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Among Asian countries, India has a vast potential to adopt a public bicycle-sharing system (PBSS) as a sustainable mode of transport after China. However, various barriers pose as hindrances in the implementation of PBSS in Indian urban areas. The primary objective of this paper is to identify and prioritise PBSS barriers, which inhibit the implementation of PBSS. For this study, a total of 31 barriers out of 41 reported barriers worldwide are shortlisted and ranked using the fuzzy analytic hierarchy process. A group of experts assisted in ranking the barriers by using a pair-wise comparison survey. The main contribution of this paper is to identify critical barriers and to rank them according to the Indian scenario. These findings can help practitioners, municipal engineers, urban planners and decision makers to formulate PBSS planning policy, which will overcome the PBSS implementation issues.

The demand for mobility is increasing day by day along with the rise in population. In the absence of clear guidelines and policy regarding the use of shared transport or Mass transportation, the use of personalized vehicles has grown rapidly. The personal vehicle owned individually, in which one cannot use others even belonging to the same family this leads to more traffic on the road. This leads to more consumption of fossil fuel and responsible for climate change. The Public Bicycle Sharing System (PBSS) is the concept, based on shared mobility in which users enable to use it for short-distance trips and drop it at any location through check-in/check-out operations without any accountability and likewise anyone can again use it with the same procedure. These multiple uses of the system conserve natural resources and increase the national economy by reducing the consumption of fossil fuel for mobility. The PBSS in urban areas, normally used for short-haul trips. However, by integrating it into public transport, the coverage of PT may also be increased, which attracts more users. In India implementation of this system is introduced in mid-2017 at Bhopal and within the short span, nearly 14 cities adopted PBSS in their urban areas. However, the majority of the system presently facing ridership issues due to the absence of bicycle-friendly infrastructure. Hence, it is essential to overcome such barriers using an appropriate facilitator. The BWM approach used in this study identifies the top facilitators based on the expert opinion survey to implement PBSS successfully. The result of this study shows that city infrastructure facilitators, technological facilitators, as well as a dedicated bicycle lane, government policy are the most effective facilitators which can improve the ridership and promote a circular economy through shared mobility. This study will help the decision-makers in developing the facilitator and enhance the ridership of PBSS.

Public bicycle sharing system (PBSS) has been adopted around the globe to reduce traffic congestion, CO2 emissions and for positive health effects. The first system was initially started in the year 1965 at Amsterdam and now it has been expanded almost in all the continents of the globe. The adoption of this concept was initially seen in developed countries. Now in the past decade various developing countries also have implemented the PBSS in their urban areas. However, the developing countries are facing many implementations and less ridership issues due to various barriers. This paper identifies the barriers which are hinders in the way of implementation of PBSS. An identified 31 barrier was categorized under six groups for ranking. The Fuzzy Analytical Hierarchical Process (FAHP) is applied to examine the relevance and prioritize them with the help of different stakeholders. Total 31 stakeholders were selected as experts from different working backgrounds for this study. The experts were grouped into six namely decision makers, academicians, consultants, scientists and researchers, operators, and users. The perspective of each group is also examined and checked using Kendall' coefficient. The majority of experts opine that City infrastructure barrier and travel characteristics barriers are most influential barriers for successful implementation of PBSS while technological and geographical barriers are least influential barriers. The overall results and opinions by different group of experts will help the decision makers to formulate effective policy to tackle all the barriers prior to implementation of PBSS in Indian urban areas. With the help of this framework, time and financial resources of the government can be utilized in an optimum way and the savings can be utilized for improving necessary city infrastructure.

In recent years cycling has seen a new beginning, triggered by the thrust towards greater environmental consciousness. In cities where cycling shares are low, efforts are being made to promote cycling as a viable mode of transport. As an emerging economy, Surat is now facing urban challenges that are more complex than Delhi and Mumbai especially in the central zone, CBD area of Surat. Due to congested streets and other limitations, it is not feasible for the provision of other transportation modes in the center area of it and for this reason city planners are planning for providing Public Bicycle Sharing System (PBSS) in Center zone. To understand factors starring to bike sharing adoption and hindrance to adoption, the IUTI-SVNIT Team conducted an intercept survey in the Central zone between January to March 2017. The HH survey reveals that about 75% two-wheeler users and 78% car users are willing to use PBSS if implemented. The results from analysis give an idea about if PBS system is launch then daily commuters, Pedestrian etc get benefits & willing to use this types of NMT facility in their daily trips. The study identify total 81 potential docking station with 1920 fleet size using maximum coverage area method and minimum impedance method in three phase in GIS environment. Author expect that practitioner and researchers will find study useful to overcome the various issues such as short-term parking problem, reducing vehicular congestion, increase livability etc. of dense urban areas.

In kidney transplantation, BK virus infection has historically resulted in high rates of graft dysfunction and graft loss. Unlike other opportunistic infections, no therapies have been shown to prevent BK. The purpose of the current study was to evaluate the safety and efficacy of ciprofloxacin for the prevention of BK viremia in kidney transplant recipients. Two hundred kidney transplant recipients were enrolled in a prospective, randomized, double-blind, placebo-controlled trial comparing a 3-month course of ciprofloxacin (n = 133) vs placebo (n = 67) for the prevention of BK viremia. The primary endpoint of BK viremia at month 6 posttransplant occurred in 25 (18.8%) patients in the ciprofloxacin group and 5 (7.5%) in the placebo group (P = .03). Higher rates of BK viremia (23.3% vs 11.9%; P = .06) and BK nephropathy (5.8% vs 1.5%; P = .26) remained at 12 months in the ciprofloxacin group. Ciprofloxacin use was associated with a significantly higher rate of fluoroquinolone-resistant gram-negative infections (83.3% vs 50%; P = .04). A 3-month course of ciprofloxacin was ineffective at preventing BK viremia in kidney transplant recipients and was associated with an increased risk of fluoroquinolone-resistant infections. Clinical trial registration number: NCT01789203.

BACKGROUND The pharmacokinetics and metabolism of tacrolimus, an immunosuppressant commonly used to prevent transplant rejection, can differ in specific subpopulations. This analysis examined treatment outcomes and safety of immediate-release tacrolimus (IR-Tac) and LCP-tacrolimus (LCPT) in stable Hispanic kidney transplant recipients. MATERIAL AND METHODS This was a post hoc analysis of clinical trial data from Hispanic adult stable kidney transplant recipients randomized to remain on IR-Tac or convert from IR-Tac to a reduced dose of LCPT (NCT00817206). Composite treatment failure was evaluated at 12 months. Estimated glomerular filtration rate and tacrolimus trough concentrations were evaluated over 12 months. RESULTS Fifty-five stable (LCPT n=26, IR-Tac n=29) kidney transplant recipients who self-identified as Hispanic or Latino were included in this analysis. Composite treatment failure occurred in 1 patient (4%) who converted to LCPT and 1 (3%) who remained on IR-Tac. The estimated glomerular filtration rate was stable over time and similar in the 2 treatment groups (P=0.08). Tacrolimus trough levels for both groups were similar over time in the 2 treatment groups (P=0.98). Treatment-emergent adverse events were similar in patients who converted to LCPT and in those who remained on IR-Tac. CONCLUSIONS Efficacy and safety were similar in Hispanic kidney transplant recipients who converted from IR-Tac to LCPT and in those remaining on IR-Tac.

Background Renal allograft survival is negatively affected by the development of de novo posttransplant donor-specific antibodies (dnDSA). We sought to determine whether treatment with intravenous immunoglobulin (IVIG) could remove or reduce the intensity of dnDSA. Methods A single-center study of 12 recipients with dnDSA and stable function who received IVIG 1 g/kg monthly for 6 months were compared with a contemporaneous cohort of 24 recipients with dnDSA who did not receive IVIG. Results The median time to first dnDSA was 6 months (interquartile range [IQR], 1-12), and follow-up was 83 months (IQR, 58-94) posttransplant. Resolution of dnDSA occurred in 27% of IVIG vs 46% of control recipients (P = .48). Fifty-eight percent of recipients in both cohorts demonstrated a reduction in the intensity of the dominant DSA at last follow-up (P =1.0). A reduction in the number of dnDSAs occurred in 58% vs 62% of the IVIG and control cohorts, respectively (P = .81). Post-dnDSA, acute rejection occurred in 8% of the IVIG vs 42% in the control group (P = .06). Forty-two percent of IVIG-treated vs 49% of control recipients had a deterioration in function from first dnDSA until most recent follow-up (P = .81). Actuarial graft survivals were equivalent between groups. Conclusions IVIG treatment of dnDSA in recipients with stable graft function had no impact on DSA clearance or MFI reduction, but this outcome may also be owing to sample size. Larger studies or alternate dosing regimens may be required to determine if there is any role for the use of IVIG as a treatment for dnDSA.

Supplemental Digital Content is available in the text., Objectives: Effective treatments for the critically ill patient with novel coronavirus disease 2019 are desperately needed. Given the role of cytokine release syndrome in the pathogenesis of coronavirus disease 2019-associated respiratory distress, therapies aimed at mitigating cytokine release, such as the interleukin-6 receptor-inhibiting monoclonal antibody tocilizumab, represent potential treatment strategies. Therefore, we examined the outcomes of critically ill coronavirus disease 2019 patients treated with tocilizumab and factors associated with clinical improvement. Design: A retrospective cohort analysis of 21-day outcomes for consecutive mechanically ventilated patients treated with tocilizumab from March 24, 2020, to May 4, 2020. Setting: Nine ICUs at six hospitals within a hospital system in Houston, Texas, United States. Patients: The first 62 coronavirus disease 2019 patients on invasive mechanical ventilation who were treated with tocilizumab, which was considered for all patients with severe disease. Interventions: Tocilizumab was administered either at a weight-based dose of 4–8 mg/kg or at a flat dose of 400 mg, with repeat administration in some patients at the physician’s discretion. Measurements and Main Results: The primary outcomes were mortality and clinical improvement, defined as extubation. By day 21 post-tocilizumab, clinical improvement occurred in 36 patients (58%) and 13 patients (21%) died. In both univariable and multivariable analyses, age less than 60 years was associated with clinical improvement. Transient transaminitis was the most common adverse reaction, occurring in 25 patients (40%). Conclusions: Based on clinical outcomes and mortality rates seen in previous reports of mechanically ventilated patients, tocilizumab, as part of the management strategy for severe coronavirus disease 2019, represents a promising option. These findings support the need for evaluation of tocilizumab in a randomized controlled trial.

Modern-day treatment regimens for human immunodeficiency virus (HIV) are not only highly effective, but are now more often available as convenient fixed-dose combination products. Furthermore, as medication adherence is of utmost importance in this setting, national guidelines endorse the use of such products. Transplant providers of HIV-infected patients will undoubtedly encounter these products, some of which contain medications known to drastically alter the metabolism of certain immunosuppressants. Herein, we describe an instance of drug interaction-induced calcineurin inhibitor (CNI) nephrotoxicity in a renal transplant recipient being started on a cobicistat-containing combination product for HIV. CNI toxicity, in turn, was resolved with the aid of phenytoin as an inducer of drug metabolism. This case underscores the importance of familiarity with newer combination products on the market and constant communication with HIV-positive transplant recipients and their providers.

Background. Acceptance of dual kidney transplantation (DKT) has proven difficult, due to surgical complexity and concerns regarding long-term outcomes. We herein present a standard technique for ipsilateral DKT and compare outcomes to single-kidney transplant (SKT) recipients.Methods. A retrospective single-center comparison of DKT and SKT performed between February 2007 and July 2013.Results. Of 516 deceased donor kidney transplants, 29 were DKT and 487 were SKT. Mean follow-up was 43 ± 67 months. DKT recipients were older and more likely than SKT recipients to receive an extended criteria graft (p<0.001). For DKT versus SKT, the rates of delayed graft function (10.3 versus 9.2%) and acute rejection (20.7 versus 22.4%) were equivalent (p= ns). A higher than expected urologic complication rate in the DKT cohort (14 versus 2%,p<0.01) was reduced through modification of the ureteral anastomosis. Graft survival was equivalent between DKT and SKT groups (p= ns) with actuarial 3-year DKT patient and graft survivals of 100% and 93%. At 3 years, the groups had similar renal function (p= ns).Conclusions. By utilizing extended criteria donor organs as DKT, the donor pool was enlarged while providing excellent patient and graft survival. The DKT urologic complication rate was reduced by modification of the ureteral anastomosis.

The present study discusses the historical overview of the Public bicycle sharing program from way back to its introduction in Amsterdam in the year 1965 to the present fourth-generation systems in developed and developing countries. In this paper, it is highlighted the various PBS system operated and popularly known for bringing radical changes in transportation systems. In India, due to smart city mission, most of the city has the PBS project. The analysis of the performance evaluation of existing PBS system and best practices definitely brings research insight for PBSS projects in India. This compendium of the research will help the planners and researchers to open the new avenue in the recent era of climate change also. At the concluding remark, this study analysis brings the interesting facts about the PBS system which one should know being a transport planner.

Background We sought to determine whether conversion from tacrolimus/mycophenolate mofetil (TAC-MMF) into tacrolimus/mTOR inhibitor (TAC-mTOR) immunosuppression would reduce the incidences of BK and CMV viremia after kidney/pancreas (KP) transplantation. Methods In this single-center review, the TAC-mTOR cohort (n = 39) was converted at 1 month post-transplant to an mTOR inhibitor and reduced-dose tacrolimus. Outcomes were compared to a cohort of KP recipients (n = 40) maintained on TAC-MMF. Results At 3 years post-transplant, KP survivals and incidences of kidney/pancreas rejection were equivalent between mTOR and MMF-treated cohorts. (P = ns). BK viremia-free survival was better for the mTOR vs MMF-treated group (P = .004). In multivariate analysis, MMF vs mTOR immunosuppression was an independent risk factor for BK viremia (hazard ratio 12.27, P = .02). Similarly, mTOR-treated recipients displayed better CMV infection-free survival compared to the MMF-treated cohort (P = .01). MMF vs mTOR immunosuppression (hazard ratio 18.77, P = .001) and older recipient age (hazard ratio 1.13 per year, P = .006) were independent risk factors for CMV viremia. Mean estimated GFR and HgbA1c levels were equivalent between groups at 1, 2, and 3 years post-transplantation. Conclusion Conversion from TAC/MMF into TAC/mTOR immunosuppression after KP transplantation reduced the incidences of BK and CMV viremia with an equivalent risk of acute rejection and similar renal/pancreas function.

Background De novo donor-specific antibodies (dnDSA) after renal transplant are associated with acute rejection (AR) and graft loss, yet most recipients with dnDSA have stable function and no AR. We assessed whether the persistence of dnDSA increased the risk of a detrimental outcome. Methods A single-center review of renal transplant recipients monitored for dnDSA at multiple time points post-transplant. An Isolated dnDSA was defined as one positive dnDSA and no additional positive tests, whereas ≥2 positive dnDSA was defined as persistent dnDSA. Results Of 708 recipients, 22% developed dnDSA, of whom 64% had persistent dnDSA. At median follow-up of 35 (range 12-74) months, there were fewer episodes of AR in the isolated dnDSA vs the persistent dnDSA group (2% vs 22%; P

BK polyomavirus infection and de novo donor-human leukocyte antigen (HLA) specific antibodies (dnDSA) are two well-known and distinct complications occurring after kidney transplantation. Recent literature suggests an association between the two events. This study aims to examine the relationship between BK viremia (BKV) and dnDSA and to identify potential risk factors for dnDSA following BKV in kidney transplant recipients. A retrospective review of 1019 recipients from Houston Methodist Hospital was conducted. All patients underwent routine screening for BKV and dnDSA. Median follow-up was 44 months. BKV was detected in 186 (18%) patients at a median of 107 (82-205) days post-transplant. dnDSA occurred in 283 (28%) patients at a median of 272 (62-575) days post-transplant. Of the 69 dnDSA-positive/BKV-positive patients, dnDSA detection occurred after BKV onset in 46 patients. Thus, 46 (28%) previously DSA-negative patients later became dnDSA-positive following BKV, not significantly different from the rate seen in BKV-negative patients (26%; p=0.5). Median time to DSA detection following BKV onset was 232 days (interquartile range, 119-460) post-BKV detection. Multivariate analysis revealed a greater number of HLA mismatches and viral clearance as risk factors for development of dnDSA following BKV, whereas delayed graft function was associated with a lower risk of dnDSA. In conclusion, despite being considered a result of over-immunosuppression, BKV can still be followed by dnDSA in a substantial proportion of patients. Monitoring for dnDSA in patients being managed for BKV may be warranted.

BACKGROUND This study reviewed the outcomes of a screening protocol for BK viremia to determine if early diagnosis, followed by immunosuppression minimization, would prevent progression to nephropathy and graft loss. METHODS This review included 369 renal transplant recipients tested for BK virus at serial time points after transplantation. Management included immunosuppression minimization plus cidofovir treatment for BK nephropathy. RESULTS Recipients received tacrolimus-based immunosuppression, with 8% prednisone-free and 6% who received desensitization. With a mean follow-up of 22 ± 10 months, 16% (n = 57) of recipients became BK viremia positive. The median (range) time to diagnosis was 3 (1-17) months. Because renal biopsy was performed selectively, 59% of recipients underwent biopsy, with 47% showing BK nephropathy. Seventy-four percent of recipients cleared the virus at a median (range) time of 9 (3-33) months, with four grafts lost to BK nephropathy. Cidofovir-treated recipients displayed a higher viral load at diagnosis but showed equivalent renal function at last evaluation. In multivariate analysis, recipient age, Asian ethnicity, deceased donor, and prednisone use were factors independently associated with BK viremia. Actuarial survival of BK-positive grafts was worse than that of BK-negative grafts (P

Lymphocyte-depleting induction lowers acute rejection (AR) rates among high-immunologic risk (HIR) renal transplant recipients, including African Americans (AAs), retransplants, and the sensitized. It is unclear whether different HIR subgroups experience similarly low rates of AR. We aimed to describe the incidence of AR and de novo donor-specific antibody (dnDSA) among HIR recipients categorized by age, race, or donor type. All received antithymocyte globulin (ATG) induction and triple maintenance immunosuppression. A total of 464 HIR recipients from 2007 to 2014 were reviewed. AR and dnDSA rates at 1 year for the entire population were 14% and 27%, respectively. AR ranged from 6.7% among living donor (LD) recipients to 30% in younger AA deceased donor (DD) recipients. De novo donor-specific antibody at 1 year ranged from 7% in older non-AA LD recipients to 32% in AAs. AA race remained as an independent risk factor for AR among DD recipients and for dnDSA among all HIR recipients. Development of both AR and dnDSA within the first year was associated with a 54% graft survival at 5 years and was an independent risk factor for graft loss. Despite utilization of recommended immunosuppression for HIR recipients, substantial disparities exist among subgroups, warranting further consideration of individualized immunosuppression in certain HIR subgroups.

Increasing evidence suggests a detrimental effect of donor-specific antibodies directed against the human leukocyte antigen (HLA)-A, -B, and -DR loci on renal allograft outcomes. Limited data exist on the impact of de novo HLA-DQ antibodies. Over a 3-year period, we prospectively monitored 347 renal transplant recipients without pre-transplant donor-specific antibodies for their development de novo . After 26 months of follow-up, 62 patients developed donor-specific antibodies, of which 48 had a HLA-DQ antibody either alone (33 patients) or in combination with an HLA-A, -B, or -DR antibody (15 patients). Only 14 patients developed a donor-specific HLA-A, -B, or -DR antibody without a HLA-DQ antibody present. Acute rejection occurred in 21% of the HLA-DQ–only patients, insignificant when compared with 11% of patients without donor-specific antibodies. At the last follow-up, the mean serum creatinine and the fraction of patients with proteinuria were significantly higher in those that developed only HLA-DQ than those without antibodies. The 3-year graft survival was significantly worse when HLA-DQ antibodies were combined with non-DQ antibodies (52%) compared with HLA-DQ alone, non-DQ antibodies alone, or no antibodies (92–94%). Thus, our prospective monitoring study found that donor-specific HLA-DQ antibodies were the most common type detected and these antibodies may contribute to inferior graft outcomes. Ongoing surveillance is necessary to determine the long-term outcome of patients developing HLA-DQ donor-specific antibodies.

Gainer SM, Patel SJ, Seethamraju H, Moore LW, Knight RJ, Gaber AO. Increased mortality of solid organ transplant recipients with H1N1 infection: a single center experience. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01443.x. © 2011 John Wiley & Sons A/S. Abstract: Immunosuppressed solid organ transplant recipients are included in the cohort at increased risk for complications of viral infections such as the newly encountered H1N1. A retrospective review was performed to collect data on patients hospitalized during a recent H1N1 epidemic. H1N1 was suspected based on symptoms and real-time reverse-transcriptase-polymerase-chain-reaction assay confirmed the diagnosis. From August through October of 2009, 89 patients were admitted to The Methodist Hospital, Houston, Texas, with H1N1. Eighteen were solid organ transplant recipients with an age range of 34–69 yr. This group included nine kidney, five lung, one kidney-pancreas, one liver, and two heart recipients. Severe cardiac or pulmonary comorbidities existed in over half of non-transplant patients, while only eight of these non-transplant patients were otherwise healthy. Eighty-nine percent of transplant patients presented with fever or chills, 72% with cough, and 56% with gastrointestinal distress. Symptoms were similar to non-transplant patients. All transplant patients were treated with oseltamivir. Two non-transplant patients and three transplant patients died. Thirty-day survival was 97% in non-transplant and 83% in transplant patients (p = 0.02). In the context of an initial epidemic of H1N1, infection was associated with increased risk of complications and mortality in solid organ transplant recipients.

Patel SJ, Knight RJ, Suki WN, Abdellatif A, Duhart BT, Krauss AG, Mannan S, Nezakatgoo N, Gaber AO. Rabbit antithymocyte induction and dosing in deceased donor renal transplant recipients over 60 yr of age. Clin Transplant 2011: 25: E250–E256. © 2011 John Wiley & Sons A/S. Abstract: Background: Antithymocyte globulin (rATG) is a commonly used induction agent in renal transplantation; however, data in older kidney recipients are limited. Methods: We reviewed charts of 301 deceased donor renal transplants who received a protocol consisting of 3–7 doses of rATG and triple maintenance therapy. Outcomes of patients >60 yr of age (n = 45) were compared to those aged 18–59 yr (n = 256). Results: Older recipients had more diabetics, were more likely to receive expanded criteria donor kidneys (p 60 received less cumulative rATG (4.6 vs. 5.1 mg/kg; p 60 group (2% vs. 16%, p 60 group at three yr was lower (80% vs. 95%; p = 0.02). Specifically, patients >60 with delayed graft function and rATG cumulative dosing >6 mg/kg had a survival of 6 mg/kg. These data suggest that when used, lower cumulative dosages of rATG are preferable in the older recipient.

Dawson KL, Patel SJ, Putney D, Suki WN, Gaber AO. Cardioprotective medication use after renal transplantation. Clin Transplant 2010: 24: E253–E256. © 2010 John Wiley & Sons A/S. Abstract: Cardiovascular disease is the leading cause of death in renal transplant patients. This study compares the use of cardioprotective medications in adult kidney transplant recipients at a single center with recommendations, which have been validated in the general population. Cardioprotective medication use was retrospectively collected post-renal transplant. Patients were defined as high risk if they had pre-transplant coronary heart disease or equivalent risk. “Optimal” treatment was defined as a patient receiving aspirin, statin, angiotensin-converting enzyme inhibitors/angiotensin receptor blocker, and a beta-blocker according to cardiovascular risk. The percentage of high-risk patients optimally treated at one, three, six, and 12 months was 7.7%, 11.5%, 17.6%, and 18.8%, respectively. Although the use of cardioprotective medications was evident in transplant recipients, opportunities exist to increase the use of optimal cardioprotective regimens after renal transplantation.

Aims: Tacrolimus has a narrow therapeutic window and shows significant interindividual difference in dose requirement. In this study we aim to first identify genetic factors that impact tacrolimus dose using a candidate gene association approach, and then generate a personalized algorithm combining identified genetic and clinical factors to predict individualized tacrolimus dose. Materials & methods: We screened 768 SNPs in 15 candidate genes in metabolism, transport and calcineurin inhibition pathways of tacrolimus, for association with tacrolimus dose in a discovery cohort of 96 patients. Results: Four polymorphisms in CYP3A5 and one polymorphism in CYP3A4 were identified to be significantly associated with tacrolimus stable dose (p < 8.46 × 10-5). The same SNPs were identified when dose-normalized trough tacrolimus concentration was analyzed. The CYP3A5*1 allele was associated with significantly higher stable dose, bigger dose increase, higher risk of being underdosed and lower incidence of post-transplant hyperlipidemia. ABCB1 polymorphisms were not associated with stable dose. No significant difference was found between CYP3A5 expressers and nonexpressers in incidence of acute rejection and time to first rejection. Age, ethnicity and CYP3A inhibitor use could predict 30% of tacrolimus dosing variability. Adding the identified genetic polymorphisms to the algorithm increased the predictability to 58%. In two validation cohorts of 77 and 64 patients, the algorithm containing both genetic and clinical factors produced correlation coefficients of 0.63 and 0.42, respectively. This algorithm gave a prediction of the stable doses closer to the actual doses when compared with another algorithm based only on the CYP3A5 genotype. Conclusion: CYP3A5 genotype is the most significant genetic factor that impacts tacrolimus dose among the genes studied. This study generated the first pharmacogenomics model that predicts tacrolimus stable dose based on age, ethnicity, genotype and comedication use. Our results highlight the importance of incorporating both genetic and clinical, demographic factors into dose prediction.

Background Fever occurs frequently early after pancreas transplant, however, the exact cause is often undetermined. Limited data are available on pancreas recipients experiencing unexplained, noninfectious fever. This study aims to characterize unexplained fever (UF) in pancreas recipients and its effect on patient and graft outcomes. Methods We performed a retrospective cohort study of UF among consecutive pancreas or simultaneous pancreas-kidney transplant recipients from 1 January 2011 to 31 August 2015. Classification of UF was based on the absence of positive cultures, radiologic findings, and other diagnostic features of infection or rejection. Results Twenty-three of 92 (25%) patients experienced UF. The UF episode first occurred at a mean of 31 ± 17 days post-transplant and accounted for 34 admissions with an average length of stay of 5.1 ± 3.4 days. Intravenous corticosteroid was administered following confirmation of negative diagnostic tests in 77% of patients, with fever resolution occurring in all. No differences were seen in rates of biopsy-proven rejection, graft loss, death, or documented infections compared to UF-free patients during the first-year post-transplant. Conclusion UF is a common cause for readmission following pancreas transplantation. While the etiology of UF remains difficult to identify, UF occurrence was not associated with adverse outcomes during the first-year post-transplant.

Although current therapies for pretransplant desensitization and treatment of antibody-mediated rejection (AMR) have had some success, they do not specifically deplete plasma cells that produce antihuman leukocyte antigen (HLA) antibodies. Bortezomib, a proteasome inhibitor approved for the treatment of multiple myeloma (a plasma cell neoplasm), induces plasma cell apoptosis. In this paper we review the current body of literature regarding the use of this biological agent in the field of transplantation. Although limited experience with bortezomib may seem to show promise in the realm of transplant recipients desensitization and treatment of AMR, there is also experience that may suggest otherwise. Bortezomib's role in desensitization protocols and treatment of AMR will be defined better as more clinical data and trials become available.

Sirolimus is an antiproliferative immunosuppressive agent that inhibits the mammalian target of rapamycin. It is highly effective in preventing acute renal allograft rejection and can be used with either calcineurin inhibitors, antimetabolites or corticosteroids. Early studies in renal transplantation have provided insight into optimal dosing strategies of sirolimus and of concomitant immunosuppressive agents. Familiarity with the adverse effect profile of sirolimus and pharmacokinetic and dynamic interactions with other immunosuppressive agents allows for earlier recognition and better management of sirolimus-related complications. The role of sirolimus in preserving long-term renal function, post-transplant malignancies and in prevention of atherosclerosis is currently being considered.

Background. Induction rabbit antithymocyte globulin (rATG) is largely used in renal allograft recipients at risk for delayed graft function (DGF) and immunologic rejection. The purpose of our study was to characterize risk factors and outcomes associated with DGF when it occurs in recipients undergoing routine rATG induction. Methods. We retrospectively reviewed our experience in a predominantly high-risk population receiving modern immunosuppressive regimens. Results. Of 231 deceased-donor transplants, high-risk characteristics included African American race (68%), retransplants (12%), peak panel reactive antibody of atleast 20% (19%), expanded criteria donor kidney (15%), and cold ischemia time exceeding 24 hr (27%). DGF occurred in 29% of patients. rATG was continued to a dose of 7.3 mg/kg in DGF patients and 5 mg/kg in non-DGF patients (P

Aspergillus infection remains a significant and deadly complication after liver transplantation (LT). We sought to determine whether the antifungal prophylactic use of voriconazole reduces the incidence of invasive aspergillosis (IA) in high-risk LT recipients without prohibitively increasing cost. During the study era (April 2008 to April 2014), 339 deceased donor LTs were performed. Of those patients, 174 high-risk recipients were administered antifungal prophylaxis with voriconazole. The median biological Model for End-Stage Liver Disease score at the time of LT was 33 (range, 18-49) with 56% requiring continuous renal replacement therapy and 50% requiring ventilatory support immediately before transplantation. Diagnosis of IA was stratified as proven, probable, or possible according to previously published definitions. No IA was documented in patients receiving voriconazole prophylaxis. At 90 days after LT, the institutional cost of prophylaxis was $5324 or 5.6% of the predicted cost associated with post-LT aspergillosis. There was no documentation of resistant strains isolated from any recipient who received voriconazole. In conclusion, these data suggest that voriconazole prophylaxis is safe, clinically effective, and cost-effective in high-risk LT recipients.

Herein, we describe a case of early belatacept conversion in a human immunodeficiency virus (HIV)-positive kidney transplant recipient in an effort to improve suboptimal graft function and avoid drug interactions following anti-thymocyte globulin (ATG) administration. We observed improvement in renal function without HIV disease progression or opportunistic infections. Donor-specific antibodies appeared shortly after conversion but cleared without intervention. This case highlights belatacept as a means to improve renal function and avoid significant drug interactions even following ATG induction.

Background. Preemptive transplantation results in excellent patient and graft survival yet most transplant candidates are referred for transplantation after initiation of dialysis. The goal of this study was to determine barriers to preemptive renal transplantation. Methods. A nonvalidated questionnaire was administered to prospective kidney transplant recipients to determine factors that hindered or favored referral for transplantation before the initiation of dialysis. Results. One hundred ninety-seven subjects referred for a primary renal transplant completed the questionnaire. Ninety-one subjects (46%) had been informed of preemptive transplantation before referral, and 80 (41%) were predialysis at the time of evaluation. The median time from diagnosis of renal disease to referral was 60 months (range, 2Y444 months). In bivariate analysis, among other factors, knowledge of preemptive transplantation was highly associated (odds ratio=94.69) with referral before initiation of dialysis. Given the strong association between knowledge of preemptive transplantation and predialysis referral, this variable was not included in the multivariate analysis. Using multivariate logistic regression analysis, white recipient race, referral by a transplant nephrologist, recipient employment, and the diagnosis of polycystic kidney disease were significantly associated with presentation to the pretransplant clinic before initiation of dialysis. Conclusion. The principle barrier to renal transplantation referral before dialysis was patient education regarding the option of preemptive transplantation. Factors significantly associated with referral before dialysis were the diagnosis of polycystic kidney disease, white recipient race, referral by a transplant nephrologist, and employed status. Greater effort should be applied to patient education regarding preemptive transplantation early after the diagnosis of end-stage renal disease.

Background In renal transplantation, BK virus infection can result in significant graft nephropathy and loss. While reduction in immunosuppression (IS) is considered standard therapy, adjunct agents may be warranted. Data are suggestive of a possible role of cidofovir for the management of BK. This study aims to describe the course of BK viremia (BKV) in a large cohort of renal transplant patients receiving adjunct cidofovir. Methods We evaluated kidney and kidney-pancreas recipients who received cidofovir combined with reduced IS for management of high-level BKV or BK virus nephropathy (BKVN). We examined the rate and timing of BKV clearance, and performed a multivariate analysis to identify risk factors associated with long-term (>6 months) viremia. Results In total, 75 patients received a median of 13 doses of cidofovir in conjunction with reduced IS; 32 patients (43%) had short-term BKV (≤6 months), and 43 (57%) had long-term BKV. Overall, 53 of 75 patients (71%) eventually cleared BKV at a median of 4.2 months (interquartile range 2.1–9.3 months). Independent factors associated with long-term BKV included older age (odds ratio [OR] 1.1, P = 0.02), delayed graft function (OR 31.4, P = 0.01), and higher peak BKV (OR 12.8, P = 0.02), while BKV reduction by at least 1 log10copies/mL at 1 month of treatment was associated with clearance within 6 months (OR 49.3, P

Background. Renal transplant recipients with de novo DSA (dDSA) experience higher rates of rejection and worse graft survival than dDSA-free recipients. This study presents a single-center review of dDSA monitoring in a large, multi-ethnic cohort of renal transplant recipients. Methods. The authors performed a nested case-control study of adult kidney and kidney-pancreas recipients from July 2007 through July 2011. Cases were defined as dDSA-positive whereas controls were all DSA-negative transplant recipients. DSA were determined at 1, 3, 6, 9, and 12 months posttransplant, and every 6 months thereafter. Results. Of 503 recipients in the analysis, 24% developed a dDSA, of whom 73% had dDSA against DQ antigen. Median time to dDSA was 6.1 months (range 0.2Y44.6 months). After multivariate analysis, African American race, kidney-pancreas recipient, and increasing numbers of human leukocyte antigen mismatches were independent risk factors for dDSA. Recipients with dDSA were more likely to suffer an acute rejection (AR) (35% vs. 10%, PG0.001), an antibody-mediated AR (16% vs. 0.3%, PG0.001), an AR ascribed to noncompliance (8% vs. 2%, P=0.001), and a recurrent AR (6% vs. 1%, P=0.002) than dDSA-negative recipients. At a median follow-up of 31 months, the deathcensored actuarial graft survival of dDSA recipients was worse than the DSA-free cohort (P=0.002). Yet, for AR-free recipients, there was no difference in graft survival between cohorts (P=0.66). Conclusions. Development of dDSA was associated with an increased incidence of graft loss, yet the detrimental effect of dDSA was limited in the intermediate term to recipients with AR.

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.

The response to allografting involves adaptive and innate immune mechanisms. In the adaptive system, activated T cells differentiate to cytotoxic effectors that attack the graft and trigger B cells to differentiation to plasma cells that produce anti-HLA antibodies. The innate immune system recognizes antigens in a non-specific manner and recruits immune cells to the graft through the productions of chemotactic factors, and activation of cytokines and the complement cascade. In the kidney the tubules and the endothelium are the targets of the rejection response. Immune suppression is effective in modulating the adaptive immune system effect on graft histology.

Anti-Xa monitoring for low molecular weight heparin (LMWH) is currently recommended in obese, renally impaired, and pregnant patients. Substantial evidence indicates that solid organ transplant (SOT) patients are at an increased risk of renal impairment, thus representing a population at risk of LMWH accumulation. The purpose of this study was to review our experience with LMWH dosing and monitoring in a cohort of transplant recipients. This was a retrospective, single-center review of 96 SOT patients receiving enoxaparin treatment and anti-Xa monitoring. The percent of patients with supratherapeutic anti-Xas (>1 IU/mL) was determined, as was the relationship between enoxaparin dosages and anti-Xa levels and bleeding. The cohort had a mean age of 62 yr and creatinine clearance of 59 mL/min and was primarily lung transplant recipients (73%). The mean enoxaparin dose was 0.82 mg/kg, which resulted in a mean anti-Xa level of 0.98 IU/mL. Despite the reduced enoxaparin dose, 44% of patients experienced a supratherapeutic anti-Xa level. Patients with supratherapeutic anti-Xas had higher doses than those within the therapeutic range (0.89 mg/kg vs. 0.77 mg/kg; p = 0.002). No major bleeds occurred. Supratherapeutic anti-Xa levels are common in transplant patients receiving enoxaparin therapy. Empirically reduced dosing of enoxaparin and monitoring may warrant consideration in this population.

The pharmacokinetics of tacrolimus are influenced by many factors, including genetic variability, acute infections, liver dysfunction, and interacting medications, which can result in elevated concentrations. The most appropriate management of acute tacrolimus toxicity has not been defined though case reports exist describing the therapeutic use of enzyme inducers to increase tacrolimus metabolism and decrease concentrations. We are reporting on the utilization of phenytoin to assist in decreasing tacrolimus concentrations in a case series of four solid organ transplant recipients with acute, symptomatic tacrolimus toxicity presenting with elevated serum creatinine, potassium, and tacrolimus trough concentrations greater than 30 ng/mL. All four patients had the potential causative agents stopped or temporarily held and were given 300 to 400 mg/day of phenytoin for two to three days. Within three days of beginning phenytoin, all four patients had a decrease in tacrolimus concentration to less than 15 ng/mL, a return to or near baseline creatinine concentration, and lack of phenytoin-related side effects. Therefore, phenytoin appears to be a safe and potentially beneficial treatment option in patients with symptomatic tacrolimus toxicity.

Introduction Management of renal transplant recipients with a negative complement-dependent cytotoxicity-antihuman globulin (CDC-AHG) cross-match and pretransplant donor-specific antibody (DSA) is controversial. We sought to compare outcomes of immunologically high-risk living donor (LD) renal transplant recipients with and without DSA. Methods We conducted a single-center, retrospective review of all high immune-risk LD renal transplant recipients with a negative CDC-AHG cross-match performed between January 2008 and December 2010. Pretransplant desensitization for DSA was not utilized. Immunosuppression consisted of thymoglobulin induction, followed by tacrolimus, myeophenolate mofetil, and prednisone. DSA was assessed pretransplant and at 1, 3, 6, 9, and 12 months, and every 6 months thereafter. Results Between January 2008 and December 2010, 44 LD renal transplants were performed in high immune-risk recipients with a negative CDC-AHG cross-match. Outcomes of 14 recipients with pretransplant DSA were compared with 30 recipients with no DSA. After a median follow-up of 26 months (range, 12–40), overall death-censored graft survival was 100%, with no acute rejection episodes in the DSA group and 1 antibody-mediated rejection in the non-DSA cohort. Mean serum creatinines of the DSA and non-DSA groups at 1 year post-transplant were 1.0 ± 0.4 and 1.2 ± 0.6 mg/dL (P = NS), respectively. Among the pretransplant DSA cohort, 5 of the 14 (36%) developed persistent post-transplant DSA at a median of 9 months (range, 3–24) versus 2 of 30 (7%; P = .025) at a median of 12 months post-transplant in the non-DSA cohort. All recipients in the pretransplant DSA group underwent renal biopsy for persistent post-transplant DSA. Three of 5 biopsies showed C4D deposition in peritubular capillaries without glomerulopathy or arteriopathy. Conclusions Early post-transplant outcomes for LD recipients with a negative cross-match and pretransplant DSA were excellent. In recipients with good and stable renal function, the significance of persistent post-transplant DSA in combination with C4D deposition on biopsy is unclear at this time.

Immunosuppressed solid organ transplant recipients are included in the cohort at increased risk for complications of viral infections such as the newly encountered H1N1. A retrospective review was performed to collect data on patients hospitalized during a recent H1N1 epidemic. H1N1 was suspected based on symptoms and real-time reverse-transcriptase-polymerase-chain-reaction assay confirmed the diagnosis. From August through October of 2009, 89 patients were admitted to The Methodist Hospital, Houston, Texas, with H1N1. Eighteen were solid organ transplant recipients with an age range of 34-69 yr. This group included nine kidney, five lung, one kidney-pancreas, one liver, and two heart recipients. Severe cardiac or pulmonary comorbidities existed in over half of non-transplant patients, while only eight of these non-transplant patients were otherwise healthy. Eighty-nine percent of transplant patients presented with fever or chills, 72% with cough, and 56% with gastrointestinal distress. Symptoms were similar to non-transplant patients. All transplant patients were treated with oseltamivir. Two non-transplant patients and three transplant patients died. Thirty-day survival was 97% in non-transplant and 83% in transplant patients (p=0.02). In the context of an initial epidemic of H1N1, infection was associated with increased risk of complications and mortality in solid organ transplant recipients.

BACKGROUND Previously transplanted patients are more likely to be sensitized, leading to prolonged waitlist times and decreased graft survival. This analysis of the United Network for Organ Sharing kidney/pancreas transplant database investigates factors at the time of first transplant associated with increased sensitization in patients undergoing second transplantation. METHODS Records of nonsensitized patients (panel reactive antibodies [PRA]

Antithymocyte globulin (rATG) is a commonly used induction agent in renal transplantation; however, data in older kidney recipients are limited.We reviewed charts of 301 deceased donor renal transplants who received a protocol consisting of 3-7 doses of rATG and triple maintenance therapy. Outcomes of patients60 yr of age (n = 45) were compared to those aged 18-59 yr (n = 256). Older recipients had more diabetics, were more likely to receive expanded criteria donor kidneys (p0.01), and over 30% were sensitized. Recipients60 received less cumulative rATG (4.6 vs. 5.1 mg/kg; p0.01). Three-yr acute rejection was lower in the60 group (2% vs. 16%, p0.01) although glomerular filtration rates were similar between groups. Actuarial graft survival was similar; however, patient survival in the60 group at three yr was lower (80% vs. 95%; p = 0.02). Specifically, patients60 with delayed graft function and rATG cumulative dosing6 mg/kg had a survival of50% by two yr.Recipients over 60 yr receiving rATG induction have acceptable renal function and a low risk of rejection; however, reduced survival was noted among those receiving6 mg/kg. These data suggest that when used, lower cumulative dosages of rATG are preferable in the older recipient.