Preserve Graft Function Research Articles

The Efficacy and Safety of Belatacept in Heart Transplant Recipients

<h3>Purpose</h3> Belatacept (BTC) is a high-affinity CTLA4-Ig variant indicated for prophylaxis of graft rejection in adults receiving a kidney transplant. Data on the utilization of BTC therapy in heart transplant (HT) recipients are scarce. The aim of this study was to describe the use of BTC as a treatment option in selected HT pts <h3>Methods</h3> We conducted a retrospective analysis of all pts who underwent HT between 1/2017 and 4/2020 and received BTC. Baseline characteristics, rejection and infection history were collected. Key laboratory finding and graft function were compared at 6 and 12 months. <h3>Results</h3> Out of 776 patients who received a HT during the study period, 21 pts were treated with BTC and were included in this analysis. Mean age at time of HT was 53 ±12 years, 38% were female. BTC was initiated a median of 22.6 months IQR [22.6-66.8] after HT. The most common indication for BTC was elevated DSA (61.9% of patients) followed by renal protection (23.8%). Only 1 patient experienced grade 2R rejection in the 12 months following initiation of BTC and 1 additional pts had pAMR 1H. Graft function was unchanged at 6 and 12 months. Serum creatinine improved in 76.2% of the patients from a median of 1.58 IQR [1.0-2.1] at baseline to 1.45 IQR [1.1-1.9] at 12 months (p=0.054). At 6 and 12 months following BTC therapy, no significant differences were found in hemoglobin (11.3 vs 11.1 g/dl) or white blood cell count (5.9 vs 6.1 × 10³uL). 33.3% experienced infection (71.4% viral infection, 28.5% bacterial 14.2% fungal). 33.3% of the patients required temporary discontinuation of treatment due to the side effects and 4 patients were switched back to CNI (19%). <h3>Conclusion</h3> BTC therapy was used predominantly for management of elevated DSA or for renal protection. BTC therapy resulted in improved kidney function and was associated with a low rejection rate and preserved graft function. Infections were common during BTC therapy and BCT was discontinued in 19% of patients due to side effects. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.

Benign course of residual inflammation at end of treatment of liver transplant recipients after sofosbuvir based therapy.

BACKGROUNDPersistent inflammation on histology after successful hepatitis C (HCV) treatment has been reported. However, data regarding the long-term impact in liver transplant recipients is limited, particularly after using direct-acting antiviral (DAA) therapies. AIMTo evaluate the impact of successful treatment with DAAs on histological changes and occult HCV and to describe the clinical course of residual inflammation in liver transplant recipients.METHODSWe conducted a case series of 13 chronic HCV infected liver transplant recipients successfully treated with DAAs between December 2013 and May 2014. All patients were treated for 24 wk and had non-detectable serum HCV RNA by the time of biopsy. Only patients with at least one liver biopsy at or after treatment were included. We examined liver biopsies for evidence of residual inflammation and the presence of intrahepatic HCV RNA.RESULTSPersistent inflammation was seen in 12/13 patients on end of treatment biopsy. Inflammation was still seen in the available five follow-up biopsies (range 38-48 wk after the end of treatment). Intrahepatic HCV RNA was undetectable in all biopsies. All patients had preserved graft function for a mean follow-up of 2.5 years, except one that developed chronic rejection. CONCLUSIONAfter successful HCV treatment with DAAs, liver transplant recipients may have persistent inflammation on biopsy without evidence of intracellular RNA. The clinical outcome remained favorable in most patients. Further studies with a larger number and longer follow-up are needed to establish the implication of this finding on long-term graft function.

Post-transplant Lymphoproliferative Disorder Following Cardiac Transplantation.

Post-transplant lymphoproliferative disorder (PTLD) is a spectrum of lymphoid conditions frequently associated with the Epstein Barr Virus (EBV) and the use of potent immunosuppressive drugs after solid organ transplantation. PTLD remains a major cause of long-term morbidity and mortality following heart transplantation (HT). Epstein-Barr virus (EBV) is a key pathogenic driver in many PTLD cases. In the majority of PTLD cases, the proliferating immune cell is the B-cell, and the impaired T-cell immune surveillance against infected B cells in immunosuppressed transplant patients plays a key role in the pathogenesis of EBV-positive PTLD. Preventive screening strategies have been attempted for PTLD including limiting patient exposure to aggressive immunosuppressive regimens by tailoring or minimizing immunosuppression while preserving graft function, anti-viral prophylaxis, routine EBV monitoring, and avoidance of EBV seromismatch. Our group has also demonstrated that conversion from calcineurin inhibitor to the mammalian target of rapamycin (mTOR) inhibitor, sirolimus, as a primary immunosuppression was associated with a decreased risk of PTLD following HT. The main therapeutic measures consist of immunosuppression reduction, treatment with rituximab and use of immunochemotherapy regimens. The purpose of this article is to review the potential mechanisms underlying PTLD pathogenesis, discuss recent advances, and review potential therapeutic targets to decrease the burden of PTLD after HT.

Long-Term Management of Post-Transplant Ureteral Stricture with Surgical Reconstruction: A Case Series and Literature Review

Introduction: Ureteral stricture is the most common complication after kidney transplant and is largely responsible for graft dysfunction. Surgical intervention is the definitive treatment if conservative management with stenting and percutaneous nephrostomy tube placement fails and has been shown to have comparable long-term survival rates and limited post-operative complications. Methods: This is a single-center retrospective study following seven patients who received a kidney or a kidney and pancreas transplant between August 2012 and January 2021. These patients underwent surgical ureteral reconstruction after failed conservative management of a ureteral stricture. The reconstruction procedures performed were native ureter to transplanted kidney ureteropyelostomy, native bladder to transplanted renal pelvis vesicopyelostomy, non-transecting side-to-side ureteroneocystostomy, and a Boari flap creation. Data collected from electronic medical records included recipient age, gender, delayed post-transplant complications, ureteral reconstruction technique, and post-reconstruction outcomes. Renal ultrasound (RUS), renogram, nephrostogram, serum creatinine (Cr), and graft biopsy were used to assess for severity of hydronephrosis, ureteral stricture, and graft dysfunction. Serum Cr and RUS were used to assess renal function after the ureteral reconstruction. Results: Six out of seven cases resulted in reduced or resolved hydronephrosis and preserved graft function without future nephrostomy or ureteral stenting. One case required immediate revision due to persistent obstruction, and this patient had concomitant rejection leading to intrarenal stricture requiring ureterocalycostomy. Conclusions: Formal ureteral reconstruction is the definitive treatment for many cases of ureteral strictures after transplant. The surgical technique chosen for these procedures must consider the physical and functional state of the bladder, ureter, and kidney. Our series outlines multiple surgical approaches that should be considered early in the management of post-transplant ureteral strictures to limit graft dysfunction.

Perspectives of solid organ transplant recipients on medicine-taking: Systematic review of qualitative studies

Medicine-taking among transplant recipients is a complex and ubiquitous task with significant impacts on outcomes. This study aimed to describe the perspectives and experiences of medicine-taking in adult solid organ transplant recipients. Electronic databases were searched to July 2020, and thematic synthesis was used to analyze the data. From 119 studies (n=2901), we identified six themes: threats to identity and ambitions (impaired self-image, restricting goals and roles, loss of financial independence); navigating through uncertainty and distrust (lacking tangible/perceptible benefits, unprepared for side effects, isolation in decision-making); alleviating treatment burdens (establishing and mastering routines, counteracting side effects, preparing for the unexpected); gaining and seeking confidence (clarity with knowledge, reassurance through collective experiences, focusing on the future outlook); recalibrating to a new normal posttransplant (adjusting to ongoing dependence on medications, in both states of illness and health, unfulfilled expectations); and preserving graft survival (maintaining the ability to participate in life, avoiding rejection, enacting a social responsibility of giving back). Transplant recipients take medications to preserve graft function, but dependence on medications jeopardizes their sense of normality. Interventions supporting the adaptation to medicine-taking and addressing treatment burdens may improve patient satisfaction and capacities to take medications for improved outcomes.

POS-701 OVER TEN-YEARS KIDNEY GRAFT SURVIVAL DETERMINANTS : A SINGLE CENTER EXPERIENCE

Renal transplantation is the treatment of choice for patients with end-stage kidney disease, offering cost, quality of life, and survival benefits over the alternative of dialysis. Over the past few decades surgical and medical advances have led to continuous improvement in short term graft survival, but this progress has not been accompanied by similar improvements in long-term graft survival and kidney transplant recipients continue to experience late allograft failure. The aim of this study was to estimate long-term survival rate of kidney transplantation and to detect associated prognostic factors. This is a retrospective study included adults who underwent kidney transplantation between 1995 and 2008 in the nephrology department of the Fattouma Bourguiba Hospital in Monastir (Tunisia). They were followed until 31 December 2018.Therefore, this cohort was followed for at least 10 years. Data were collected from patients’ medical records using a checklist. We compared the demographic, clinical, immunological, and laboratory profile of patients who had functional grafts ≥ 10 years after kidney transplantation to those whose transplants survived <10 years. Kaplan-Meier curve, log-rank test was used to compare survival curves and Cox proportional hazard model were used to multivariate analysis. The study cohort included 59 patients with a mean age of 30,83±10,14 years with M:F ratio of 1.68. The mean graft survival was 11.22±4,14 years in the overall cohort. The graft survival rates at 1 ,3, 5, 7 and 10 years were 98,3%,93,2%,89,8%,81,4%and 59,3% respectively. We identified 45 (76 ,3%) patients with a functional graft for 10 or more years after transplantation and 18.6% for 15 or more. In the univariate analyses factors statistically associated to long survival (≥ 10-year) were: recipient age below 35 years (P = 0.016), ABO-identical matching (P = 0.02), higher 3 month (P = 0.01) , one-year (P = 0.01), 5 years (P = 0.02) estimated glomerular filtration rate and no CMV infection after transplantation (P = 0.01). Our experience in renal transplantation survival rates indicate a success rate comparable to those noted in other reports. The renal function at 1-year after transplantation is important for the 10-year survival of kidney transplants. Accordingly, efforts should be targeted to preserving graft function in the first year after kidney transplantation.

Comparison of De Novo Donor Specific and Non-Specific Antibodies on the Outcome after Heart Transplantation

Purpose Studies have shown that donor specific antibodies (DSA) have great impact on the clinical course and overall survival of patients after heart transplantation (HTx). De-novo non-DSA (NSA) were associated with graft loss after kidney transplantation, but it remains unclear to what extent NSA play a role in rejection, graft function and overall mortality after HTx. The aim of this study was to analyze and compare the outcome of patients with DSA and NSA after HTx. Methods Surveillance endomyocardial biopsies (EMB) were taken after 1, 3, 6 months and yearly for 5 years after HTX, and cardiac allograft vasculopathy (CAV) was evaluated via coronary angiography. Serum HLA-class I and II antibodies were collected for analysis of donor specifity twice yearly. The antibody mean fluorescence intensity (MFI) cut-off values were set at >1000. Study data was collected retrospectively from internal medical records. End points of the study were death of any cause, primary graft failure (PGF), biopsy proven acute cellular rejection (BPACR) ≥2R according to ISHLT, antibody mediated rejection (AMR) and CAV. Complete data was obtained only from patients with a survival of 12 months or greater. Results 69 patients with a follow-up time of min. 18 months to max. 6 years after HTx were divided into two groups (G1: no DSA or NSA present, n=41, G2: DSA and / or NSA present, n=27). G2 was further divided into two subgroups, patients with both DSA + NSA (n=9) and only NSA(n=26) status.All-cause mortality was n=21 (30.9%), with significant difference amongst the groups (G1: n=17 (41.5%), G2: n=4(18.4%)). This trend was also seen amongst cardiovascular mortality (G1: n=7 (17.1%), G2: n=0). No statistically significant difference was seen regarding CAV (G1: n=3 (7.3%), G2: n=2 (7.4%)), BPACR (G1: n=19 (27.9%) or G2: n=9 (22%)). Surprisingly, AMR was seen in patients in G1 n=3 (4.4%), but not in G2 (n=0), however, without statistically relevant difference. Conclusion Our study shows that DSA and NSA had no negative impact on the outcome up to 6 years after HTx. This might be due to a closer monitoring of the patients after detection of DSA and NSA, and, consequently, an adequate and early adjustment of immunosuppressive therapy including specific DSA treatments to preserve graft function.

Intravenous iron supplement for iron deficiency in cardiac transplant recipients (IronIC): A randomized clinical trial

Heart transplant recipients have reduced exercise capacity despite preserved graft function. The IronIC trial was designed to test the hypothesis that intravenous iron therapy would improve peak oxygen consumption in these patients. This randomized, placebo-controlled, double-blind trial was performed at our national center for heart transplantation. One hundred and 2 heart transplant recipients with a serum ferritin <100 µg/liter or 100 to 300 µg/liter, in combination with transferrin saturation of <20%, and hemoglobin level >100 g/liter were enrolled ≥1 year after transplantation. A cardiopulmonary exercise test was performed before administration of the study drug and at 6 months follow-up. The primary endpoint was peak oxygen consumption. Key secondary outcomes included iron status, handgrip strength, quality of life, and safety. Fifty-two patients were randomized to receive ferric derisomaltose 20 mg/kg, and 50 to placebo. The between-group difference in baseline-adjusted peak oxygen consumption was 0.3 ml/kg/min (95% confidence interval -0.9 to 1.4, p = 0.66). In patients with a baseline ferritin <30 µg/liter, peak oxygen consumption was significantly higher in the ferric derisomaltose arm. At 6 months, iron stores were restored in 86% of the patients receiving ferric derisomaltose vs 20% in patients receiving placebo (p < 0.001). Quality of life was significantly better in patients receiving ferric derisomaltose. Twenty-seven adverse events occurred in the intravenous iron group vs 30 in the placebo group (p = 0.39). Intravenous iron treatment did not improve peak oxygen consumption in heart transplant recipients with ferritin <100 µg/liter or 100 to 300 µg/liter in combination with transferrin saturation <20%. http//www.clinicaltrials.gov identifier NCT03662789.

USO DE ESTATINAS NO CONTROLE DA HIPERLIPIDEMIA PÓS-TRANSPLANTE RENAL: FATORES ASSOCIADOS E POSSÍVEIS BENEFÍCIOS EM UMA REVISÃO DO TIPO NARRATIVA

Preservation of graft function is the major concern in the follow-up of kidney transplant recipients. In contrast, those patients are subjected to cardiovascular disease, hypertension, dyslipidemia, diabetes mellitus, adverse effects of immunosuppressant drugs with altered lipoprotein levels and other metabolic disorders, which can contribute to graft loss and increased morbidity and mortality. Lipid lowering therapy with statins can offer protection to the renal graft endothelium, with consequently decreased rejection rates and improved quality of life. The present study aimed to approach the use of statins as lipid-lowering therapy in kidney transplant recipients, through a narrative review of the literature. A search was conducted on the following platforms: Pubmed, Scielo, LILACS, Cochrane Library and MedRxiv, which was followed by explanatory reading. Eleven scientific articles with the descriptors: ‘Kidney Transplantation’, ‘Hydroxymethylglutaryl-CoA Reductases Inhibitors’ and ‘Hypercholesterolemia’ were included. Of those studies, 45.6% (5) discuss the benefits of using statins to control lipid rates, 36.4% (4) describe the risks and benefits of using statins for damage progression, and 18% (2) report the effectiveness of statins associated with other drugs. The use of Hydroxymethylglutaryl-CoA Reductase Inhibitors (statins) has clinical relevance in kidney transplant recipients, with the main purpose to lowering the lipid levels, thus increasing the safety of treatment and promoting benefits for kidney transplant recipients.

Positively Double Jeopardy - Dual Organ Transplantation in an HIV+ Patient

Intro : Solid organ transplantation (SOT) is uncommon in persons living with HIV infection (PLWHIV), as historically, HIV infection was a contraindication to transplantation. However, advancements in antiretroviral therapy (ART) and immunosuppression has led to successful organ transplantation, including heart, in PLWHIV. Here, we present a case of dual-organ transplant in a PLWHIV. Case Report : A 46 yo African American man with Stage D heart failure due to dilated cardiomyopathy, end-stage renal disease (ESRD) on peritoneal dialysis (PD), and longstanding HIV infection (CD4 726 cells/µl, HIV RNA less than 20 copies/mL) presented in cardiogenic shock. On hospital day 5, an axillary intra-aortic balloon pump (IABP) was placed, and the patient was upgraded to a status 2 on the UNOS waitlist for heart-kidney transplantation. On hospital day 33, he received a heart transplant, followed the next day with a deceased donor renal transplant from the same donor. He underwent induction with basiliximab 20 mg, on POD#0 and #4, followed by immunosuppression with mycophenolate mofetil 1g BID, tacrolimus 3mg BID, and prednisone 10mg BID. The pre-transplant ART with dolutegravir/rilpivirine was resumed and he was initiated on standard anti-infective prophylaxis with valganciclovir, atovaquone, and clotrimazole. Hospital course was complicated by hospital-acquired pneumonia and delayed kidney graft function with acute tubular necrosis, initially requiring hemodialysis. There was no evidence of antibody mediated or acute cellular rejection on endomyocardial biopsies. Two months after transplant, the patient was found to have BK viremia, initiated on cidofovir. Four months post-transplant, he was no longer requiring dialysis, had preserved graft function on echocardiogram, and transitioned from atovaquone to sulfamethoxazole-trimethoprim for a lifelong course. Most recent labs notable for sCr 1.66 mg/dL, eGFR 54 mL/min/1.73m2, CD4 890 cells/µl, HIV RNA less than 20 copies/mL, BK virus quantitative PCR 23,875 copies/mL. His current immunosuppressive regimen includes mycophenolate mofetil 250mg BID and tacrolimus 2mg BID. Summary Patients with advanced heart failure who are concomitantly HIV+ are a unique and growing population. Multi-organ transplantation involving heart and kidney in this patient population has not been reported in the literature. As demonstrated in this case, with special considerations to patient selection, immunosuppression, and anti-infective regimens, and collaboration of a multidisciplinary team of heart and kidney transplant physicians and surgeons, along with infectious disease specialists, a successful multi-organ heart-kidney transplant in PLWHIV is feasible with excellent outcomes early after transplant.

Böbrek Nakli Sonrası Önemli Bir Komplikasyon: Transplant Renal Arter Stenozu

Renal transplantation is a preferred treatment option because of its low long-term mortality and increased quality of life. However, complications after transplantation affect graft and patient survival. Transplant Renal Artery Stenosis (TRAS) is the most common vascular complication following renal transplantation affecting 1-23% of patients. Although it usually causes refractory hypertension, it can also cause graft loss. Although Peripheral Angiography (Digital subtraction angiography) is the gold standard for the diagnosis of TRAS, Doppler USG has become a primary imaging method because it is portable, inexpensive and noninvasive. There are surgical and endoluminal options in the treatment. In this report, a 16-year-old girl who had renal artery stenosis at the 4th month after renal transplantation and underwent percutaneous transluminal balloon angioplasty was reported. She is now in her second year of transplantation without any need for antihypertensive treatment and with preserved graft function.

Alloimmunity in pancreas transplantation.

Despite significant improvement in pancreas allograft survival, rejection continues to be a major clinical problem. This review will focus on emerging literature related to the impact of pretransplant and de-novo DSA (dnDSA) in pancreas transplant recipients, and the diagnosis and treatment of T-cell-medicated rejection (TCMR) and antibody-mediated rejection (ABMR) in this complex group of patients. Recent data suggest that pretransplant DSA and the emergence of dnDSA in pancreas transplant recipients are both associated with increased risk of ABMR. The pancreas allograft biopsy is essential for the specific diagnosis of TCMR and/or ABMR, distinguish rejection from other causes of graft dysfunction, and to guide-targeted therapy. This distinction is important especially in the setting of solitary pancreas transplants but also in simultaneous pancreas-kidney transplants where solid evidence has now emerged demonstrating discordant biopsy findings. Treatment of rejection in a functioning pancreas can prolong allograft survival. The accurate and timely diagnosis of active alloimmune destruction in pancreas transplant recipients is paramount to preserving graft function in the long term. This review will discuss new, rapidly evolving information that is valuable for the physician caring for these patients to achieve optimal immunological outcomes.

Intra-Arterial Hemodynamics to Guide the Percutaneous Treatment of a Difficult-to-Engage Transplant Renal Artery Stenosis

Transplant renal artery stenosis (TRAS) is the most frequent vascular complication after renal transplantation. TRAS is associated with resistant hypertension and allograft dysfunction, early diagnosis and either endovascular or surgical treatment is crucial to preserve graft function. Noninvasive imaging can usually detect the underlying stenosis. In this report we present a novel technique for successful angioplasty and stent deployment in a difficult-to-engage transplant-renal artery.

How Early Postoperative Urinary Tract Infections Affect Renal Graft Function at 1-Year Follow-up

BackgroundUrinary tract infection (UTI) occurs in 21% of kidney recipients within the first 3 months after transplantation (KTx). It is associated with impaired graft function. Ureteral stent placement increases the occurrence of UTIs.The aim of this study was to assess the correlation between double-J placement, UTI incidence, and graft function. Material and MethodsWe conducted an observational study in 753 patients transplanted between 2010 and 2017 in compliance with the Helsinki Congress and the Istanbul Declaration. Recipients with preserved graft function at the 1-year follow-up were included.Medical records were searched for intraoperative double-J placement, UTI incidence, and estimated glomerular filtration rate (eGFR) on the 30th and 360th days post-transplant.Pretransplant hypothetical estimated GFR (heGFR) of each donor was calculated from donors’ age and physiological age-dependent loss of functional nephrons.Spearman’s correlation and linear regression analyses were applied. P < .05 was considered significant. ResultsUTIs occurred in 239 (31.8%) patients. On the 30th day after KTx, eGFR was significantly lower in the UTI group (median, 39.5 vs 43.2; P < .01). A similar pattern was seen 1 year after KTx (47.5 vs 54.2; P < .01).Urinary stents were placed in 213 (28.3%) patients. UTIs occurred in 92 (43.2%) of them and in 147 (27.2%) of nonstented patients (odds ratio: 2; 95% confidence interval [CI], 1.5-2.8; P < .01).Median donor heGFR was 105.8 mL/min/1.73 m2, whereas median donor Modification of Diet in Renal Disease (MDRD) GFR was 64.2 mL/min/1.73 m2. A moderate correlation between age-adjusted heGFR and 1-year transplant function (r = .47) was noted. ConclusionsUTIs in the early post-transplant period decreased 1-year eGFR by 4 to 5 mL/min/1.73 m2. UTIs occurred twice as often when a urinary stent was placed.

Intravenous Iron Supplement for Iron Deficiency in Cardiac Transplant Recipients (IronIC) - A Randomized, Double Blind, Controlled Trial

Heart transplant recipients have reduced exercise capacity despite preserved graft function. Numerous mechanisms may contribute to this impaired exercise tolerance, one of which may be iron deficiency (ID). Among our heart transplant survivors, 48 % have ID. The IronIC trial (NCT03662789) was designed to test the hypothesis that intravenous (i.v.) iron therapy will improve exercise capacity assessed by peak oxygen consumption. 102 stable, cardiac transplant recipients with ID, defined as serum ferritin <100 µg/l, or ferritin between 100 and 300 µg/l in combination with transferrin saturation <20 %, have been randomized in a 1:1 manner to treatment with intravenous iron isomaltoside, 20 mg/kg, or NaCl. Care was taken to blind patients and personnel to the color of the infusate. All participants provided written, informed consent. Exclusion criteria included hemoglobin <100 g/l, red blood cell disorders, end-stage kidney failure, intolerance to iron isomaltoside, and ongoing infections or rejections. Prior to the intervention, all patients underwent a treadmill test to measure peak oxygen consumption. Muscle strength by a hand grip test, cognitive function, and self-reported quality of life were also measured. All tests are repeated at follow-up 6 months after intervention. The trial is powered to detect a 1.5 ml/kg/min between-group difference in the change in peak oxygen consumption. Last patient is scheduled for follow-up February 2020. The primary objective is to assess baseline-adjusted peak oxygen consumption, six months after one single dose of iron isomaltoside. Secondary objectives are to assess the impact of treatment on iron stores, muscle strength, cognitive function, quality of life, safety and tolerability. This study will give insight to whether heart transplant recipients with ID can benefit from intravenous iron supplement. Results will be ready for presentation at the 2020 ISHLT conference.

Tacrolimus-Associated Psychotic Disorder: A Report of 2 Cases

Psychotic disorders are a group of psychiatric disorders characterized by the presence of delusions, hallucinations, bizarre behavior, and disorganized speech. There are several possible causes for the occurrence of psychotic disorders in patients who underwent solid organ transplant, including pre-existing mental illness, electrolyte disturbances, infections of the central nervous system, and adverse reaction to drugs. Calcineurin inhibitors are a class of immunosuppressive drugs, such as tacrolimus and cyclosporine, that are currently considered the mainstay in the immunosuppressive drug regimen of patients who underwent solid organ transplant. Neurotoxicity is one of the adverse reactions associated with the use of calcineurin inhibitors, ranging from upper limb tremors to psychotic disorders and seizures. We report the cases of 2 liver transplant recipients who developed severe psychotic disorder 1 month after the procedure. After an extensive investigation for other possible triggers of psychiatric disease, the use of tacrolimus was considered to be the most likely cause for the acute psychotic disorder. In less than 24 hours after suspension of that drug, all symptoms disappeared in both patients, making a causal relationship with tacrolimus even more likely. The patients were then given cyclosporine, another drug from the same class, allowing for adequate immunosuppression and preserved graft function, with no further psychiatric symptoms. This report confirms that a 24-hour trial of tacrolimus suspension can be safe and effective in the diagnosis of drug-related psychotic disorders in patients who underwent liver transplant. This article is compliant with the Helsinki Congress and the Istanbul Declaration.

AAV-mediated TIMP-1 overexpression in aortic tissue reduces the severity of allograft vasculopathy in mice

Allograft vasculopathy (AV) is the primary limiting factor for long-term graft survival. An increased activity of matrix metalloproteinases (MMPs) contributes to neointima formation in AV and represents a potential therapeutic target. Adeno-associated virus (AAV)-mediated gene therapy comprises a potentially benign vector model for the long-term expression of MMP antagonists. Aortic allografts from DBA/2 mice were incubated with control buffer, AAV-enhanced green fluorescence protein (EGFP), or tissue inhibitor of metalloproteinases 1 (TIMP-1)-loaded AAV (AAV-TIMP-1) and transplanted into the infrarenal aorta of C57BL/6 mice. Cyclosporine A (10 mg/kg body weight) was administered daily. Explantation as well as histomorphometric and immunohistochemical evaluation was performed after 30 days. Matrix metalloproteinase (MMP) activity was visualized by gelatin in situ zymography. Intima-to-media area ratio and neointima formation were significantly reduced in the AAV-TIMP-1 treatment group compared with those in the control group (by 40%; p < 0.001) and the AAV-EGFP group (by 38.2%; p < 0.001). TIMP-1 overexpression positively affected several pathomechanisms for the development of AV both in vitro and in vivo as compared to that in the control groups: endothelium integrity was preserved as shown by zona occludens 1 and occludin staining; MMP9 expression and activity were significantly reduced (p = 0.01); and smooth muscle cell migration was significantly reduced as smooth muscle actin positive cells predominantly remained in the aortic media in the treatment group (p = 0.001). Moreover, macrophage infiltration was markedly reduced by 49% in the AAV-TIMP-1 group (p < 0.001). Immediate post-harvesting allograft incubation with AAV-TIMP-1 reduces neointima formation and macrophage infiltration, constituting a possible adjunct therapeutic strategy to preserve graft function after transplantation.

Imaging of Transplant Emergencies

Abstract Abdominal organ transplants most commonly involve the liver, kidney, and pancreas, and are considered the definitive treatment for end-stage organ failure. A number of complications may arise that can threaten transplant organ function. These complications can involve transplant organ parenchyma, vascular structures, and the different structures that are unique to each transplant organ. Although the complication rate is low, they can result in significant morbidity and need to be recognized in a timely manner by radiologists in order to preserve graft function and optimize patient outcomes. As the number of abdominal organ transplants increase and long-term survival rates continue to improve, radiologists can expect to encounter transplant patients in daily practice and should be familiar with the imaging appearance of transplant surgical anatomy and the spectrum of complications that can potentially affect these transplant organs.

Laparoscopic Sleeve Gastrectomy in a Morbidly Obese Kidney Recipient for Preserving Graft Function

The obesity epidemic involves the healthy population and transplant recipients equally. In renal transplantation, obesity is not only associated with a number of disorders exerting adverse effects on the transplanted organ, but with poorer graft function and peritransplant complications. Treating obesity in transplant patients can improve graft function and manage comorbidities that are associated with renal failure. As conservative weight loss programs shows disappointing results in these patients, bariatric surgery is the most effective and long term treatment for obesity

Intravenous Iron Supplement for Iron Deficiency in Cardiac Transplant Recipients (IronIC): Rationale and Design of a Randomized, Controlled Trial

Purpose Heart transplant recipients have reduced exercise capacity, despite preserved graft function. Numerous mechanisms may contribute to this impaired exercise tolerance, one of which may be iron deficiency (ID). Among our heart transplant survivors, 48 % have ID defined as serum ferritin Methods The IronIC trial is a randomized, controlled trial designed to test the efficacy and safety of a single bolus of iron isomaltoside in adult, stable heart transplant recipients with ID. We aim to randomize 100 patients in a 1:1 fashion to receive i.v. iron isomaltoside 20 mg/ kg body weight, or NaCl, in a double-blind manner. The trial is powered to detect a 1.5 ml/kg/min between-group difference in the change in peak oxygen consumption. Secondary objectives are to assess the impact of treatment on iron stores, hand grip strength, body composition, cognitive function, quality of life, and safety and tolerability. All participants must provide written, informed consent. Exclusion criteria include hemoglobin Results All regulatory approvals have been obtained. Recruitment started April 2018 and is expected to end April 2019, with last follow-up October 2019. So far, there have been no serious adverse events. Demographics for the first 41 patients are presented in the Table. Conclusion The IronIC trial is an ongoing, randomized, controlled, double blind study designed to assess the efficacy and safety of a single, i.v. bolus of iron in heart transplant recipients with ID. We expect results to be available at the end of 2019.