Journal of Transplantation The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Liver Transplantation for Hepatocellular Carcinoma: A Single Center Resume Overlooking Four Decades of Experience Sun, 10 Jan 2016 09:48:22 +0000 Background. This is a single center oncological resume overlooking four decades of experience with liver transplantation (LT) for hepatocellular carcinoma (HCC). Methods. All 319 LT for HCC that were performed between 1975 and 2011 were included. Predictors for HCC recurrence (HCCR) and survival were identified by Cox regression, Kaplan-Meier analysis, Log Rank, and -tests where appropriate. Results. HCCR was the single strongest hazard for survival (). Hazards for HCCR were tumor staging beyond the histologic MILAN (), bilateral tumor spreading (), tumor grading beyond G2 (), and vascular infiltration of small or large vessels (, , resp.). Grading beyond G2 () as well as small and large vascular infiltrations (, , resp.) was associated with higher hazard ratios for long-term survival as compared to liver transplantation beyond histological MILAN (). Tumor dedifferentiation significantly correlated with vascular infiltration () and intrahepatic tumor spreading (). Conclusion. LT enables survival from HCC. HCC dedifferentiation is associated with vascular infiltration and intrahepatic tumor spreading and is a strong hazard for HCCR and survival. Pretransplant tumor staging should include grading by biopsy, because grading is a reliable and easily accessible predictor of HCCR and survival. Detection of dedifferentiation should speed up the allocation process. Nikos Emmanouilidis, Rickmer Peters, Bastian P. Ringe, Zeynep Güner, Wolf Ramackers, Hüseyin Bektas, Frank Lehner, Michael Manns, Jürgen Klempnauer, and Harald Schrem Copyright © 2016 Nikos Emmanouilidis et al. All rights reserved. Lung Transplantation in Patients with High Lung Allocation Scores in the US: Evidence for the Need to Evaluate Score Specific Outcomes Mon, 21 Dec 2015 13:54:04 +0000 Objective. The lung allocation score (LAS) resulted in a lung transplantation (LT) selection process guided by clinical acuity. We sought to evaluate the relationship between LAS and outcomes. Methods. We analyzed Scientific Registry of Transplant Recipient (SRTR) data pertaining to recipients between 2005 and 2012. We stratified them into quartiles based on LAS and compared survival and predictors of mortality. Results. We identified 10,304 consecutive patients, comprising 2,576 in each LAS quartile (quartile 1 (26.3–35.5), quartile 2 (35.6–39.3), quartile 3 (39.4–48.6), and quartile 4 (48.7–95.7)). Survival after 30 days (96.9% versus 96.8% versus 96.0% versus 94.8%), 90 days (94.6% versus 93.7% versus 93.3% versus 90.9%), 1 year (87.2% versus 85.0% versus 84.8% versus 80.9%), and 5 years (55.4% versus 54.5% versus 52.5% versus 48.8%) was higher in the lower groups. There was a significantly higher 5-year mortality in the highest LAS group (HR 1.13, , HR 1.17, , and HR 1.17, ) comparing quartiles 2, 3, and 4, respectively, to quartile 1. Conclusion. Overall, outcomes in recipients with higher LAS are worse than those in patients with lower LAS. These data should inform more individualized evidence-based discussion during pretransplant counseling. Jeremiah A. Hayanga, Alena Lira, Tedi Vlahu, Jingyan Yang, Jonathan K. Aboagye, Heather K. Hayanga, James D. Luketich, and Jonathan D’Cunha Copyright © 2015 Jeremiah A. Hayanga et al. All rights reserved. Risk Factors Associated with Increased Morbidity in Living Liver Donation Tue, 15 Dec 2015 14:25:59 +0000 Living donor liver donation (LDLD) is an alternative to cadaveric liver donation. We aimed at identifying risk factors and developing a score for prediction of postoperative complications (POCs) after LDLD in donors. This is a retrospective cohort study in 688 donors between June 1995 and February 2014 at Hospital Sírio-Libanês and A.C. Camargo Cancer Center, in São Paulo, Brazil. Primary outcome was POC graded ≥III according to the Clavien-Dindo classification. Left lateral segment (LLS), left lobe (LL), and right lobe resections (RL) were conducted in 492 (71.4%), 109 (15.8%), and 87 (12.6%) donors, respectively. In total, 43 (6.2%) developed POCs, which were more common after RL than LLS and LL (14/87 (16.1%) versus 23/492 (4.5%) and 6/109 (5.5%), resp., ). Multivariate analysis showed that RL resection (OR: 2.81, 95% CI: 1.32 to 3.01; ), smoking status (OR: 3.2, 95% CI: 1.35 to 7.56; ), and blood transfusion (OR: 3.15, 95% CI: 1.45 to 6.84; ) were independently associated with POCs. RL resection, intraoperative blood transfusion, and smoking were associated with increased risk for POCs in donors. Helry L. Candido, Eduardo A. da Fonseca, Flávia H. Feier, Renata Pugliese, Marcel A. Benavides, Enis D. Silva, Karina Gordon, Marcelo Gama de Abreu, Jaume Canet, Paulo Chapchap, and Joao Seda Neto Copyright © 2015 Helry L. Candido et al. All rights reserved. Plasma Exchange for the Recurrence of Primary Focal Segmental Glomerulosclerosis in Adult Renal Transplant Recipients: A Meta-Analysis Mon, 30 Nov 2015 06:33:50 +0000 Background. Posttransplant recurrence of primary focal segmental glomerulosclerosis (rFSGS) in the form of massive proteinuria is not uncommon and has detrimental consequences on renal allograft survival. A putative circulating permeability factor has been implicated in the pathogenesis leading to widespread use of plasma exchange (PLEX). We reviewed published studies to assess the role of PLEX on treatment of rFSGS in adults. Methods. Eligible manuscripts compared PLEX or variants with conventional care for inducing proteinuria remission (PR) in rFSGS and were identified through MEDLINE and reference lists. Data were abstracted in parallel by two reviewers. Results. We detected 6 nonrandomized studies with 117 cases enrolled. In a random effects model, the pooled risk ratio for the composite endpoint of partial or complete PR was 0,38 in favour of PLEX (95% CI: 0,23–0,61). No statistical heterogeneity was observed among included studies (%, = 0,42). On average, 9–26 PLEX sessions were performed to achieve PR. Renal allograft loss due to recurrence was lower (range: 0%–67%) in patients treated with PLEX. Conclusion. Notwithstanding the inherent limitations of small, observational trials, PLEX appears to be effective for PR in rFSGS. Additional research is needed to further elucidate its optimal use and impact on long-term allograft survival. Georgios Vlachopanos, Argyrios Georgalis, and Harikleia Gakiopoulou Copyright © 2015 Georgios Vlachopanos et al. All rights reserved. Psychosocial Status of Liver Transplant Candidates in Iran and Its Correlation with Health-Related Quality of Life and Depression and Anxiety Sun, 15 Nov 2015 11:10:53 +0000 Objectives. The study was aimed at providing a psychosocial profile for Iranian liver transplant candidates referred to an established liver transplantation program. Material and Methods. Patients assessed for liver transplant candidacy in Imam Khomeini Hospital (Tehran, Iran) between March 2013 and September 2014 were included. The following battery of tests were administered: Psychosocial Assessment of Candidates for Transplant (PACT), the Short-Form health survey (SF-36), and Hospital Anxiety and Depression Scale (HADS). Results. Psychosocial assessment in 205 liver transplant candidates revealed significant impairments in several SF-36 domains; social functioning was the least and physical functioning was the most impaired domains. The prevalence of cases with probable anxiety and depressive disorders, according to HADS, was 13.8% and 5.6%, respectively. According to PACT, 24.3% of the assessed individuals were considered good or excellent candidates. In 11.2%, transplantation seemed poor candidate due to at least one major psychosocial or lifestyle risk factor. Poor candidate quality was associated with impaired health-related quality of life and higher scores on anxiety and depression scales (). Conclusions. Transplant programs could implement specific intervention programs based on normative databases to address the psychosocial issues in patients in order to improve patient care, quality of life, and transplant outcomes. Maryam Banihashemi, Mohsen Hafezi, Mohsen Nasiri-Toosi, Ali Jafarian, Mohammad Reza Abbasi, Mohammad Arbabi, Maryam Abdi, Mahzad Khavarian, and Ali-Akbar Nejatisafa Copyright © 2015 Maryam Banihashemi et al. All rights reserved. Influence of Deceased Donor and Pretransplant Recipient Parameters on Early Overall Kidney Graft-Survival in Germany Sun, 11 Oct 2015 12:54:08 +0000 Background. Scarcity of grafts for kidney transplantation (KTX) caused an increased consideration of deceased donors with substantial risk factors. There is no agreement on which ones are detrimental for overall graft-survival. Therefore, we investigated in a nationwide multicentre study the impact of donor and recipient related risks known before KTX on graft-survival based on the original data used for allocation and graft acceptance. Methods. A nationwide deidentified multicenter study-database was created of data concerning kidneys donated and transplanted in Germany between 2006 and 2008 as provided by the national organ procurement organization (Deutsche Stiftung Organtransplantation) and BQS Institute. Multiple Cox regression (significance level 5%, hazard ratio [95% CI]) was conducted (, isolated KTX). Results. Risk factors associated with graft-survival were donor age (1.020 [1.013–1.027] per year), donor size (0.985 [0.977–0.993] per cm), donor’s creatinine at admission (1.002 [1.001–1.004] per µmol/L), donor treatment with catecholamine (0.757 [0.635–0.901]), and reduced graft-quality at procurement (1.549 [1.217–1.973]), as well as recipient age (1.012 [1.003–1.021] per year), actual panel reactive antibodies (1.007 [1.002–1.011] per percent), retransplantation (1.850 [1.484–2.306]), recipient’s cardiovascular comorbidity (1.436 [1.212–1.701]), and use of IL2-receptor antibodies for induction (0.741 [0.619–0.887]). Conclusion. Some donor characteristics persist to impact graft-survival (e.g., age) while the effect of others could be mitigated by elaborate donor-recipient match and care. Carl-Ludwig Fischer-Fröhlich, Marcus Kutschmann, Johanna Feindt, Irene Schmidtmann, Günter Kirste, Nils R. Frühauf, Ulrike Wirges, Axel Rahmel, and Christina Schleicher Copyright © 2015 Carl-Ludwig Fischer-Fröhlich et al. All rights reserved. Delayed Graft Function in Kidney Transplants: Time Evolution, Role of Acute Rejection, Risk Factors, and Impact on Patient and Graft Outcome Thu, 10 Sep 2015 07:24:27 +0000 Background. Although numerous risk factors for delayed graft function (DGF) have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE) occurring during the DGF period is ill-defined and DGF impact on patient and graft outcome remains controversial. Methods. From 1983 to 2014, 1784 kidney-only transplantations from deceased donors were studied. Classical risk factors for DGF along with two novel ones, recipient’s perioperative saline loading and residual diuresis, were analyzed by logistic regression and receiver operating characteristic (ROC) curves. Results. Along with other risk factors, absence of perioperative saline loading increases acute rejection incidence (OR = 1.9 [1.2–2.9]). Moreover, we observed two novel risk factors for DGF: patient’s residual diuresis ≤500 mL/d (OR = 2.3 [1.6–3.5]) and absence of perioperative saline loading (OR = 3.3 [2.0–5.4]). Area under the curve of the ROC curve (0.77 [0.74–0.81]) shows an excellent discriminant power of our model, irrespective of rejection. DGF does not influence patient survival . However, graft survival is decreased only when rejection was associated with DGF .  Conclusions. Perioperative saline loading efficiently prevents ischemia-reperfusion injury, which is the predominant factor inducing DGF. DGF per se has no influence on patient and graft outcome. Its incidence is currently close to 5% in our centre. Martin Chaumont, Judith Racapé, Nilufer Broeders, Fadoua El Mountahi, Annick Massart, Thomas Baudoux, Jean-Michel Hougardy, Dimitri Mikhalsky, Anwar Hamade, Alain Le Moine, Daniel Abramowicz, and Pierre Vereerstraeten Copyright © 2015 Martin Chaumont et al. All rights reserved. Alternative Living Kidney Donation Programs Boost Genetically Unrelated Donation Wed, 02 Sep 2015 09:11:16 +0000 Donor-recipient ABO and/or HLA incompatibility used to lead to donor decline. Development of alternative transplantation programs enabled transplantation of incompatible couples. How did that influence couple characteristics? Between 2000 and 2014, 1232 living donor transplantations have been performed. In conventional and ABO-incompatible transplantation the willing donor becomes an actual donor for the intended recipient. In kidney-exchange and domino-donation the donor donates indirectly to the intended recipient. The relationship between the donor and intended recipient was studied. There were 935 conventional and 297 alternative program transplantations. There were 66 ABO-incompatible, 68 domino-paired, 62 kidney-exchange, and 104 altruistic donor transplantations. Waiting list recipients () were excluded as they did not bring a living donor. 1131 couples remained of whom 196 participated in alternative programs. Genetically unrelated donors (486) were primarily partners. Genetically related donors (645) were siblings, parents, children, and others. Compared to genetically related couples, almost three times as many genetically unrelated couples were incompatible and participated in alternative programs (). 62% of couples were genetically related in the conventional donation program versus 32% in alternative programs (). Patient and graft survival were not significantly different between recipient programs. Alternative donation programs increase the number of transplantations by enabling genetically unrelated donors to donate. Rosalie A. Poldervaart, Mirjam Laging, Tessa Royaards, Judith A. Kal-van Gestel, Madelon van Agteren, Marry de Klerk, Willij Zuidema, Michiel G. H. Betjes, and Joke I. Roodnat Copyright © 2015 Rosalie A. Poldervaart et al. All rights reserved. Boceprevir-Based Triple Antiviral Therapy for Chronic Hepatitis C Virus Infection in Kidney-Transplant Candidates Thu, 16 Jul 2015 11:17:07 +0000 Background. There are few data on the combination of (pegylated-) interferon- (Peg-IFN-) α, ribavirin, and first-generation direct-acting antiviral agents (DAAs). Our aim was to describe the efficacy and safety of Peg-IFN-α, ribavirin, and boceprevir in hemodialysis patients. Patients. Six hemodialysis patients, chronically infected by genotype-1 HCV, were given Peg-IFN-α (135 µg/week), ribavirin (200 mg/d), and boceprevir (2400 mg/d) for 48 weeks. Results. At initiation of antiviral therapy, median viral concentration was 5.68 (3.78–6.55) log IU/mL. HCV RNA was undetectable in four of the six patients at week 4 and in all patients at week 24. A breakthrough was observed in two patients between weeks 24 and 48, and a third patient stopped antiviral therapy between weeks 24 and 48 because of severe peripheral neuropathy. At week 48, HCV RNA was undetectable in three patients. Of these, two patients relapsed within a month after antiviral therapy was stopped. Hence, only one patient had a sustained virological response; he was a previous partial responder. Overall, anemia was the main side effect. Conclusion. A triple antiviral therapy based on Peg-IFN-α, ribavirin, and boceprevir is not optimal at treating hemodialysis patients with chronic HCV infection. Studies using new-generation drugs are required in this setting. Mireille Mehawej, Lionel Rostaing, Laurent Alric, Arnaud Del Bello, Jacques Izopet, and Nassim Kamar Copyright © 2015 Mireille Mehawej et al. All rights reserved. Factors Associated with Uncontrolled Hypertension among Renal Transplant Recipients Attending Nephrology Clinics in Nairobi, Kenya Tue, 14 Jul 2015 11:38:31 +0000 Objective. To determine the factors associated with poor blood pressure control among renal transplant recipients in a resource-limited setting. Methods. A cross-sectional study was carried out on renal transplant recipients at the Kenyatta National Hospital. Sociodemographic details, blood pressure, urine albumin : creatinine ratio, and adherence using the MMAS-8 questionnaire were noted. Independent factors associated with uncontrolled hypertension were determined using logistic regression analysis. Results. 85 subjects were evaluated. Mean age was 42.4 (SD ± 12.2) years, with a male : female ratio of 1.9 : 1. Fifty-five patients (64.7%) had uncontrolled hypertension (BP ≥ 130/80 mmHg). On univariate analysis, male sex (OR 3.7, 95% CI 1.4–9.5, ), higher levels of proteinuria (), and nonadherence to antihypertensives (OR 18, 95% CI 5.2–65.7, ) were associated with uncontrolled hypertension. On logistic regression analysis, male sex (adjusted OR 4.6, 95% CI 1.1–19.0, ) and nonadherence (adjusted OR 33.8, 95% CI 8.6–73.0, ) were independently associated with uncontrolled hypertension. Conclusion. Factors associated with poor blood pressure control in this cohort were male sex and nonadherence to antihypertensives. Emphasis on adherence to antihypertensive therapy must be pursued within this population. Mary N. Kubo, Joshua K. Kayima, Anthony J. Were, Seth O. McLigeyo, and Elijah N. Ogola Copyright © 2015 Mary N. Kubo et al. All rights reserved. Proximal Tubular Injury in Medullary Rays Is an Early Sign of Acute Tacrolimus Nephrotoxicity Wed, 24 Jun 2015 08:25:33 +0000 Tacrolimus (FK506) is one of the principal immunosuppressive agents used after solid organ transplantations to prevent allograft rejection. Chronic renal injury induced by tacrolimus is characterized by linear fibrosis in the medullary rays; however, the early morphologic findings of acute tacrolimus nephrotoxicity are not well characterized. Kidney injury molecule-1 (KIM-1) is a specific injury biomarker that has been proven to be useful in the diagnosis of mild to severe acute tubular injury on renal biopsies. This study was motivated by a patient with acute kidney injury associated with elevated serum tacrolimus levels in whom KIM-1 staining was present only in proximal tubules located in the medullary rays in the setting of otherwise normal light, immunofluorescent, and electron microscopy. We subsequently evaluated KIM-1 expression in 45 protocol and 39 indicated renal transplant biopsies to determine whether higher serum levels of tacrolimus were associated with acute segment specific injury to the proximal tubule, as reflected by KIM-1 staining in the proximal tubules of the cortical medullary rays. The data suggest that tacrolimus toxicity preferentially affects proximal tubules in medullary rays and that this targeted injury is a precursor lesion for the linear fibrosis seen in chronic tacrolimus toxicity. Diane Cosner, Xu Zeng, and Ping L. Zhang Copyright © 2015 Diane Cosner et al. All rights reserved. MicroRNAs in Kidney Transplantation: Living up to Their Expectations? Mon, 11 May 2015 13:21:41 +0000 Since the discovery of microRNAs, ample research has been conducted to elucidate their involvement in an array of (patho)physiological conditions. Ischemia reperfusion injury is a major problem in kidney transplantation and its mechanism is still not fully known, nor is there an effective therapy. Furthermore, no biomarker is available to specifically measure (ischemic) damage after kidney transplantation or predict transplantation outcome. In this review, we summarize studies conducted on microRNAs in renal ischemia reperfusion injury and kidney transplantation. Although the number of publications on miRNAs in different areas of nephrology is increasing every year, only a limited number of reports that address the role of miRNAs in relation to ischemia reperfusion injury or kidney transplantation are available. All reports up to June 2014 on microRNAs in renal IRI, kidney transplantation, and renal allograft status were included. Design of the studies was highly variable and there was limited overlap between microRNAs found in these reports. No single microRNA expression pattern could be found, although multiple microRNAs involved in the immune response seem to be altered after ischemia reperfusion injury and kidney transplantation. Although there is a growing interest in microRNA research in kidney transplantation aiming to identify biomarkers and therapeutical targets, to date, no specific microRNA has been demonstrated to be applicable as either one, mostly because of lack of specificity. More systematical research is needed to determine whether microRNAs can be applied as biomarker, therapeutic target, or therapeutic agent in kidney transplantation. Eline K. van den Akker, Frank J. M. F. Dor, Jan N. M. IJzermans, and Ron W. F. de Bruin Copyright © 2015 Eline K. van den Akker et al. All rights reserved. Breakdown in the Organ Donation Process and Its Effect on Organ Availability Thu, 09 Apr 2015 10:54:44 +0000 Background. This study examines the effect of breakdown in the organ donation process on the availability of transplantable organs. A process breakdown is defined as a deviation from the organ donation protocol that may jeopardize organ recovery. Methods. A retrospective analysis of donation-eligible decedents was conducted using data from an independent organ procurement organization. Adjusted effect of process breakdown on organs transplanted from an eligible decedent was examined using multivariable zero-inflated Poisson regression. Results. An eligible decedent is four times more likely to become an organ donor when there is no process breakdown (adjusted OR: 4.01; 95% CI: 1.6838, 9.6414; ) even after controlling for the decedent’s age, gender, race, and whether or not a decedent had joined the state donor registry. However once the eligible decedent becomes a donor, whether or not there was a process breakdown does not affect the number of transplantable organs yielded. Overall, for every process breakdown occurring in the care of an eligible decedent, one less organ is available for transplant. Decedent’s age is a strong predictor of likelihood of donation and the number of organs transplanted from a donor. Conclusion. Eliminating breakdowns in the donation process can potentially increase the number of organs available for transplant but some organs will still be lost. Manik Razdan, Howard B. Degenholtz, Jeremy M. Kahn, and Julia Driessen Copyright © 2015 Manik Razdan et al. All rights reserved. The Benefit of Sirolimus Maintenance Immunosuppression and Rabbit Antithymocyte Globulin Induction in Liver Transplant Recipients That Develop Acute Kidney Injury in the Early Postoperative Period Wed, 11 Mar 2015 09:26:42 +0000 Published data are limited describing renal outcomes in orthotopic liver transplant (OLT) recipients prescribed sirolimus (SRL) maintenance immunosuppression (MIS) and rabbit antithymocyte globulin (rATG) induction. We investigated whether SRL MIS and rATG induction facilitated recovery of acute kidney injury in the early postoperative period. This retrospective descriptive study screened 308 consecutive OLTs performed between 2006 and 2009. All patients received rATG induction with steroid avoidance. MIS consisted of SRL or TAC with mycophenolate mofetil. A total of 197 patients were included: 168 (85%) received TAC and 29 (15%) received SRL for a median of 365 days. Demographics were similar between groups except for a higher incidence of pretransplant renal dysfunction in the SRL recipients (SRL 59% versus TAC 21%; ). The eGFR was significantly () higher for all time points in the TAC group with the exception of month 2. However, improvement in eGFR was significantly () greater in the SRL group postoperatively. Our study suggests that rATG induction and SRL maintenance immunosuppression facilitate renal recovery for liver transplant recipients that develop acute kidney injury in the early postoperative period. Benjamin T. Duhart Jr., Winston A. Ally, Amy G. Krauss, Joanna Q. Hudson, James D. Eason, Vinaya Rao, and Jason M. Vanatta Copyright © 2015 Benjamin T. Duhart Jr. et al. All rights reserved. A Nationwide Assessment of the Burden of Urinary Tract Infection among Renal Transplant Recipients Wed, 25 Feb 2015 12:41:45 +0000 Objective. Evaluate the prevalence and outcomes of urinary tract infection (UTI) among renal transplant recipients. Methods. A secondary analysis of the Nationwide Inpatient Sample 2009–2011 was conducted. Survey-weighted multivariable regression analyses were used to examine the impact of UTI on transplant complications, total charges, and length of stay. Results. A total of 1,044 renal transplant recipients, representing a population estimate of 49,862, were included in the study. UTI was most common in transplant recipients with hypertension (53%) and prevalence was noted to be 28.2 and 65.9 cases per 1,000 for men and women, respectively. UTI increased the likelihood of transplant complications (182% for men, 169% for women). Total charges were 28% higher among men as compared to 22% among women with UTI. Such infection also increased the length of stay by 87% among men and 74% among women. Discussion. UTI in renal transplant recipients was associated with prolonged length of stay, total charges, and increased odds of transplant complications. Interventions to prevent UTI among such patients should be a priority area for future research and practice. Benjamin J. Becerra, Monideepa B. Becerra, and Nasia Safdar Copyright © 2015 Benjamin J. Becerra et al. All rights reserved. Risk-Adjusted Analysis of Relevant Outcome Drivers for Patients after More Than Two Kidney Transplants Sun, 01 Feb 2015 09:10:18 +0000 Renal transplantation is the treatment of choice for patients suffering end-stage renal disease, but as the long-term renal allograft survival is limited, most transplant recipients will face graft loss and will be considered for a retransplantation. The goal of this study was to evaluate the patient and graft survival of the 61 renal transplant recipients after second or subsequent renal transplantation, transplanted in our institution between 1990 and 2010, and to identify risk factors related to inferior outcomes. Actuarial patient survival was 98.3%, 94.8%, and 88.2% after one, three, and five years, respectively. Actuarial graft survival was 86.8%, 80%, and 78.1% after one, three, and five years, respectively. Risk-adjusted analysis revealed that only age at the time of last transplantation had a significant influence on patient survival, whereas graft survival was influenced by multiple immunological and surgical factors, such as the number of HLA mismatches, the type of immunosuppression, the number of surgical complications, need of reoperation, primary graft nonfunction, and acute rejection episodes. In conclusion, third and subsequent renal transplantation constitute a valid therapeutic option, but inferior outcomes should be expected among elderly patients, hyperimmunized recipients, and recipients with multiple operations at the site of last renal transplantation. Lampros Kousoulas, Florian W. R. Vondran, Paulina Syryca, Juergen Klempnauer, Harald Schrem, and Frank Lehner Copyright © 2015 Lampros Kousoulas et al. All rights reserved. Interstitial Lung Disease Associated with mTOR Inhibitors in Solid Organ Transplant Recipients: Results from a Large Phase III Clinical Trial Program of Everolimus and Review of the Literature Thu, 18 Dec 2014 00:10:30 +0000 Interstitial lung disease (ILD) has been reported with the use of mammalian target of rapamycin inhibitors (mTORi). The clinical and safety databases of three Phase III trials of everolimus in de novo kidney (A2309), heart (A2310), and liver (H2304) transplant recipients (TxR) were searched using a standardized MedDRA query (SMQ) search for ILD followed by a case-by-case medical evaluation. A literature search was conducted in MEDLINE and EMBASE. Out of the 1,473 de novo TxR receiving everolimus in Phase III trials, everolimus-related ILD was confirmed in six cases (one kidney, four heart, and one liver TxR) representing an incidence of 0.4%. Everolimus was discontinued in three of the four heart TxR, resulting in ILD improvement or resolution. Outcome was fatal in the kidney TxR (in whom everolimus therapy was continued) and in the liver TxR despite everolimus discontinuation. The literature review identified 57 publications on ILD in solid organ TxR receiving everolimus or sirolimus. ILD presented months or years after mTORi initiation and symptoms were nonspecific and insidious. The event was more frequent in patients with a late switch to mTORi. In most cases, ILD was reversed after prompt mTORi discontinuation. ILD induced by mTORi is an uncommon and potentially fatal event warranting early recognition and drug discontinuation. Patricia Lopez, Sven Kohler, and Seema Dimri Copyright © 2014 Patricia Lopez et al. All rights reserved. The Impact of the Introduction of MELD on the Dynamics of the Liver Transplantation Waiting List in São Paulo, Brazil Thu, 27 Nov 2014 11:58:49 +0000 Until July 15, 2006, the time on the waiting list was the main criterion for allocating deceased donor livers in the state of São Paulo, Brazil. After this date, MELD has been the basis for the allocation of deceased donor livers for adult transplantation. Our aim was to compare the waitlist dynamics before MELD (1997–2005) and after MELD (2006–2012) in our state. A retrospective study was conducted including the data from all the liver transplant candidate waiting lists from July 1997 to December 2012. The data were related to the actual number of liver transplantations (Tr), the incidence of new patients on the list (I), and the number of patients who died while being on the waitlist (D) from 1997 to 2005 (the pre-MELD era) and from 2006 to 2012 (the post-MELD era). The number of transplantations from 1997 to 2005 and from 2006 to 2012 increased nonlinearly, with a clear trend to levelling to equilibrium at approximately 350 and 500 cases per year, respectively. The implementation of the MELD score resulted in a shorter waiting time until liver transplantation. Additionally, there was a significant effect on the waitlist dynamics in the first 4 years; however, the curves diverge from there, implying a null long-range effect on the waitlist by the MELD scores. Eleazar Chaib, Eduardo Massad, Bruno Butturi Varone, Andre Leopoldino Bordini, Flavio Henrique Ferreira Galvão, Alessandra Crescenzi, Arnaldo Bernal Filho, and Luiz Augusto Carneiro D’Albuquerque Copyright © 2014 Eleazar Chaib et al. All rights reserved. Outcomes of Renal Transplantation in Brunei Darussalam over a Twenty-Year Period (1993–2012) Wed, 12 Nov 2014 11:51:43 +0000 Objectives. Brunei Darussalam has a high prevalence and incidence of end stage renal disease (ESRD). Up until 2012, all renal transplantations were performed in overseas centres, either as government-sponsored (living-related transplantation) or as self-sponsored (commercialized transplantation) ones. We hypothesize that graft and patient survival of Brunei renal transplant patients are on a par with international standards. Materials and Methods. Data of all renal transplant patients in Brunei were analysed over a twenty-year period from registry records and case notes. Comparative survival data from other countries were obtained from PubMed-listed literature. Results. A total of 49 transplantation procedures were performed in foreign centres between 1993 and 2012. 29 were government-sponsored and 20 were self-sponsored transplantations. The 5- and 10-year overall patient survival rates were 93.3% and 90.1%, respectively. The 5- and 10-year overall graft survival rates were 91.1% and 81.2%. There is no difference in the survival outcomes of government-sponsored and self-sponsored patients. Living-related (government-sponsored) and commercialised (self-sponsored) grafts had equivalent survival to those reported in the literature. Conclusion. Our survival data was on par with those achieved in many countries. We hope to use this information to convince local stakeholders and patients to favour transplantation as the preferred modality of RRT. Jackson Tan, Muhammad Abdul Mabood Khalil, Si Yen Tan, Muhammad Khalil, Dalinatul Ahmed, Shaukat Zinna, and William Chong Copyright © 2014 Jackson Tan et al. All rights reserved. Methotrexate for the Treatment of Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation Mon, 27 Oct 2014 09:15:56 +0000 Glucocorticoids have been the primary treatment of graft-versus-host disease (GVHD) over the past decade. Complete responses to steroid therapy are usually expected in almost one-third of aGVHD cases and partial response is anticipated in another one-third of patients. However, for those patients not responding to corticosteroid treatment, there is no standard second-line therapy for acute or chronic GVHD. Methotrexate (MTX) for treatment of steroid refractory GVHD has been evaluated in a number of studies. Results from peer-reviewed original articles were identified and the pooled data analyzed. Despite several limitations in data collection and analysis, weekly administration of methotrexate at a median dose of 7.5 mg/m2 seems to be safe with minimal toxicities in the context of both aGVHD and cGVHD treatments. The observed overall response (OR) in patients with aGVHD to MTX treatment in the published studies was 69.9%, with complete response (CR) in 59.2% and PR in 10.6%. In cGVHD the OR was 77.6%, with CR reported in 49.6% and PR in 28% of patients. Predictors of better responses were lower grade GVHD, cutaneous involvement, and isolated organ involvement. MTX as a steroid sparing agent might reduce long-term complications and improve the quality of life of GVHD affected individuals. Amr Nassar, Ghada Elgohary, Tusneem Elhassan, Zubeir Nurgat, Said Y. Mohamed, and Mahmoud Aljurf Copyright © 2014 Amr Nassar et al. All rights reserved. Preconditioning Serum Levels of Endothelial Cell-Derived Molecules and the Risk of Posttransplant Complications in Patients Treated with Allogeneic Stem Cell Transplantation Wed, 08 Oct 2014 12:38:38 +0000 Endothelial cells are involved in the pathogenesis of acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. These cells express several molecules that can be detected as biologically active soluble forms; serum levels of these molecules may thereby reflect the functional status of endothelial cells. Furthermore, acute GVHD is an inflammatory reaction and endothelial cells function as local regulators of inflammation. We therefore investigated whether differences in preconditioning/pretransplant serum levels of endothelium-expressed molecules (i.e., endocan, vascular cell adhesion molecule 1 (VCAM-1), and E-selectin) were associated with a risk of posttransplant GVHD. Our study should be regarded as a population-based study of consecutive and thereby unselected patients (). Analysis of this pretreatment endothelium biomarker profile by unsupervised hierarchical clustering identified a subset of patients with increased early nonrelapse mortality. Furthermore, low endocan levels were significantly associated with acute GVHD in the liver and gastrointestinal tract, whereas high VCAM-1 levels were associated with acute GVHD in the skin only. Our study suggests that the preconditioning/pretransplant status of endothelial cells (possibly through altered trafficking of immunocompetent cells) is important for the risk and the organ involvement of later acute GVHD. Roald Lindås, Tor Henrik Andersson Tvedt, Kimberley Joanne Hatfield, Håkon Reikvam, and Øystein Bruserud Copyright © 2014 Roald Lindås et al. All rights reserved. Attitude of Healthcare Professionals: A Major Limiting Factor in Organ Donation from Brain-Dead Donors Tue, 30 Sep 2014 00:00:00 +0000 Public attitude toward deceased donor organ recovery in Poland is quite positive, with only 15% opposing to donation of their own organs, yet actual donation rate is only 16/pmp. Moreover, donation rate varies greatly (from 5 to 28 pmp) in different regions of the country. To identify the barriers of organ donation, we surveyed 587 physicians involved in brain death diagnosis from regions with low (LDR) and high donation rates (HDR). Physicians from LDR were twice more reluctant to start diagnostic procedure when clinical signs of brain death were present (14% versus 5.5% physicians from HDR who would not diagnose death, resp.). Twenty-five percent of LDR physicians (as opposed to 12% of physicians from HDR) would either continue with intensive therapy or confirm brain death and limit to the so-called minimal therapy. Only 32% of LDR physicians would proceed with brain death diagnosis regardless of organ donation, compared to 67% in HDR. When donation was not an option, mechanical ventilation would be continued more often in LDR regions (43% versus 26.7%; . In conclusion, low donation activity seems to be mostly due to medical staff attitude. Maciej Kosieradzki, Anna Jakubowska-Winecka, Michal Feliksiak, Ilona Kawalec, Ewa Zawilinska, Roman Danielewicz, Jaroslaw Czerwinski, Piotr Malkowski, and Wojciech Rowiński Copyright © 2014 Maciej Kosieradzki et al. All rights reserved. Ureteral Stent Placement Increases the Risk for Developing BK Viremia after Kidney Transplantation Thu, 11 Sep 2014 08:44:31 +0000 The placement of ureteral stent (UrSt) at kidney transplantation reduces major urological complications but increases the risk for developing nephropathy from the BK virus. It is unclear whether UrSt placement increases nephropathy risk by increasing risk of precursor viral replication or by other mechanisms. We retrospectively investigated whether UrSt placement increased the risk for developing BK Viremia (BKVM) in adult and pediatric kidney transplants performed at the University of Florida between July 1, 2007, and December 31, 2010. In this period all recipients underwent prospective BKV PCR monitoring and were maintained on similar immunosuppression. Stent placement or not was based on surgeon preference. In 621 transplants, UrSt were placed in 295 (47.5%). BKVM was seen in 22% versus 16% without UrSt (). In multivariate analyses, adjusting for multiple transplant covariates, only UrSt placement remained significantly associated with BKVM (). UrSt placement significantly increased the risk for BKVM. Routine UrSt placement needs to be revaluated, since benefits may be negated by the need for more BK PCR testing and potential for graft survival-affecting nephritis. Faris Hashim, Shehzad Rehman, Jon A. Gregg, and Vikas R. Dharnidharka Copyright © 2014 Faris Hashim et al. All rights reserved. A Novel Approach for the Enumeration of Peripheral Blood Stem Cells Suitable for Transplantation Tue, 05 Aug 2014 11:54:54 +0000 Stem cells have the capability to proliferate and differentiate into various cells of the body. Few stem cell sources have been approved for transplantation, among them are the hematopoietic progenitor cells which are progenitors of the myeloid and erythroid lineage in the hematopoietic system, that continually provides mature blood cells during the lifespan of the individual. These well-characterized stem cells are clinically relevant in the treatment of diseases such as breast cancer, leukemias, and congenital immunodeficiencies. Peripheral blood stem transplantation is a standard procedure after its first successful transplantation more than 35 years ago. The minimum intended dose of stem cells given to the patient is cells. In this study, we are establishing a correlation between the number of stem cells enumerated and the weight of the patient as a determinant for suitable transplantation. We have established a conversion factor to deliver the required dose of approximately stem cells/kg body weight. This will ensure a uniform collection strategy that is sufficient for transplantation irrespective of the weight of the patient. This approach, if incorporated, will lead to a significantly lesser rate of bone marrow transplantation failures as sufficient number of stem cells will ensure engraftment of stem cells. Winston Costa Pereira, Omar Alsuhaibani, Ghaleb Elyamany, and Abdulaziz Al Abdulaaly Copyright © 2014 Winston Costa Pereira et al. All rights reserved. Trends in the Management and Outcomes of Kidney Transplantation for Autosomal Dominant Polycystic Kidney Disease Sun, 03 Aug 2014 12:39:31 +0000 Background. Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder leading to end-stage renal failure. The objective of this study was to evaluate a longitudinal experience of kidney transplantation for ADPKD. Methods. A single center retrospective review of patients undergoing kidney transplantation was conducted, with comparisons across two time periods: early (02/2000–04/2007, ) and late (04/2007–08/2012, ). Results. Over the 13.5-year study period, 133 patients underwent transplantation for ADPKD. Overall, no significant difference between the early and late group with regard to intraoperative complications, need for reoperation, readmissions within 30 days, delayed graft function, and mortality was noted. There was a trend towards increase in one-year graft survival (early 93.1% versus late 100%, ). In the early group, 67% of recipients had undergone aneurysm screening, compared to 91% of recipients in the late group (). Conclusions. This study demonstrates consistent clinical care with a trend towards improved rates of one-year graft survival. Interestingly, we also note a significantly higher use of cerebral imaging over time, with the majority that were detected requiring surgical intervention which may justify the current practice of nonselective radiological screening until improved screening criteria are developed. Madhukar S. Patel, Praveen Kandula, David Wojciechowski, James F. Markmann, and Parsia A. Vagefi Copyright © 2014 Madhukar S. Patel et al. All rights reserved. Donor Heart Utilization following Cardiopulmonary Arrest and Resuscitation: Influence of Donor Characteristics and Wait Times in Transplant Regions Tue, 08 Jul 2014 00:00:00 +0000 Background. Procurement of hearts from cardiopulmonary arrest and resuscitated (CPR) donors for transplantation is suboptimal. We studied the influences of donor factors and regional wait times on CPR donor heart utilization. Methods. From UNOS database (1998 to 2012), we identified 44,744 heart donors, of which 4,964 (11%) received CPR. Based on procurement of heart for transplantation, CPR donors were divided into hearts procured (HP) and hearts not procured (HNP) groups. Logistic regression analysis was used to identify predictors of heart procurement. Results. Of the 4,964 CPR donors, 1,427 (28.8%) were in the HP group. Donor characteristics that favored heart procurement include younger age (25.5 ± 15 yrs versus 39 ± 18 yrs, ), male gender (34% versus 23%, ), shorter CPR duration (<15 min versus >30 min, ), and head trauma (60% versus 15%). Among the 11 UNOS regions, the highest procurement was in Region 1 (37%) and the lowest in Region 3 (24%). Regional transplant volumes and median waiting times did not influence heart procurement rates. Conclusions. Only 28.8% of CPR donor hearts were procured for transplantation. Factors favoring heart procurement include younger age, male gender, short CPR duration, and traumatic head injury. Heart procurement varied by region but not by transplant volumes or wait times. Mohammed Quader, Luke Wolfe, Gundars Katlaps, and Vigneshwar Kasirajan Copyright © 2014 Mohammed Quader et al. All rights reserved. Risk-Stratified Cardiovascular Screening Including Angiographic and Procedural Outcomes of Percutaneous Coronary Interventions in Renal Transplant Candidates Thu, 19 Jun 2014 10:14:40 +0000 Background. Benefits of cardiac screening in kidney transplant candidates (KTC) will be dependent on the availability of effective interventions. We retrospectively evaluated characteristics and outcome of percutaneous coronary interventions (PCI) in KTC selected for revascularization by a cardiac screening approach. Methods. In 267 patients evaluated 2003 to 2006, screening tests performed were reviewed and PCI characteristics correlated with major adverse cardiovascular events (MACE) during a follow-up of 55 months. Results. Stress tests in 154 patients showed ischemia in 28 patients (89% high risk). Of 58 patients with coronary angiography, 38 had significant stenoses and 18 cardiac interventions (6.7% of all). 29 coronary lesions in 17/18 patients were treated by PCI. Angiographic success rate was 93.1%, but procedural success rate was only 86.2%. Long lesions () and diffuse disease () were associated with MACE. In high risk patients, cardiac screening did not improve outcome as 21.7% of patients with versus 15.5% of patients without properly performed cardiac screening had MACE (). Conclusion. The moderate procedural success of PCI and poor outcome in long and diffuse coronary lesions underscore the need to define appropriate revascularization strategies in KTC, which will be a prerequisite for cardiac screening to improve outcome in these high-risk patients. Julian König, Martin Möckel, Eda Mueller, Wolfgang Bocksch, Seema Baid-Agrawal, Nina Babel, Ralf Schindler, Petra Reinke, and Peter Nickel Copyright © 2014 Julian König et al. All rights reserved. Peak Serum AST Is a Better Predictor of Acute Liver Graft Injury after Liver Transplantation When Adjusted for Donor/Recipient BSA Size Mismatch (ASTi) Mon, 09 Jun 2014 09:04:13 +0000 Background. Despite the marked advances in the perioperative management of the liver transplant recipient, an assessment of clinically significant graft injury following preservation and reperfusion remains difficult. In this study, we hypothesized that size-adjusted AST could better approximate real AST values and consequently provide a better reflection of the extent of graft damage, with better sensitivity and specificity than current criteria. Methods. We reviewed data on 930 orthotopic liver transplant recipients. Size-adjusted AST (ASTi) was calculated by dividing peak AST by our previously reported index for donor-recipient size mismatch, the BSAi. The predictive value of ASTi of primary nonfunction (PNF) and graft survival was assessed by receiver operating characteristic curve, logistic regression, Kaplan-Meier survival, and Cox proportional hazard model. Results. Size-adjusted peak AST (ASTi) was significantly associated with subsequent occurrence of PNF and graft failure. In our study cohort, the prediction of PNF by the combination of ASTi and PT-INR had a higher sensitivity and specificity compared to current UNOS criteria. Conclusions. We conclude that size-adjusted AST (ASTi) is a simple, reproducible, and sensitive marker of clinically significant graft damage. Kyota Fukazawa, Seigo Nishida, and Ernesto A. Pretto Jr. Copyright © 2014 Kyota Fukazawa et al. All rights reserved. Resolution of Mild Ganciclovir-Resistant Cytomegalovirus Disease with Reduced-Dose Cidofovir and CMV-Hyperimmune Globulin Sun, 01 Jun 2014 11:19:29 +0000 Ganciclovir-resistant cytomegalovirus (CMV) is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by “indirect” viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative) kidney transplant patients diagnosed with ganciclovir-resistant CMV disease. All patients initially developed “breakthrough” viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2 mg/kg) cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV. Samir J. Patel, Samantha A. Kuten, Richard J. Knight, Dana M. Hong, and A. Osama Gaber Copyright © 2014 Samir J. Patel et al. All rights reserved. Adjuvant Ciprofloxacin for Persistent BK Polyomavirus Infection in Kidney Transplant Recipients Thu, 08 May 2014 13:07:00 +0000 Background. BK virus (BKV) infection is a common complication following kidney transplantation. Immunosuppression reduction is the cornerstone of treatment while adjuvant drugs have been tried in small uncontrolled studies. We sought to examine our center’s experience with the use of ciprofloxacin in patients with persistent BKV infection. Methods. Retrospective evaluation of the effect of a 30-day ciprofloxacin course (250 mg twice daily) on BKV infection in kidney transplant recipients who had been diagnosed with BK viruria ≥106 copies/mL and viremia ≥500 copies/mL and in whom the infection did not resolve after immunosuppression reduction and/or treatment with other adjuvant agents. BKV in plasma and urine was evaluated after 3 months following treatment with ciprofloxacin. Results. Nine kidney transplant recipients received ciprofloxacin at a median of 130 days following the initial reduction in immunosuppression. Three patients showed complete viral clearance and another 3 had a ≥50% decrease in plasma viral load. No serious adverse events secondary to ciprofloxacin were reported and no grafts were lost due to BKV up to 1 year after treatment. Conclusion. Ciprofloxacin may be a useful therapy for persistent BKV infection despite conventional treatment. Randomized trials are required to evaluate the potential benefit of this adjuvant therapy. David Arroyo, Sindhu Chandran, Parsia A. Vagefi, and David Wojciechowski Copyright © 2014 David Arroyo et al. All rights reserved.