had similar posttransplant survival (p= 0.41) and freedom from retransplantation (p= 0.37). Both groups had similar posttransplant survival even for high-risk recipient cohorts: adolescents (p= 0.06), congenital heart disease (p= 0.87), retransplantation (p= 0.47), extracorporeal membrane oxygenation (p= 0.61), mechanical ventilation (p= 0.24), and poor renal function at transplant (p= 0.46). In addition, recipient subgroups who had donors with increasing number of RDQ (>6, >9, >12, and >15 RDQ) also had similar posttransplant survival compared with the RDQ-low group (p= 0.63, p= 0.62, p= 0.92, and p= 0.50, respectively). The outcome of pediatric heart transplantation is not affected by the number of RDQ, even for high-risk recipients. The use and interpretation of donor quality refusal code should be considered carefully while selecting or refusing donors in this era of supply and demand mismatch.

Does Kidney Donor Risk Index implementation lead to the transplantation of more and higher-quality donor kidneys?

BackgroundThe Kidney Donor Risk Index (KDRI) is a quantitative evaluation of the quality of donor organs and is implemented in the US allocation system. This single-centre study investigates whether the implementation of the KDRI in our decision-making process to accept or decline an offered deceased donor kidney, increases our acceptance rate.MethodsFrom April 2015 until December 2016, we prospectively calculated the KDRI for all deceased donor kidney offers allocated by Eurotransplant to our centre. The number of the transplanted versus declined kidney offers during the study period were compared to a historical set of donor kidney offers.ResultsAfter implementation of the KDRI, 26.1% (75/288) of all offered donor kidneys were transplanted, compared with 20.7% (136/657) in the previous period (P < 0.001). The median KDRI of all transplanted donor kidneys during the second period was 0.97 [Kidney Donor Profile Index (KDPI) 47%], a value significantly higher than the median KDRI of 0.85 (KDPI 34%) during the first period (P = 0.047). A total of 68% of patients for whom a first-offered donor kidney was declined during this period were transplanted after a median waiting time of 386 days, mostly with a lower KDRI donor kidney.ConclusionsImplementing the KDRI in our decision-making process increased the transplantation rate by 26%. The KDRI can be a supportive tool when considering whether to accept or decline a deceased donor kidney offer. More data are needed to validate this score in other European centres.

The Impact of Duration of Brain Death on Outcomes in Abdominal Organ Transplantation

Background Brain death (BD) induces a profound inflammatory response affecting the quality and function of donor organs. Longer BD duration increases injury in donor organs, but up-regulation of defence mechanisms also occurs, initiating regeneration and repair. This poses the question what is better for the graft-to-be: retrieval of the organs as-soon-as-possible or wait and optimise in-situ repair? Methods A retrospective analysis of the UK transplant registry evaluated donors after brain death DBD donors during 2008-2012. In 1881 donors the relationship between BD duration and function or graft-survival at 1 and 3-years was analysed using multivariate and Cox regression analyses of 2815 kidneys, 1555 livers and 588 pancreata. Results Longer BD duration did not have a detrimental association with liver transplant survival (p = 0.89, 1 yr survival), whilst in fact prolonged BD duration was associated with increased transplant survival following first kidney-only transplantation (p = 0.02, 1 yr survival) for prolonged cold ischaemic time (18-24 hours) and following pancreas transplantation (p < 0.0001, 1 yr survival) in recent years. Although delayed graft function was more common in kidney transplants as the duration of BD increased (p < 0.0001), there was no association with primary non-function (p = 0.62). Longer BD duration had no detrimental association with graft function at 1 year when the donor was 30 years or older and was associated with increased graft function for donors aged 30 to 40 years (p = 0.01). Discussion This demonstrates that prolonged BD is not detrimental to outcomes in abdominal organ transplantation. This finding supports that time for donor management may be effectively used to adequately optimise donor organs. This analysis renounces the need for a ‘Rush and Retrieve’ policy and suggests that the DBD environment may be less ‘hostile’ than is perceived, allowing sufficient time to support repair through targeted intervention prior to organ retrieval.

UK Donation Ethics Committee Response to the New South Wales Consultation on Ante-Mortem Interventions for Organ Donation

This is a response to the New South Wales consultation on ante-mortem interventions for organ donation submitted on behalf of the former members of the UK Donation Ethics Committee (UKDEC), UKDEC was an independent body, hosted by the Academy of Medical Royal Colleges, and funded by all four UK Health Departments. UKDEC’s role was to consider ethical issues relating to the field of organ donation and transplantation and to provide independent advice to clinicians, policy leads and others. The NSW Discussion Paper assumes that ante-mortem interventions cannot be authorised using the Guardianship Act 1987, s.32 standard for decision-making, i.e. promoting and maintaining the patient’s health and well-being. In the response we argue that provisions in the Guardianship Act and their judicial interpretation appear to leave room for arguments that non-therapeutic medical interventions such as ante-mortem interventions to optimise donor organ quality and improve transplant outcomes could be permitted under the Act if they are in the patient’s best interests, interpreted broadly to include emotional, psychological and social interests, although an amendment to s.46 of the Act would make this clearer. In our view, the use of the Guardianship Act 1987 to make a best interests decision for the patient is to be preferred to the proposed amendment of the Human Tissue Act 1983 to permit the senior next of kin to consent to ante-mortem interventions. The latter proposal contains no standard of decision-making (for example, best interests), so senior next of kin could consent to ante-mortem interventions which are not in the patient’s best interests. The retention of ante-mortem decision-making under the Guardianship Act 1987 would achieve greater consistency and protect the patient from abuse or exploitation, as required by s.4(g). Moreover, it would avoid the use of ‘special rules’ for decisions at the end of potential organ donors’ lives, and the risk of damaging public confidence in organ donation and discouraging the registration of consent to donation.

Evaluation of Gene Expression Pattern of IL1B and IL10 Cytokines Following Vitamin C Administration among Brain-Dead Liver Donors

Background: Inflammatory events following brain death (BD) decrease the quality of donor organs which can affect the outcome of the transplantation. It experimentally and clinically is verified that the level of inflammatory cytokines is increased in the BD of the donor results. In experiments, the in vitro use of vitamin C can successfully decrease the levels of inflammatory cytokines. Objectives: The aim of this study was to investigate the influence of vitamin C administration on the inflammatory status of the graft in BD liver donors. Methods: This study was conducted at Nemazee Hospital’s transplant center (Shiraz, Iran). In this interventional study, the BD liver donors (n = 40) were randomly divided into two groups. The control group received only the routine intensive care unit (ICU) considerations, and the intervention group was treated with Vitamin C before harvesting organ (100 mg/kg, initially followed by 100 mg/kg/6h until organ removal). Blood samples were taken from BD patients in the intervention and control groups 3 times: 6 hours before operation, immediately after laparotomy, and immediately prior to clamping the aorta to assess the gene expression ratio of Interleukin 1 beta (IL1B) and Interleukin 10 (IL10) cytokines using real time polymerase chain reaction (PCR) (n = 40). Soluble serum cytokines were measured by enzyme-linked immunosorbent assay (ELISA) (n = 24). Results: No significant differences were observed in mRNA expression ratio of IL1B and IL10 between two groups. Despite an acceptable decrease in serum concentration of the inflammatory markers IL1B and IL10 at time point 2 minus time point 1 (T2-1), no significant differences were observed in vitamin C-treated BD donors compared with the control donors. There was a significant difference among aspartate aminotransferase (AST) and alanine aminotransferase (ALT) changes on the 3rd to 1st days after operation between the control and intervention recipients (P < 0.05). Conclusions: The present study suggests a beneficial effect of vitamin C adsministration on post-transplant function of the liver from BD liver donors.