Journal of Transplantation The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . 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. Anemia Control in Kidney Transplant Recipients Using Once-Monthly Continuous Erythropoietin Receptor Activator: A Prospective, Observational Study Sun, 04 May 2014 12:52:04 +0000 In a multicenter, prospective, observational study of 279 kidney transplant recipients with anemia, the efficacy and safety of once-monthly continuous erythropoietin receptor activator (C.E.R.A.) were assessed to a maximum of 15 months. The main efficacy variable was the proportion of patients achieving a hemoglobin level of 11-12 g/dL at each of visits between months 7 and 9. At study entry, 224 patients (80.3%) were receiving erythropoiesis stimulating agent (ESA) therapy including darbepoetin alfa (98), epoetin beta (61), and C.E.R.A. (45). The mean (SD) time between C.E.R.A. applications was 34.0 (11.9) days. Among 193 patients for whom efficacy data were available, mean (SD) hemoglobin was 11.1 (0.99) g/dL at study entry, 11.5 (1.1) g/dL at month 7, 11.6 (1.3) g/dL at month 9, and 11.4 (1.1) g/dL at month 15. During months 7–9, 20.7% of patients had all hemoglobin values within the range 11-12 g/dL and 64.8% were within 10–13 g/dL. Seven patients (2.5%) discontinued C.E.R.A. due to adverse events or serious adverse events. In this observational trial under real-life conditions, once-monthly C.E.R.A. therapy achieved stable hemoglobin levels in stable kidney transplant recipients with good tolerability, and with no requirement for any dose change in 43% of patients. Klemens Budde, Thomas Rath, and Volker Kliem Copyright © 2014 Klemens Budde et al. All rights reserved. An Association between BK Virus Replication in Bone Marrow and Cytopenia in Kidney-Transplant Recipients Tue, 29 Apr 2014 09:36:41 +0000 The human polyomavirus BK (BKV) is associated with severe complications, such as ureteric stenosis and polyomavirus-associated nephropathy (PVAN), which often occur in kidney-transplant patients. However, it is unknown if BKV can replicate within bone marrow. The aim of this study was to search for BKV replication within the bone marrow of kidney-transplant patients presenting with a hematological disorder. Seventy-two kidney-transplant patients underwent bone-marrow aspiration for cytopenia. At least one virus was detected in the bone marrow of 25/72 patients (35%), that is, parvovirus B19 alone (n = 8), parvovirus plus Epstein-Barr virus (EBV) (n = 3), cytomegalovirus (n = 4), EBV (n = 2), BKV alone (n = 7), and BKV plus EBV (n = 1). Three of the eight patients who had BKV replication within the bone marrow had no detectable BKV replication in the blood. Neutropenia was observed in all patients with BKV replication in the bone marrow, and blockade of granulocyte maturation was observed. Hematological disorders disappeared in all patients after doses of immunosuppressants were reduced. In conclusion, an association between BKV replication in bone marrow and hematological disorders, especially neutropenia, was observed. Further studies are needed to confirm these findings. Emilie Pambrun, Catherine Mengelle, Geneviève Fillola, Patrick Laharrague, Laure Esposito, Isabelle Cardeau-Desangles, Arnaud Del Bello, Jacques Izopet, Lionel Rostaing, and Nassim Kamar Copyright © 2014 Emilie Pambrun et al. All rights reserved. Attitudes to Medication after Kidney Transplantation and Their Association with Medication Adherence and Graft Survival: A 2-Year Follow-Up Study Mon, 28 Apr 2014 07:38:14 +0000 Background. Nonadherence to medication is a common problem after kidney transplantation. The aim of this study was to explore attitudes towards medication, adherence, and the relationship with clinical outcomes. Method. Kidney recipients participated in a Q-methodological study 6 weeks after transplantation. As a measure of medication adherence, respondents completed the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS©-interview). Moreover, the intrapatient variability in the pharmacokinetics of tacrolimus was calculated, which measures stability of drug intake. Data on graft survival was retrieved from patient records up to 2 years after transplantation. Results. 113 renal transplant recipients (19–75 years old) participated in the study. Results revealed three attitudes towards medication adherence—attitude 1: “confident and accurate,” attitude 2: “concerned and vigilant,” and attitude 3: “appearance oriented and assertive.” We found association of attitudes with intrapatient variability in pharmacokinetics of tacrolimus, but not with self-reported nonadherence or graft survival. However, self-reported nonadherence immediately after transplantation was associated with lower two-year graft survival. Conclusion. These preliminary findings suggest that nonadherence shortly after kidney transplantation may be a risk factor for lower graft survival in the years to follow. The attitudes to medication were not a risk factor. Mirjam Tielen, Job van Exel, Mirjam Laging, Denise K. Beck, Roshni Khemai, Teun van Gelder, Michiel G. H. Betjes, Willem Weimar, and Emma K. Massey Copyright © 2014 Mirjam Tielen et al. All rights reserved. Use of Adjuvant Sorafenib in Liver Transplant Recipients with High-Risk Hepatocellular Carcinoma Thu, 10 Apr 2014 09:53:01 +0000 The efficacy of liver transplantation (LT) for hepatocellular (HCC) is limited by tumor recurrence rates of 10–15%. We undertook this pilot study to examine the use of sorafenib as adjuvant therapy in high-risk LT recipients. Methods. We prospectively enrolled patients transplanted for HCC into a treatment protocol utilizing sorafenib if their explant examination showed evidence of viable tumor exceeding Milan criteria. We utilized as historical controls patients transplanted previously, whose explant tumor characteristics exceeded Milan criteria, but who were not “preemptively” treated with sorafenib. Wilcoxon two-sample test and Fisher’s exact test were used to compare survival and recurrence rates between the two groups. Results. Seven patients were treated with sorafenib and compared to 12 historical “controls.” Two of 7 treated patients suffered from HCC recurrence. Of the comparison group, 9 experienced HCC recurrence and all succumbed to disease. Dose reduction improved tolerance of drug. The overall rate of HCC recurrence was decreased in the adjuvant therapy group compared to historical controls (29% versus 75%, ). Disease free 1-year survival for the treated versus untreated group was 100% versus 66%, respectively. Conclusion. Adjuvant use of sorafenib is safe and decreases risk of HCC recurrence in high-risk LT recipients. Kirti Shetty, Chiranjeev Dash, and Jacqueline Laurin Copyright © 2014 Kirti Shetty et al. All rights reserved. The Role of Imaging in Patient Selection, Preoperative Planning, and Postoperative Monitoring in Human Upper Extremity Allotransplantation Thu, 27 Mar 2014 16:26:49 +0000 Objective. To describe the role of imaging in vascular composite allotransplantation based on one institution’s experience with upper extremity allotransplant patients. Methods. The institutional review board approved this review of HIPAA-compliant patient data without the need for individual consent. A retrospective review was performed of imaging from 2008 to 2011 on individuals undergoing upper extremity transplantation. This demonstrated that, of the 19 patients initially considered, 5 patients with a mean age of 37 underwent transplantation. Reports were correlated clinically to delineate which preoperative factors lead to patient selection versus disqualification and what concerns dictated postoperative imaging. Findings were subdivided into musculoskeletal and vascular imaging criterion. Results. Within the screening phase, musculoskeletal exclusion criterion included severe shoulder arthropathy, poor native bone integrity, and marked muscular atrophy. Vascular exclusion criterion included loss of sufficient arterial or venous supply and significant distortion of the native vascular architecture. Postoperative imaging was used to document healing and hardware integrity. Postsurgical angiography and ultrasound were used to monitor for endothelial proliferation or thrombosis as signs of rejection and vascular complication. Conclusion. Multimodality imaging is an integral component of vascular composite allotransplantation surgical planning and surveillance to maximize returning form and functionality while minimizing possible complications. Eira S. Roth, David G. Buck, Vijay S. Gorantla, Joseph E. Losee, Daniel E. Foust, and Cynthia A. Britton Copyright © 2014 Eira S. Roth et al. All rights reserved. Midterm Experience of Ipsilateral Axillary-Axillary Arteriovenous Loop Graft as Tertiary Access for Haemodialysis Sun, 23 Mar 2014 09:09:10 +0000 Objectives. To present a series of ipsilateral axillary artery to axillary vein loop arm grafts as an alternative vascular access procedure for haemodialysis in patients with difficult access. Design. Retrospective case series. Methods. Patients who underwent an axillary loop arteriovenous graft from September 2009 to September 2012 were included. Preoperative venous imaging to exclude central venous stenosis and to image arm/axillary veins was performed. A cuffed PTFE graft was anastomosed to the distal axillary artery and axillary vein and looped on the arm. Results. 25 procedures were performed on 22 patients. Median age was 51 years, with 9 males and 13 females. Median number of previous access procedures was 3 (range 0–7). Median followup was 16.4 months (range 1–35). At 3 months and 1 year, the primary and secondary patency rates were 70% and 72% and 36% and 37%, respectively. There were 11 radiological interventions in 6 grafts including 5 angioplasties and 6 thrombectomies. There were 19 surgical procedures in 10 grafts, including thrombectomy, revision, repair for bleeding, and excision. Conclusions. Our series demonstrates that the axillary loop arm graft yields acceptable early patency rates in a complex group of patients but to maintain graft patency required high rates of surgical and radiological intervention, in particular graft thrombectomy. J. P. Hunter and M. L. Nicholson Copyright © 2014 J. P. Hunter and M. L. Nicholson. All rights reserved. Significance of Urinary Proteome Pattern in Renal Allograft Recipients Thu, 13 Mar 2014 13:37:58 +0000 Urinary proteomics is developing as a platform of urinary biomarkers of immense potential in recent years. The definition of urinary proteome in the context of renal allograft and characterization of different proteome patterns in various graft dysfunctions have led to the development of a distinct science of this noninvasive tool. Substantial numbers of studies have shown that different renal allograft disease states, both acute and chronic, could portray unique urinary proteome pattern enabling early diagnosis of graft dysfunction and proper manipulation of immunosuppressive strategy that could impact graft prognosis. The methodology of the urinary proteome is nonetheless not more complex than that of other sophisticated assays of conventional urinary protein analysis. Moreover, the need for a centralized database is also felt by the researchers as more and more studies have been presenting their results from different corners and as systems of organizing these newly emerging data being developed at international and national levels. In this context concept of urinary proteomics in renal allograft recipients would be of significant importance in clinical transplantation. Sufi M. Suhail Copyright © 2014 Sufi M. Suhail. All rights reserved. Three-Year Outcomes in Kidney Transplant Patients Randomized to Steroid-Free Immunosuppression or Steroid Withdrawal, with Enteric-Coated Mycophenolate Sodium and Cyclosporine: The Infinity Study Wed, 05 Mar 2014 00:00:00 +0000 In a six-month, multicenter, open-label trial, de novo kidney transplant recipients at low immunological risk were randomized to steroid avoidance or steroid withdrawal with IL-2 receptor antibody (IL-2RA) induction, enteric-coated mycophenolate sodium (EC-MPS: 2160 mg/day to week 6, 1440 mg/day thereafter), and cyclosporine. Results from a 30-month observational follow-up study are presented. Of 166 patients who completed the core study on treatment, 131 entered the follow-up study (70 steroid avoidance, 61 steroid withdrawal). The primary efficacy endpoint of treatment failure (clinical biopsy-proven acute rejection (BPAR) graft loss, death, or loss to follow-up) occurred in 21.4% (95% CI 11.8–31.0%) of steroid avoidance patients and 16.4% (95% CI 7.1–25.7%) of steroid withdrawal patients by month 36 (). BPAR had occurred in 20.0% and 11.5%, respectively (). The incidence of adverse events with a suspected relation to steroids during months 6–36 was 22.9% versus 37.1% (). By month 36, 32.4% and 51.7% of patients in the steroid avoidance and steroid withdrawal groups, respectively, were receiving oral steroids. In conclusion, IL-2RA induction with early intensified EC-MPS dosing and CNI therapy in de novo kidney transplant patients at low immunological risk may achieve similar three-year efficacy regardless of whether oral steroids are withheld for at least three months. A. Thierry, G. Mourad, M. Büchler, G. Choukroun, O. Toupance, N. Kamar, F. Villemain, Y. Le Meur, C. Legendre, P. Merville, M. Kessler, A.-E. Heng, B. Moulin, S. Queré, F. Di Giambattista, A. Lecuyer, and G. Touchard Copyright © 2014 A. Thierry et al. All rights reserved. The Role of mTOR Inhibitors in Liver Transplantation: Reviewing the Evidence Tue, 25 Feb 2014 14:19:35 +0000 Despite the success of liver transplantation, long-term complications remain, including de novo malignancies, metabolic syndrome, and the recurrence of hepatitis C virus (HCV) and hepatocellular carcinoma (HCC). The current mainstay of treatment, calcineurin inhibitors (CNIs), can also worsen posttransplant renal dysfunction, neurotoxicity, and diabetes. Clearly there is a need for better immunosuppressive agents that maintain similar rates of efficacy and renal function whilst minimizing adverse effects. The mammalian target of rapamycin (mTOR) inhibitors with a mechanism of action that is different from other immunosuppressive agents has the potential to address some of these issues. In this review we surveyed the literature for reports of the use of mTOR inhibitors in adult liver transplantation with respect to renal function, efficacy, safety, neurological symptoms, de novo tumors, and the recurrence of HCC and HCV. The results of our review indicate that mTOR inhibitors are associated with efficacy comparable to CNIs while having benefits on renal function in liver transplantation. We also consider newer dosing schedules that may limit side effects. Finally, we discuss evidence that mTOR inhibitors may have benefits in the oncology setting and in relation to HCV-related allograft fibrosis, metabolic syndrome, and neurotoxicity. Goran B. Klintmalm and Björn Nashan Copyright © 2014 Goran B. Klintmalm and Björn Nashan. All rights reserved. Alendronate as an Effective Treatment for Bone Loss and Vascular Calcification in Kidney Transplant Recipients Wed, 19 Feb 2014 07:56:28 +0000 Kidney transplant recipients develop secondary osteoporosis induced by immunosuppressive medication, with a high risk of fracture, and abdominal aortic calcification (AC) is a known predictor of cardiovascular mortality. In this study of 12 stable kidney recipients, we estimated the preventive effect of bisphosphonate treatment on bone loss and progression of AC. We randomly divided the subjects into a treatment group with alendronate (group A: 5 subjects) and a control group (group C: 7 subjects). Group A patients received 35 mg/week of alendronate over 24 months, while group C patients were not administered with any bisphosphonates. Two major endpoints were established: (1) the time-dependent change in bone mineral density (BMD) estimated with DEXA and (2) progression of abdominal AC, calculated twice as an index (ACI) using computed tomography data. Over the 2-year study period, group A patients showed significantly increased BMD of 1.86 ± 0.85% ( versus baseline), and almost complete inhibition of ACI progression (38.2 ± 24.2% to 39.6 ± 24.3%), but group C patients showed a decrease in BMD decline with bone loss and progression of ACI (32.8 ± 25.0% to 37.8 ± 29.2%, ). In conclusion, alendronate therapy was an effective treatment in kidney transplant recipients for secondary osteoporosis and vascular calcification as ectopic calcification. This clinical trial is registered with number JMA-IIA00155 of JMACCT CTR. Masanori Okamoto, Shintaro Yamanaka, Wataru Yoshimoto, and Takashi Shigematsu Copyright © 2014 Masanori Okamoto et al. All rights reserved. Donor-Recipient Size Mismatch in Paediatric Renal Transplantation Thu, 13 Feb 2014 12:45:05 +0000 Introduction. End stage renal failure in children is a rare but devastating condition, and kidney transplantation remains the only permanent treatment option. The aim of this review was to elucidate the broad surgical issues surrounding the mismatch in size of adult kidney donors to their paediatric recipients. Methods. A comprehensive literature search was undertaken on PubMed, MEDLINE, and Google Scholar for all relevant scientific articles published to date in English language. Manual search of the bibliographies was also performed to supplement the original search. Results. Size-matching kidneys for transplantation into children is not feasible due to limited organ availability from paediatric donors, resulting in prolonged waiting list times. Transplanting a comparatively large adult kidney into a child may lead to potential challenges related to the surgical incision and approach, vessel anastomoses, wound closure, postoperative cardiovascular stability, and age-correlated maturation of the graft. Conclusion. The transplantation of an adult kidney into a size mismatched paediatric recipient significantly reduces waiting times for surgery; however, it presents further challenges in terms of both the surgical procedure and the post-operative management of the patient’s physiological parameters. J. Donati-Bourne, H. W. Roberts, and R. A. Coleman Copyright © 2014 J. Donati-Bourne et al. All rights reserved.