First Week Of Transplantation Research Articles

Critical Care Length of Stay and Support Requirements for Patients Postpancreas Transplant.

Introduction: Pancreas transplant is one of the UK's less commonly done solid abdominal organ transplants. The transplant is reputed for its high-risk postsurgical complications due to multiple patients, procedures, and immunological factors. For this reason, patients are habitually admitted to the intensive care unit for postlaparotomy care, physiological support, and graft function monitoring during their immediate postoperative course. Project Aim: This program evaluation analyzed the trend in critical care length of stay and organ support requirements for patients following whole pancreas transplantation. The aim was to use these baseline data as performance metrics to enable a safer transition and Plan-Do-Study-Act (PDSA) cycles in improving the delivery of enhanced recovery service. Design: A retrospective chart review was performed using records from Phillips IntelliSpace Critical Care and Anaesthesia system to evaluate the institutional outcomes of patients < 18 years admitted to intensive care following pancreas transplantation between January 1, 2018, and December 31, 2021. Islet-cell transplant recipients were excluded as there is a different postoperative recovery. Results: The data suggested that although patients require a higher level of observations, blood pressure management, blood gas, and glucose monitoring during their first week of transplant, these patients did not routinely require the full range of critical care support. Conclusion: The present evaluation reported the organ support requirements for these transplant recipients. The results will generate further interest in enhanced recovery and service evaluation projects to streamline the postoperative care of these patients from the operating theatre back to the transplant wards.

Frequency of New Onset Diabetes Mellitus in Patients with Live Related Renal Transplant

Background: Kidney transplant is only the cure of end stage renal diseases. It is because it provides the maximum replacement of renal functions. New onset diabetes after transplantation is one of the serious and chronic problem of renal transplant. NODAT is reported to occur in 4%-25% of renal transplant recipients. New onset diabetes may be identified after the renal transplant at any time. Objective: The study aimed to determine the frequency of new onset of diabetes mellitus in the patients with live related renal transplant. Study design: It is a retrospective study conducted in the department of nephrology and transplantation, Pir Abdul Qadir Shah Jeelani Institute of Medical Sciences, Gambat for the duration of six months from July 2022 to December 2022. Material and Methods: There were 50 patients in PTDM group and 70 were in the non PTDM group. The anthropometric and clinical characteristics were recorded. The SPSS software was used for the analysis. The Patients were divided into two groups according to the diagnosis. Results: The average age of patients in PTDM group is 43.2 years whereas in non-PTDM group the average age is 45 years. Statistical analysis revealed that results are statistically significant with 95% CI. Most of the cases appeared during 2 weeks of transplant however, 14 patients also reported about diabetes after 2 months of transplant. Conclusion: Common metabolic disease PTDM is usually diagnosed during first 6 weeks of renal transplantation. Old age, family history of diabetes, the presence of IGF during first week of transplantation are some of the risk factors that lead to PTDM prevalence. The PTDM was observed in the 40% patients in our study. Keywords: renal functions and post-transplant diabetes mellitus.

Effect of regulatory T cells on short-term graft outcome in kidney transplant recipients, a prospective observational, single-center study

BackgroundRegulatory T cells (Tregs) are important for maintaining immune homeostasis, limiting kidney transplant rejection, and promoting transplant tolerance. Tregs are characterized as CD4 + CD25+ T cells and the transcription factor Foxp3; they constitute 5–10% of all peripheral CD4+ T cells in healthy humans. The reduction in Treg cells after transplantation may be a predictive factor in graft rejection. Therefore, in this study, we investigated the association between Tregs and short-term graft outcomes in renal transplant recipients. MethodsThis prospective observational study included 50 patients of both sexes, aged between 18 and 60 years, with end-stage renal disease (ESRD), and who underwent kidney transplantation at the Nizams Institute of Medical Sciences. Flow cytometry was used to measure the percentage of Tregs (CD4 + CD25+) pre-transplant (baseline) and monthly post-transplant in 50 transplant recipients and 20 healthy controls (HC) over six months. The correlation between Treg percentages and graft outcomes was analyzed. ResultsThe percentage of Tregs (Treg%) was significantly lower in ESRD patients before transplantation (baseline) than in the HCs [median 8.5% vs. 14.25%; p < 0.01]. After transplantation, Treg% decreased significantly within a week after grafting compared to the baseline pre-transplant level [median 5.13% vs. 8.5%; p < 0.01]. Moreover, Treg% was lower in the older (> 40 years) than that in the younger age group at one week after transplantation (p > 0.001). Treg% (CD4 + CD25+) was significantly lower in patients with deceased donor renal transplantation (DDRT) than in live renal transplantation (LRT) within the first week of transplantation [median 2.16% vs. 4.6%; p < 0.05] and at the time of graft rejection [median 3.2% vs. 9.2%; p < 0.001]. Induction therapy with anti-IL-2 receptor monoclonal antibody (IL-2RB) lowered Tregs to a greater extent than anti-thymoglobulin (ATG) therapy and no induction therapy [median 3.22% vs. 5.47%, 8.4%, p < 0.05]. In contrast, an increased Treg% was observed in transplant recipients with normal kidney graft function within six months after transplantation compared with the pre-transplant baseline level [median 11.54% vs. 8.5; p < 0.001]. ROC analysis of graft rejection resulted in an area under the curve (AUC) of 0.8 with a p-value <0.05. ConclusionWithin the first week after transplantation, the percentage of pre-transplant Tregs was significantly decreased compared to that in age- and sex-matched HC. The percentage of Tregs was also lower in patients with advanced age, DDRT, and those who received IL-2RB induction therapy. Patients who experienced graft rejection had lower Treg% compared to their pre-transplant levels. In contrast, patients with normal graft function at six months showed increased Treg%. Together, these results suggest that Treg% measurements are correlated with clinical outcomes.

The Toxicity of Corticosteroids

Minimization of steroid therapy has always been one of the main objectives of immunosuppressive protocols after kidney transplantation, due to numerous side effects. The use of a further reduced daily dose of steroids is considered by many to be a fair compromise between toxicity and efficacy. Unfortunately, the great inter-individual variability of the pharmacokinetics of steroids does not prevent the appearance of major side effects in a variable percentage of patients, even with the low dose used. A drug interaction between steroids and drugs used after transplantation can also contribute to increasing daily exposure to the drug. Steroid discontinuation is still the only procedure capable of achieving the desired goal. This procedure is associated with a greater risk of acute rejection, without however reducing the survival of the transplant. It should be offered to patients at low immunological risk. Early discontinuation, during the first week of transplantation, is also the modality suggested by some guidelines, although a later suspension also offers excellent results. Induction therapy is always recommended in the case of early discontinuation.

Clinical Correlates and Outcomes of Dual Basiliximab and Antithymocyte Globulin Induction in Kidney Transplant Recipients: A National Study.

We used national transplant registry data to study clinical correlates and outcomes of single versus dual induction therapy in adult kidney-only transplant recipients in the United States (2005-2018). The risk of death and graft loss at 1 and 5 y, according to induction therapy type, was assessed using multivariate Cox regression analysis (adjusted hazard ratio with 95% upper and lower confidence limits [LCLaHRUCL]). Of the 157 351 recipients included in the study, 67% were treated with ATG alone, 29% were treated with IL2rAb alone, and 5% were treated with both. Compared with IL2rAb alone, the strongest correlates of dual induction included Black race, calculated panel reactive antibody ≥80%, prednisone-sparing maintenance immunosuppression, more recent transplant eras, longer cold ischemia time, and delayed graft function. Compared with ATG alone, dual induction was associated with an increased 5-y risk of death (aHR 1.071.151.23; P < 0.0001), death-censored graft failure (aHR 1.051.131.22; P < 0.05), and all-cause graft failure (aHR 1.061.121.18; P < 0.0001). Further research is needed to develop risk-prediction tools to further inform optimal, individualized induction protocols for kidney transplant recipients.

POS-770 “SLOW AND STEADY MAY NOT ALWAY WIN THE RACE “ –SHORT TERM OUTCOMES OF SLOW GRAFT FUNCTION POST RENAL TRANSPLANT - A SINGLE CENTRE EXPERIENCE

It is well established that delayed graft function (DGF), traditionally defined as the requirement of dialysis within the first week of transplant, is associated with poorer graft outcomes as compared to immediate graft function (IGF). A subset of patients do not have immediate graft function, but rather have a slower decrease in serum creatinine, not requiring dialysis, termed as slow graft function. Outcomes of this group of patients have not often been studied and most studies have classified this group of patients as having Immediate graft function (IGF) for comparison with patients with DGF. Our aim was to assess short term outcomes of these patients with slow graft function and to identify risk factors, if any among the cohort. Study setting: Kasturba Medical College, Manipal, a tertiary care centre in South India providing healthcare services to a predominantly rural population Type of study: Retrospective, ObservationalStudy Period: January 2016 to April 2018 Sample Size: 70 Renal allograft recipients Slow graft function was defined as per previous studies as follows 1)Creatinine > 3 mg/dl at Post-op day 5 or > 2.5mg/dl at day 72)Creatinine >1.5 and creatinine reduction ratio (CRR) < 20% between Post-op day 1 and post-op day 3Patients with DGF were not included in this study. Demographics related to recipient and donor, biopsy-proven acute rejections, short term outcomes in terms of graft function(serum creatinine and eGFR) at 1 year and 2 years follow up were documented and analysed. The transplants were predominantly living donor ( 88.6% ) and ABO compatible ( 97.1%) with a median follow up of 30 months (IQR 25-40) . 27 out of 70 transplanted patients (38.6%) were characterized as having slow graft function (SGF) as per the definitions and criteria used from earlier studies (Table 1: Baseline characteristics) . On univariate analysis, patients with SGF had lower GFR at 1 year (p-value – 0.028), higher number of biopsy-proven acute rejections over the median follow up period ( 48.1% versus 25.5 %; p-value – 0.039). The number of transplant patients with graft dysfunction at 1 year ( eGFR <60 ml/min) and 2 years were also statistically significant (Table 2: Univariate Analysis). Donor age and donor GFR ( measured by DTPA) were not significantly associated with SGF though numerically median donor age was higher and donor GFR was lower. The subset of patients with SGF may have adverse short term outcomes as compared to those with immediate graft function. A higher incidence of biopsy-proven rejection and higher number of patients with graft dysfunction at 2 years was seen in this cohort. Long term outcomes assessment and identification of risk factors leading to SGF needs to be studied and may help to better risk stratify and manage these patients for better outcomes.

Outcomes of delayed graft function in deceased donor kidney transplantation: a single center experience

Objective: Delayed graft function (DGF) is related to enhanced acute rejection attacks in the short term and reduced graft survival and reduced overall survival in the long-term. In this study, we desired to ascertain the outcomes of DGF. Material and Methods: This study is a retrospective cohort study. Two hundred seventy-four patients who underwent a kidney transplant from a deceased donor were included. DGF was described as obtaining dialysis treatment within the first week of transplant. The kidney recipients were divided into groups DGF+ (Group 1) and DGF- (Group 2). Two groups were compared in terms of risk factors which were based on donor and recipient characteristics. Short-term outcomes, long-term graft survival and recipient survival results were compared. Results: The incidence of DGF was 50.3%. The rate of donors with expanded criteria donor (ECD) was 37.3%. Mean glomerular filtration rate (GFR) at one year after kidney transplantation was 57.5 ml/dk/1.73m2 for Group 1, and 73 ml/dk/1.73m2 for Group 2 (p&amp;lt;0.001). There was no statistically significant difference between the groups in terms of graft loss and mortality at one year. There was no statistically significant difference between groups in terms of graft and recipient survival. Conclusion: DGF did not negatively impact graft survival and recipient survival at one year and long-term, although it was associated with prolonged hospitalization and increased acute rejection in the early period.

Unexpected success in early post-transplantation renal vein thrombosis: A case report and literature review

Background: Allograft renal vein thrombosis can cause graft loss during the early postoperative period. This diagnosis is sometimes elusive, requiring a strong suspicion. On the other hand, several authors have recognized risk factors for allograft renal vein thrombosis, but neither a preventive approach nor a treatment have been recommended for this complication. Case presentation: We present a case report of early allograft renal vein thrombosis, preceded by femoral common deep vein thrombosis in a recipient of a third kidney transplant. Despite femoral common deep vein thrombosis treatment with low-molecular-weight heparin and progressive improvement of renal function to a nadir serum creatinine of 0.51 mg/dL, the patient experienced a sudden episode of anuria on postoperative day 5. Doppler ultrasonography strongly suggested the diagnosis of allograft renal vein thrombosis. The patient underwent balloon catheter and aspiration venous thrombectomy, followed by unfractionated heparin perfusion. After 4 days of anuria and multiple blood transfusions, when allograft nephrectomy was contemplated, diuresis suddenly resumed. After 1 year of follow-up, the patient still has a normal renal function. Conclusion: This case report shows successful treatment of allograft renal vein thrombosis associated with deep vein thrombosis in the first week of transplantation, using balloon catheter and aspiration venous thrombectomy followed by perfusion of unfractionated heparin. The authors suggest this technique as a treatment option for transplant renal vein thrombosis. However, they reinforce the importance of individualized treatment and they remind that a delay may jeopardize the potential benefit of the procedure.

Predictors of Delayed Renal Graft Function in Combined Heart and Kidney Transplant Recipients

Combined heart and kidney transplant has a protective effect on the cardiac graft. We set out to assess the impact of donor, recipient and transplant characteristics on post-transplant renal graft function. We evaluated combined heart-kidney transplant recipients at a single high volume transplant center between March 2012 and December 2017. Recipients with primary cardiac graft dysfunction were excluded. The primary outcome was delayed renal graft function (DRGF) as defined by need for dialysis within the first week of transplantation. The secondary outcome was any dialysis requirement within the first year. A univariate logistic regression model was used to assess the association between the donor, recipient and transplant factors with the primary and secondary outcomes. We identified 66 combined heart-kidney transplant recipients for analysis. Elevated recipient creatinine prior to transplant was associated with DRGF (OR 1.80, 95% 1.25-2.59, p = 0.002). The remainder of evaluated donor and recipient factors were otherwise not associated with acute renal dysfunction (Table 1). Elevated pre-transplant creatinine (OR 1.73, 95% 1.21-2.50, p = 0.003) and redo transplantation (OR 5.70, 95% 1.05-30.87, p = 0.043) were associated with needing dialysis within the first year after transplant (Table 2). In our high volume single center experience of combined heart and kidney transplantation, recipient creatinine prior to transplant was the biggest predictor of primary renal graft failure. In addition, redo heart transplantation increases risk of dialysis within the first year.

Predictors of Renal Graft Failure in Heart/Kidney Transplant Recipients

Combined heart and kidney transplantation have a protective effect on the cardiac graft. Little is known about the factors that impact renal graft function post-transplant. We set out to assess the impact of donor, recipient and transplant characteristics on post-transplant renal graft function. We evaluated combined heart-kidney transplant recipients at a single center from March 2012 to December 2017. Recipients with primary cardiac graft dysfunction were excluded. The primary outcome was delayed renal graft function (DRGF) as defined by need for dialysis within the first week of transplantation. The secondary outcome was any dialysis requirement within the first year. A univariate logistic regression model was used to assess the association between the donor, recipient and transplant factors with the primary and secondary outcomes. We identified 66 combined heart-kidney transplant recipients for analysis. Elevated recipient creatinine prior to transplant was associated with DRGF (OR 1.80, 95% 1.25-2.59, p = 0.002). Other evaluated donor and recipient factors were otherwise not associated with acute renal dysfunction (Table 1). Elevated pre-transplant creatinine (OR 1.73, 95% 1.21-2.50, p = 0.003) and redo transplantation (OR 5.70, 95% 1.05-30.87, p = 0.043) were associated with needing dialysis within the first year after transplant (Table 2). In our single center experience of combined heart and kidney transplantation, recipient creatinine prior to transplant was the biggest predictor of primary renal graft failure. In addition, redo heart transplantation increases risk of dialysis within the first year.

Comparison of the Outcome of Kidney Transplant After Pulsatile or Continuous Ex Vivo Hypothermic Machine Perfusion of Kidneys Donated After Cardiac Death: Analysis of Kidney Pairs

BackgroundHypothermic machine perfusion is used to improve renal perfusion and reduce the rate of early and late graft dysfunction. It has been used in our unit since 2001. It has 2 modes of flow: continuous or pulsatile. The aim of this study is to compare the modes of perfusion in terms of perfusion-related parameters, graft survival, and estimated glomerular filtration rate. MethodsAll donation after cardiac death kidneys between 2002 and 2014 were reviewed. A total of 64 pairs of kidneys were identified of which one kidney underwent pulsatile and the other continuous perfusion. Machine parameters including resistance and perfusion flow index levels at 0, 1, 2, 3, and 4 hours were recorded and glutathione S-transferase was measured in perfusate. Estimated glomerular filtration rate from the first week of transplant until the fifth year and graft survival rates were determined. ResultsMachine parameters were similar at all time points. Estimated glomerular filtration rates and graft survival were the same irrespective of perfusion mode. ConclusionPulsatile perfusion may be regarded as more physiological. However, we could not identify difference in outcome following transplant of kidneys from the same donor that had been perfused under pulsatile or continuous conditions.

Peritoneal dialysis catheter removal at the time of renal transplantation: Choosing the optimal candidate.

Concurrent peritoneal dialysis (PD) catheter removal during renal transplantation is controversial, with limited evidence supporting this practice. Our objective was to determine the rate of delayed graft function (DGF) in patients on preoperative PD. Additionally, we sought to identify which patients can safely have their PD catheter removed during transplantation due to a low risk of DGF. We conducted a retrospective observational study between June 2011 and December 2015. The primary outcome was the diagnosis of DGF, defined as the need for dialysis within the first week of transplantation. Clinical and transplant factors, including graft type and donor criteria, were assessed for association with the primary outcome. Catheter-related complication rates were also compared between post-transplant PD and hemodialysis (HD). Of our cohort of 567 patients, 145 patients (25.6%) developed DGF. Obesity (odds ratio [OR] 1.06; 95% confidence interval [CI] 1.00-1.11; p=0.04) and increased perioperative blood loss (OR 1.002; 95% CI 1.000-1.003; p=0.03) were predictors of DGF. Protective factors included living donor (LD) grafts (OR 0.15; 95% CI 0.05-0.49; p=0.002) and intraoperative graft urine production (OR 0.39; 95% CI 0.23-0.65; p<0.001). In our PD cohort, only LD grafts demonstrated lower DGF rates (0 LD vs. 20.8% deceased donor; p=0.003). In terms of post-transplant renal replacement therapy, patients on PD and HD had similar duration of temporary dialysis (one day PD vs. two days HD; p=0.48) and catheter-related complication rates (4.5% PD vs. 2.6% HD; p=0.30). Carefully selected patients, such as those receiving LD grafts, may benefit from concurrent PD catheter removal.

Microporous polymer scaffolds that control innate immunity for enhanced islet transplant

Event Abstract Back to Event Microporous polymer scaffolds that control innate immunity for enhanced islet transplant Michael Gower1, Jeffrey Liu2 and Lonnie D. Shea2 1 University of South Carolina, Chemical Engineering, United States 2 University of Michigan, Biomedical Engineering, United States Biomaterial scaffolds are central to many regenerative strategies as they create a space for infiltration of host tissue and provide a platform to deliver growth factors and progenitor cells. However, biomaterial implantation results in an unavoidable inflammatory response that impairs tissue regeneration and promotes loss or dysfunction of transplanted cells. Porous poly (lactide-co-glycolide) (PLG) scaffolds have been developed that provide a platform for islet transplant, reversing diabetes with a fraction of the islets isolated from a healthy mouse pancreas. However, transplant of allogeneic and xenogeneic tissue, which is of clinical relevance, requires the control of immunity by immunosuppressive drugs. We investigated localized delivery of immunomodulatory factors to control the immune environment around biomaterial scaffolds and transplanted cells. Scaffolds designed to release IL-10, TGF-β1, CCL22, and resveratrol were implanted into intraperitoneal fat, a site frequently used for cell transplantation. Expression of cytokines including TNF-α, IL-12, and MCP-1 and immune cell infiltration into the implant site were monitored by ELISA and flow cytometry, respectively. Implant of scaffolds that released IL-10 and TGF-β1, significantly decreased the inflammatory response to scaffold implant. Transplantation of islets into diabetic mice on TGF-β1 scaffolds significantly improved the ability of syngeneic islets to control blood glucose levels within the first week of transplant and delayed rejection of allogeneic islets. Together, these studies emphasize the ability of localized TGF-β1 delivery to modulate the immune response to biomaterial implant and enhance cell function in cell-based therapies. Keywords: Regenerative Medicine, Scaffold Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Biomaterials in immune response Citation: Gower M, Liu J and Shea LD (2016). Microporous polymer scaffolds that control innate immunity for enhanced islet transplant. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02220 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Michael Gower Jeffrey Liu Lonnie D Shea Google Michael Gower Jeffrey Liu Lonnie D Shea Google Scholar Michael Gower Jeffrey Liu Lonnie D Shea PubMed Michael Gower Jeffrey Liu Lonnie D Shea Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Transforming growth factor-beta 1 delivery from microporous scaffolds decreases inflammation post-implant and enhances function of transplanted islets

Biomaterial scaffolds are central to many regenerative strategies as they create a space for infiltration of host tissue and provide a platform to deliver growth factors and progenitor cells. However, biomaterial implantation results in an unavoidable inflammatory response, which can impair tissue regeneration and promote loss or dysfunction of transplanted cells. We investigated localized TGF-β1 delivery to modulate this immunological environment around scaffolds and transplanted cells. TGF-β1 was delivered from layered scaffolds, with protein entrapped within an inner layer and outer layers designed for cell seeding and host tissue integration. Scaffolds were implanted into the epididymal fat pad, a site frequently used for cell transplantation. Expression of cytokines TNF-α, IL-12, and MCP-1 were decreased by at least 40% for scaffolds releasing TGF-β1 relative to control scaffolds. This decrease in inflammatory cytokine production corresponded to a 60% decrease in leukocyte infiltration. Transplantation of islets into diabetic mice on TGF-β1 scaffolds significantly improved the ability of syngeneic islets to control blood glucose levels within the first week of transplant and delayed rejection of allogeneic islets. Together, these studies emphasize the ability of localized TGF-β1 delivery to modulate the immune response to biomaterial implants and enhance cell function in cell-based therapies.

The role of brain-derived neurotrophic factor in bone marrow stromal cell-mediated spinal cord repair.

The ability of intraspinal bone marrow stromal cell (BMSC) transplants to elicit repair is thought to result from paracrine effects by secreted trophic factors including brain-derived neurotrophic factor (BDNF). Here we used gene therapy to increase or silence BDNF production in BMSCs to investigate the role of BDNF in BMSC-mediated neuroprotection. In a spinal cord organotypic culture, BMSC-conditioned medium significantly enhanced spinal motoneuron survival by 64% compared with culture medium only. Only conditioned medium of BDNF-hypersecreting BMSCs sustained this neuroprotective effect. In a rat model of spinal cord contusion, a BDNF-dependent neuroprotective effect was confirmed; only with a subacute transplant of BDNF-hypersecreting BMSCs were significantly more spared motoneurons found at 4 weeks postinjury compared with vehicle controls. Spared nervous tissue volume was improved by 68% with both control BMSCs and BDNF-hypersecreting BMSCs. In addition, blood vessel density in the contusion with BDNF-hypersecreting BMSCs was 35% higher compared with BMSC controls and sixfold higher compared with vehicle controls. BDNF-silenced BMSCs did not survive the first week of transplantation, and no neuroprotective effect was found at 4 weeks after transplantation. Together, our data broaden our understanding of the role of BDNF in BMSC-mediated neuroprotection and successfully exploit BDNF dependency to enhance anatomical spinal cord repair.

PTH-136 Activation of the pregnane X receptor (PXR) reduces the risk of early allograft dysfunction following liver transplantation

<h3>Introduction</h3> There has been increasing interest in the pregnane X receptor (PXR) in recent years as a promising drug target for the treatment of inflammatory liver disease. Our group has previously demonstrated that activation of the PXR reduces oxidative stress and fibrosis in a rat model of liver ischaemia-reperfusion injury. The aim of this study was to investigate the effect of PXR activation on early graft function in clinical liver transplantation. <h3>Method</h3> Data was collected retrospectively for all patients receiving liver transplants in a major transplant centre in the UK over the past three years. Patients were divided into high and low PXR activation groups based on the potency and number of PXR-activating drugs administered over the first week of transplantation. Early allograft dysfunction (EAD) was measured using a validated scoring system and was compared between the two groups in addition to graft and patient survival. <h3>Results</h3> Eighty three patients were considered eligible for inclusion in this study (n = 43 and 40 in the low and high PXR activation groups respectively). The incidence of EAD was significantly higher in the low PXR activation group (30.2% vs. 10% in the high PXR activation group; P &lt; 0.05). No significant differences in graft or patient survival were demonstrated in this small cohort. <h3>Conclusion</h3> Activation of the PXR resulted in a reduction in EAD following liver transplantation in the clinical setting; consistent with our previous results in the animal model. Our findings have important implications for the potential reduction of graft loss following DCD liver transplantation. <h3>Disclosure of interest</h3> None Declared.

Gut microbiota and tacrolimus dosing in kidney transplantation.

Tacrolimus dosing to establish therapeutic levels in recipients of organ transplants is a challenging task because of much interpatient and intrapatient variability in drug absorption, metabolism, and disposition. In view of the reported impact of gut microbial species on drug metabolism, we investigated the relationship between the gut microbiota and tacrolimus dosing requirements in this pilot study of adult kidney transplant recipients. Serial fecal specimens were collected during the first month of transplantation from 19 kidney transplant recipients who either required a 50% increase from initial tacrolimus dosing during the first month of transplantation (Dose Escalation Group, n=5) or did not require such an increase (Dose Stable Group, n=14). We characterized bacterial composition in the fecal specimens by deep sequencing of the PCR amplified 16S rRNA V4-V5 region and we investigated the hypothesis that gut microbial composition is associated with tacrolimus dosing requirements. Initial tacrolimus dosing was similar in the Dose Escalation Group and in the Stable Group (4.2±1.1 mg/day vs. 3.8±0.8 mg/day, respectively, P=0.61, two-way between-group ANOVA using contrasts) but became higher in the Dose Escalation Group than in the Dose Stable Group by the end of the first transplantation month (9.6±2.4 mg/day vs. 3.3±1.5 mg/day, respectively, P<0.001). Our systematic characterization of the gut microbial composition identified that fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was 11.8% in the Dose Escalation Group and 0.8% in the Dose Stable Group (P=0.002, Wilcoxon Rank Sum test, P<0.05 after Benjamini-Hochberg correction for multiple hypotheses). Fecal Faecalibacterium prausnitzii abundance in the first week of transplantation was positively correlated with future tacrolimus dosing at 1 month (R=0.57, P=0.01) and had a coefficient±standard error of 1.0±0.6 (P=0.08) after multivariable linear regression. Our novel observations may help further explain inter-individual differences in tacrolimus dosing to achieve therapeutic levels.

P043 : ELEVATED EXPRESSION OF AIF-1 AND IL-18 AT EARLY KIDNEY TRANSPLANTATION MAY PREDICT ALLOGRAFT DYSFUNCTION BUT NOT THE DGF. NOVEL MARKERS OF PODOCYTES

Background We have recently reported cytokine gene profile in kidney allograft recipients during the first week of transplantation. The mRNA transcripts of AIF-1 and IL-18 were enhanced in patient’s blood and particularly podocytes in kidney biopsy samples with rejection episodes. Our aim was to explore the significance of these markers in early kidney dysfunction vs. rejection episodes. We hypothesized that these markers may help to identify patients at high risk of developing DGF or allograft rejection after transplantation. Methods A total of 390 patients who received kidney transplant between 2007 and 2011 at University of Mississippi Medical Center were investigated. Clinical data were stratified, including DGF, stable graft function (SGF), and rejection episodes (RE), which were analyzed on the basis of cellular or antibody mediated rejection. The RE time points were: 36 months. Three blood samples from each patient at different time intervals were tested, using a q-RT-PCR and designated gene primers for inflammatory markers. Results In a global analysis, rejection episode rate was 16.92% (66/390). Separating the data on the basis of rejection time points we observed the following rates: 5.6% (22/66) for rejection episodes within 36 months. The DGF was observed in 13.8%, SGF in 83% of patients after transplantation and 27 (7%) recipients returned to dialysis. IL-18 expression was significantly increased in patients who experienced DGF comparing the samples from pre-transplantation vs. day 3 and 6 post transplantation. AIF-1 was increased but not statistically significant. Both IL-18 and AIF-1 were significantly elevated during the first week of transplantation in patients who later experienced graft loss ( p p Conclusion The mRNA profiles of inflammatory markers observed in this study appeared to be predictive of allograft status and outcome. However, may not be useful to identify patients at high risk of delayed graft function.

Glutathione S-Transferase Iso-Enzymes in Perfusate From Pumped Kidneys Are Associated With Delayed Graft Function

Accurate and reliable assessment tools are needed in transplantation. The objective of this prospective, multi-center study was to determine the associations of the alpha and pi iso-enzymes of glutathione S-transferase (GST), measured from perfusate solution at the start and end (base and post) of kidney allograft machine perfusion, with subsequent delayed graft function (DGF). We also compared GST iso-enzyme perfusate levels from discarded versus transplanted kidneys. A total of 428 kidneys were linked to outcomes as recorded by the United Network of Organ Sharing. DGF, defined as any dialysis in the first week of transplant, occurred in 141 recipients (32%). Alpha- and pi-GST levels significantly increased during machine perfusion. The adjusted relative risks (95% confidence interval) of DGF with each log-unit increase in base and post pi-GST were 1.14 (1.0-1.3) and 1.36 (1.1-1.8), respectively. Alpha-GST was not independently associated with DGF. There were no significant differences in GST values between discarded and transplanted kidneys, though renal resistance was significantly higher in discarded kidneys. We found pi-GST at the end of machine perfusion to be independently associated with DGF. Further studies should elucidate the utility of GST for identifying injured kidneys with regard to organ allocation, discard and recipient management decisions.

Use of Breast Implants to Fill Postinfarct Pneumonectomy Cavity in Cases of Bilateral Lung Transplantation

Infarction of the lung graft following lung transplantation (LTx) needing graft pneumonectomy and retransplantation is rare and carries a poor prognosis. It is important to maintain the volume of hemithorax after pneumonectomy until retransplantation.A young woman who received bilateral LTx for idiopathic pulmonary hypertension underwent left graft pneumonectomy owing to infarction related to obstruction of pulmonary veins. After pneumonectomy, left hemithorax was filled with silicon breast implants (1 × 500 mL and 2 × 250 mL). A Taurolidine drip was started into the left chest cavity and was maintained 24 h/d for 5 d to avoid infection of breast implants (Fig 1). After 9 weeks when suitable single lung donor became available, the left chest was opened, the breast implants were removed, and a new organ was transplanted. The patient made a rapid recovery after retransplantation and was discharged home after 4 weeks. In another woman in her mid 40s with bilateral LTx for pulmonary fibrosis, two 500-mL implants were placed following left graft pneumonectomy for pulmonary artery obstruction (Fig 2). Gas exchange from a single lung was inadequate and required extracorporeal life support, from which she could not be weaned and died after 1 month from refractory liver failure.Fig 2View Large Image Figure ViewerDownload (PPT)In these cases, graft pneumonectomy was performed within the first week of transplantation. The plan was to offer retransplantation as the patients' condition stabilized and suitable donor organs became available. It was important to preserve the space in hemithorax, because mediastinal shift, diaphragmatic elevation, and rib crowding seen after pneumonectomy would have obliterated it. The use of breast implants for filling the hemithorax preserved the space so that the retransplantation with an appropriately sized organ would be possible. Breast implants also had a tamponade effect and prevented bleeding from the hilum and chest wall after pneumonectomy. The risk of herniation of the heart through the pericardial rent made for hilar dissection of the native lung was also prevented by breast implants. Infarction of the lung graft following lung transplantation (LTx) needing graft pneumonectomy and retransplantation is rare and carries a poor prognosis. It is important to maintain the volume of hemithorax after pneumonectomy until retransplantation. A young woman who received bilateral LTx for idiopathic pulmonary hypertension underwent left graft pneumonectomy owing to infarction related to obstruction of pulmonary veins. After pneumonectomy, left hemithorax was filled with silicon breast implants (1 × 500 mL and 2 × 250 mL). A Taurolidine drip was started into the left chest cavity and was maintained 24 h/d for 5 d to avoid infection of breast implants (Fig 1). After 9 weeks when suitable single lung donor became available, the left chest was opened, the breast implants were removed, and a new organ was transplanted. The patient made a rapid recovery after retransplantation and was discharged home after 4 weeks. In another woman in her mid 40s with bilateral LTx for pulmonary fibrosis, two 500-mL implants were placed following left graft pneumonectomy for pulmonary artery obstruction (Fig 2). Gas exchange from a single lung was inadequate and required extracorporeal life support, from which she could not be weaned and died after 1 month from refractory liver failure. In these cases, graft pneumonectomy was performed within the first week of transplantation. The plan was to offer retransplantation as the patients' condition stabilized and suitable donor organs became available. It was important to preserve the space in hemithorax, because mediastinal shift, diaphragmatic elevation, and rib crowding seen after pneumonectomy would have obliterated it. The use of breast implants for filling the hemithorax preserved the space so that the retransplantation with an appropriately sized organ would be possible. Breast implants also had a tamponade effect and prevented bleeding from the hilum and chest wall after pneumonectomy. The risk of herniation of the heart through the pericardial rent made for hilar dissection of the native lung was also prevented by breast implants.