Number Of Acute Rejection Episodes Research Articles

Donor Simvastatin Treatment is More Effective in Donors with Low Plasma Levels of Arginine

<h3>Purpose</h3> Brain death may lead to a severe impairment of endothelial function and affect graft function. Recent study shows that simvastatin treatment to the organ donor decreases plasma biomarker levels of myocardial injury and heart failure and reduces the number of acute rejection episodes with hemodynamic compromise early after heart transplantation. However, the mechanisms of donor simvastatin treatment remain unknown. Therefore, we analyzed the plasma metabolomics of brain-dead heart transplant donors with or without simvastatin treatment to examine the molecular background of the beneficial effects. <h3>Methods</h3> In a prospective, double-blinded randomized controlled trial, 84 multiorgan donors were randomly assigned to receive either 80 mg of simvastatin (n=42) via nasogastric tube or to receive no simvastatin (n=42). Plasma samples from 84 human brain-dead multi-organ donors were collected immediately before organ procurement. We profiled over 100 targeted metabolites using mass spectrometry. <h3>Results</h3> We found that arginine and tryptophan were weakly negatively correlated with simvastatin treatment. Univariate Cox regression analysis showed that low levels of arginine were significantly associated with acute rejection and graft-related mortality (Figure 1 A,B). Additionally, we saw that donor simvastatin treatment significantly reduced the number of acute rejections by 41% (p=0.012) in low arginine group within the first year (Figure 1C). There was no difference in donor demographics between the groups. However, there was a statistically significantly higher need for mechanical circulatory support for hearts from donors with low arginine levels. <h3>Conclusion</h3> This study shows that donor simvastatin treatment could be more efficient in brain-dead heart transplant donors with low arginine. Further analysis will be conducted by exploring the interplay between arginine and simvastatin in detail. The complete results will be presented at the ISHLT2022 congress.

Variable selection for longitudinal zero-inflated power series transition model

ABSTRACT In modeling many longitudinal count clinical studies, the excess of zeros is a common problem. To take into account the extra zeros, the zero-inflated power series (ZIPS) models have been applied. These models assume a latent mixture model consisting of a count component and a degenerated zero component that has a unit point mass at zero. Usually, the current response measurement in a longitudinal sequence is a function of previous outcomes. For example, in a study about acute renal allograft rejection, the number of acute rejection episodes for a patient in current time is a function of this outcome at previous follow-up times. In this paper, we consider a transition model for accounting the dependence of current outcome on the previous outcomes in the presence of excess zeros. New variable selection methods for the ZIPS transition model using least absolute shrinkage and selection operator (LASSO), minimax concave penalty (MCP) and smoothly clipped absolute deviation (SCAD) penalties are proposed. An expectation-maximization (EM) algorithm using the penalized likelihood is applied for both parameters estimations and conducting variable selection. Some simulation studies are performed to investigate the performance of the proposed approach and the approach is applied to analyze a real dataset.

MO012IS IT SAFE TO USE INTERLEUKIN-2 RECEPTOR ANTAGONIST INDUCTION THERAPY IN 2DR MISMATCH RENAL TRANSPLANTS IN TACROLIMUS ERA?

Abstract Background and Aims 2DR HLA mismatch indicates high immunological risk renal transplant. Induction therapy with rabbit Anti-thymocyte Globulin (r-ATG) and IL-2 Receptor Antagonist (IL-2RA) resulted in marked reduction of acute allograft rejection rate and improved graft survival. However, the outcomes in 2DR (HLA-DR) mismatched renal transplant recipients (RTRs) in the era tacrolimus-mycophenolate mofetil maintenance immunosuppression remains understudied. Method Using data from the United States organ procurement and transplantation network, all 2 DR mismatched RTRs with panel reactive antibodies &amp;lt;20% maintained on tacrolimus and mycophenolate mofetil immunotherapy between 2000 and 2017 were retrospectively reviewed. Data including age, sex, gender, ethnicity, functional status, diabetes, body mass index, cold ischemia time, number of previous transplants, panel reactive antibodies, donor type, donor age, HLA-mismatches, number of acute rejection episodes, induction therapies, maintenance immunotherapy, recipients and graft survival were collected. Based on induction therapies administered, RTRs were divided into 2 groups: (r-ATG) and IL-2RA groups. Poisson regression analysis was used to assess effect of induction therapies on acute rejection episodes. Cox hazard regression analysis was used to assess effect of different induction therapies on patient and graft survival Results 3379 patients received IL2-RA while 3677 patients received ATG for induction. There were no significant differences between both groups in terms of acute rejection episodes (95% CI ranges from 0.95 to 1.068, P=0.805), graft survival (95% CI: 0.91 - 1.06, P=0.712), or patient survival (95% CI: -0.949 - 1.12, P=0.43) . Conclusion This study revealed no significant difference in acute rejection episodes, patient or graft survival when utilizing ATG vs IL-2RA in 2DR HLA mismatched renal transplant recipients with PRA&amp;lt;20%, in the tacrolimus-based maintenance immunosuppression era. Therefore, IL2-RA is a safe induction therapy in this group of patients and non-inferior to –ATG induction therapy.

P1632IMPACT OF RENAL TRANSPLANTATION ON THE FUNCTIONAL STATUS OF PATIENTS WITH END-STAGE RENAL FAILURE IN TACROLIMUS ERA

Abstract Background and Aims Survival after renal transplantation has improved significantly over the past 20 years. On the contrary, surprisingly little is known about the functional status post-transplant. A fundamental understanding of the functional status of patients surviving renal transplantation is of primary importance to clinicians and families alike, who often pursue renal transplantation with a principal hope that functional status will improve. The aim of our study is to assess the effect of renal transplantation on functional status of the patients in tacrolimus era Method Using data from the United States organ procurement and transplantation network, all renal transplant patients maintained on tacrolimus-based immunotherapy and had functional assessment at time of transplant and five-years post-transplant were retrospectively reviewed. Data including age, sex, gender, ethnicity, functional status, diabetes, body mass index, cold ischemia time, number of previous transplants, panel reactive antibodies, donor type, donor age, HLA-mismatches, number of acute rejection episodes, induction therapies, maintenance immunotherapy on discharge were collected. Functional status was defined according to Karnofsky score measurements. Descriptive analysis was used to assess effect of renal transplantation on functional status. Outcome measured was functional status five-years post-transplant. Multiple logistic regression analysis was used to assess factors affecting functional status post-transplant. Results 19704 patients were included in the study. Among patients with mild impairment at time of transplant, only 13.55% showed worsening of functional status. Among patients with moderate impairment at time of transplant, 65.5% showed improvement of functional status while only 3.92% showed worsening of functional status. Among patients with severe impairment at time of transplant, 88.56% showed improvement in functional status (64.57% showed improvement to mild impairment and 23.99% showed improvement to moderate impairment). Multiple logistic regression analysis showed that steroid withdrawal protocol is associated with improvement in functional status (OR=1.24, P=0.007, CI ranges from 1.06 to 1.45), while dialysis maintenance before transplantation was associated with abnormal functional status post-transplant (OR=0.73, P=0.003, CI ranges from 0.59 to 0.89). Conclusion This study revealed that renal transplantation is associated with substantial improvement in functional status of the patients. Steroid withdrawal protocols is associated with significant improvement in functional status while maintenance dialysis before transplantation is associated with worse outcomes. This study recommends using steroid withdrawal protocols and performing transplantation for the patients at the pre-dialysis state. Functional status at time of transplant shouldn’t be a hindrance to performing transplantation.

Burden of Infectious Complications after Upper Extremity Allotransplantation

Introduction Risk-to-benefit ratio of upper extremity allotransplantation (UEA), a non-vital transplantation procedure, remains to be clarified, as concerns have been raised regarding infectious, metabolic and malignant complications of lifelong immunosuppression. The aim of this study was to provide a relevant assessment of the infectious risk in UEA recipients. Infectious complications in UEA recipients were analyzed and compared to that of kidney transplant (KT) recipients who have the lowest rate of infections among the different populations of solid organ transplant recipients. Patients and Methods Matched cohort study among UEA and KT recipients from the prospectively maintained “International Registry on Hand and Composite Tissue Transplantation” (IRHCTT) and the French “Données Informatisées et VAlidées en Transplantation” (DIVAT) database. All UEA recipients reported to the IRHCTT between 1998 and 2016 were matched with KT recipients (1:5), according to age (±5 years), sex, CMV serostatus of donor and recipient and (depleting or not depleting) induction. Incidence and characteristics of all infectious events reported to the databases at three posttransplant periods (0-6 months, 7-12 months, >12 months) were analyzed. Results and Discussion Sixty-one UEA recipients were matched with 305 KT recipients. Mean (±SD) follow-up of UEA and KT recipients was 2583±1876 and 2230±1792 days, respectively (p=0.16). Immunosuppression regimen at 3 months posttransplant was similar. The number of acute rejection episodes during follow-up was higher in UEA recipients than in KT recipients (1.3±1.6 vs 0.4±0.7, p<0.01). During follow-up, 30 (50.8%) UEA recipients presented a total of 61 infectious events while 129 (42.3%) KT recipients presented 243 infectious events. Incidence rate of infectious events was higher in UEA recipients than in KT recipients during the first 6 months posttransplant (3.27 vs 1.95 events/1000 transplant-days, p=0.01). Thereafter, incidence rates of infections did not significantly differ between UEA and KT recipients: 0.61 vs 0.45 events/1000 transplant-days (7th-12th month posttransplant, p=0.5) and 0.15 vs 0.21 events/1000 transplant-days (>12th month posttransplant, p=0.11), respectively. Distribution of sites of infections was significantly different: while mucocutaneous infections predominated among UEA recipients at each of the three posttransplant periods (representing 28.6%, 50% and 30% of infectious events, respectively), urinary tract infections (28.6%, 23.8% and 33.9%) and pneumonia (17.3%, 42.9% and 28.2%) predominated among KT recipients. Conclusion Incidence rate of infectious events is higher in UEA recipients than in KT recipients during the first 6 months posttransplant. After the first 6 months posttransplant, incidence of infections is low, at worst equivalent to the incidence observed in young KT recipients. Distribution of infectious syndromes suggests less severe infections in UEA than in KT recipients.

OF PHOTOPHERESIS IN KIDNEY TRANSPLANTATION

Aim– to perform a comparative study of the long-term results of the combined use of extracorporeal photochemotherapy (photopheresis) and drug immunosuppression and standard immunosuppressive therapy in patients after kidney transplantation.Materials and methods. An open cohort randomized study was conducted, including 60 patients with chronic kidney disease stage 5D. All patients underwent single-group cadaveric kidney transplantation. Patients were randomly divided into two groups. All transplants were paired, the fi rst kidney transplant was received by the patient of the main group, the second – by comparison group. 30 patients of the main group received standard protocol of immunosuppression and 10–15 sessions of photopheresis during the fi rst six months after transplantation. All patients of the comparison group received standard immunosuppressive therapy only. End points: primary – graft loss, surrogate – the number of acute rejection episodes and infectious complications, the dynamics of creatinine blood concentration, the glomerular fi ltration rate and daily proteinuria, the dynamics of tacrolimus C0 blood concentration. To study the mechanism of photopheresis action in the late postoperative period, we evaluated the immunological parameters: subpopulation of naive T-cells (CD3+CD4+CD45RO–CD28+), the level of CD28 molecule expression (MFI) on these cells and also – subpopulation of T-regulatory cells (CD3+CD4+CD25 (Hi)CD127–).Results.The use of photopheresis leads to the graft function improvement in the late postoperative period: the creatinine concentration (p = 0.017) in the blood and daily proteinuria (p = 0.011) were lower in patients of the main group, the glomerular fi ltration rate was higher (p = 0.027). The incidence rate ratio (IRR) of rejection in the main group was signifi cantly lower than in the comparison group: 0.2509 (95% CI 0.05386, 0.9167), p = 0.0358. The risk of graft loss was also lower in the main group: IRR 0.2782 (95% CI 0.07562, 0.8657), p = 0.026, as well as the risk of infectious complications: IRR 0.3888 (95% CI 0.2754; 0, 5445), p &lt; 0.0001. Survival rate of transplants was higher in the main group (Log Rank p = 0.009; Breslow p = 0.005). The use of photopheresis made it possible to reduce the concentration of tacrolimus in the late postoperative period (p = 0.0017) without increasing the risk of graft rejection. The photopheresis tolerogenic effect in the late postoperative period may be due to an increase in the population of T-regulatory cells with the CD3+CD4+CD25(Hi)+CD127– phenotype compared to the patients which received only standard immunosuppressive therapy (p = 0.024).Conclusion.The preventive use of photopheresis contributes to improvement of the kidney transplantation long-term outcomes. Further studies are needed to study the mechanisms of photopheresis action and markers of partial immunological tolerance to the allograft.

Nationwide conversion to generic tacrolimus in pediatric kidney transplant recipients.

Bioequivalence between Tacrolimus Prograf® and generic tacrolimus formulations has been demonstrated in adult populations, however clinical experience and safety data regarding generic tacrolimus in pediatric transplant recipients is limited. This study aimed to evaluate conversion from Tacrolimus Prograf® to Sandoz® in pediatric renal transplant recipients nationwide. The primary outcome was a change in mean trough tacrolimus concentration. Additionally, changes in tacrolimus intra-patient coefficient of variation (CoV), allograft function, requirement for dose adjustments, and episodes of biopsy-proven rejection were evaluated. Retrospective cohort study in 37 pediatric renal transplant recipients who switched to Tacrolimus Sandoz®. Each patient had three pre-conversion tacrolimus trough and creatinine concentrations within the 4months prior and three post-conversion concentrations on day 3, 10, and the next subsequent level. Mean pre- and post-conversion tacrolimus trough concentrations and glomerular filtration rate (eGFR) were calculated. Tacrolimus concentration, CoV, and creatinine differences were compared by paired ttest. Thirty-seven patients (41% females, age 3-18 years) were included. Average intra-patient difference in trough tacrolimus concentration was 0.05μg/l (95% CI -0.37 to 0.47). Average intra-patient difference in eGFR was -1.20ml/min/1.732 (95%CI -3.53 to 1.13). Three patients had acute rejection during 12 months post-conversion compared to none during 12 months pre-conversion. Pediatric renal transplant recipients can be converted from Tacrolimus Prograf® to Sandoz® with negligible change in trough concentration, dose adjustments, or immediate allograft function. Of concern was the number of acute rejection episodes, however non-adherence contributed to at least one episode and this difference was determined clinically and statistically not significant.

Regional differences in the management and outcome of kidney transplantation in patients with human immunodeficiency virus infection: A 3-year retrospective cohort study.

In the developed world, kidney transplantation (KT) in patients with human immunodeficiency virus (HIV) infection is well established. Developing countries concentrate 90% of the people living with HIV, but their experience is underreported. Regional differences may affect outcomes. We compared the 3-year outcomes of patients with HIV infection receiving a KT in two different countries, in terms of incomes and development. This was an observational, retrospective, double-center study, including all HIV-infected patients >18years old undergoing KT. Between 2005 and 2015, 54 KTs were performed (39 in a Brazilian center, and 15 in a Spanish center). Brazilians had less hepatitis C virus co-infection (5% vs 27%, P=.024). Median cold ischemia time was higher in Brazil (25 vs 18hours, P=.001). Biopsy-proven acute rejection (AR) was higher in Brazil (33% vs 13%, P=.187), as were the number of AR episodes (22 vs 4, P=.063). Patient survival at 3years was 91.3% in Brazil and 100% in Spain; P=.663. All three cases of death in Brazil were a result of bacterial infections within the first year post transplant. At 3years, survival free from immunosuppressive changes was lower in Brazil (56% vs 90.9%, P=.036). Raltegravir-based treatment to avoid interaction with calcineurin inhibitor was more prevalent in Spain (80% vs 3%; P<.001). HIV infection remained under control in all patients, with undetectable viral load and no opportunistic infections. Important regional differences exist in the demographics and management of immunosuppression and antiretroviral therapy. These details may influence AR and infectious complications. Non-AIDS infections leading to early mortality in Brazil deserve special attention.

MP30-13 MTH SCORE – A NOVEL SCORING SYSTEM TO RISK STRATIFY RENAL TRANSPLANT CASES AND TO IMPROVE OUTCOMES POST RENAL TRANSPLANT

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II1 Apr 2017MP30-13 MTH SCORE – A NOVEL SCORING SYSTEM TO RISK STRATIFY RENAL TRANSPLANT CASES AND TO IMPROVE OUTCOMES POST RENAL TRANSPLANT aditya yelikar and sachin joseph aditya yelikaraditya yelikar More articles by this author and sachin josephsachin joseph More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.946AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES ESRD is a highly prevalent cause of morbidity and mortality. Kidney transplantation is the optimal treatment of ESRD in terms of morbidity, mortality and quality of life. Maximum incidence of graft dysfunction in the first year post transplant. We wanted to study the pre and post transplant factors that can affect post transplant outcome and graft survival. We wanted to make a scoring system to predict outcomes post transplant. METHODS 450 cases of live donor renal transplant were studied in a period of 2 years. all recipients were followed for 1 year and their mean serum creatinine was considered to compare the outcomes post transplant. We studied the pre-transplant & post-transplant factors like donor age , donor sex , ratio of donor kidney weight to recipient body weight , recipient age , donor to recipient sex , cold ischemia time , time for diuresis , number of blood transfusions to recipient , amount of steroids taken by recipient in first 3 months after transplant , number of acute rejection episodes , number of renal arteries , hepatitis C virus infection of recipient. using these factors we made 3 score charts (pre transplant,post transplant & combined MTH score) by giving points in ascending order starting from 1 to each subgroup of the factors affecting transplant outcome. Maximum points were given to the category in the subgroup which has the best impact on the transplant outcome. We classified patients into low (score >30), intermediate risk (score 21-30) and high risk (score 11-20). Independent t test or Mann Witney U test (∗) was used as test of significance to identify the mean difference between two groups. ANOVA (Analysis of Variance) or Kruskal Wallis test (∗∗) was the test of significance to identify the mean difference between more than two groups. p value <0.05 was considered as statistically significant. RESULTS Overall 89.76% recipients had a serum creatinine of less than 2 at the end of one year 54.54 % recipients in MTH high risk group had serum creatinine < 2 at the end of 1 year. 96.72 % recipients in MTH low risk group had serum creatinine < 2 at the end of 1 year 27.27% recipients in MTH high risk group were restarted on HD in the first year post renal transplant CONCLUSIONS 1. MTH score can help risk stratify renal transplant cases 2. The MTH score can help predict the outcomes in renal transplant 3. MTH score can be a guide for future scoring systems in transplant 4. Modifying the risk factors can help high risk cases to fall into low risk category and may improve post transplant graft survival rates in the first year. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e394 Advertisement Copyright & Permissions© 2017MetricsAuthor Information aditya yelikar More articles by this author sachin joseph More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Role of Everolimus on Cardiac Functions in Kidney Transplant Recipients

BackgroundKidney transplantation is known to increase the survival of dialysis patients by ameloriating cardiac status, including both systolic and diastolic functions. We aimed to evaluate the role of immunosuppressive drug regimens on cardiac functions of kidney transplant recipients (KTRs). MethodsWe prospectively evaluated 120 KTRs immediately before and 1 year after the kidney transplantation, using tissue Doppler echocardiography. A triple immunosuppressive therapy including tacrolimus, mycophenoloic acid (MPA), and prednisolone was started for all patients. After 3 to 6 months, the tacrolimus dose was lowered to achieve target serum levels of 5 to 8 ng/mL in both groups. MPA was switched to everolimus, with target levels of 4 to 6 ng/mL, in group 1 (n = 58), whereas group 2 (n = 62) continued with MPA. ResultsNo differences in age, sex, or dialysis duration existed between the groups. The prevalence of diabetic or hypertensive nephropathy as the etiology of chronic kidney disease was similar. Blood pressure was strictly controlled. The number of acute rejection episodes was not different in both groups, and no graft loss was observed in either group. Improvement in cardiac parameters including ejection fraction, left ventricular diastolic diameter, posterior wall thickness, and left ventricular hypertrophy was significantly better before and 1 year after transplantation. Interestingly, when compared with group 2, ameloriation of all of the parameters mentioned above was even better in group 1 patients (P = .02, P = .03, P = .04, and P = .04, respectively). Multivariate analysis of the significant variables determined by univariate analysis identified albumin (relative risk [RR] = 1.05, P = .02) and everolimus (RR = 1.07, P = .01) as two independent factors of improving cardiovascular function. ConclusionsBetter ameloriation of cardiovascular functions with everolimus may favor the choice of this drug in KTRs.

Alemtuzumab Induction and Delayed Acute Rejection in Steroid-Free Simultaneous Pancreas-Kidney Transplant Recipients.

The optimal immunosuppressive regimen in simultaneous pancreas-kidney transplant (SPKT) recipients that prevents acute rejection episodes (AREs) and allows optimal outcome remains elusive. This cohort study assessed incidence and time to AREs in 73 consecutive SPKT recipients receiving alemtuzumab induction and steroid-free maintenance with tacrolimus and mycophenolate mofetil. A cohort with single high-dose antithymocyte globulin (ATG; n = 85) and triple therapy served as controls. In addition, we provided mechanistic insights in AREs after alemtuzumab depletion, including composition and alloreactivity of lymphocytes (flow cytometry and mixed lymphocyte reaction) plasma alemtuzumab levels (enzyme-linked immunosorbent assay), and maintenance drug exposure. Overall number of AREs at 3 years was significantly lower with alemtuzumab versus ATG induction (26.0% vs 43.5%; adjusted hazard ratio, 0.38; P = 0.029). Most AREs (94.6%) with ATG occurred within the first month, whereas 84.2% of AREs with alemtuzumab occurred beyond 3 months. Patients with and without an ARE in the steroid-free alemtuzumab group showed no differences in composition of lymphocytes, or in alemtuzumab levels. Of note, more than two thirds of these AREs were preceded by empiric tacrolimus and/or mycophenolate mofetil dose adjustments due to viral infections, leukopenia, or gastrointestinal symptoms. Alemtuzumab induction resulted in a significant lower incidence of AREs. Empiric dose adjustments beyond 3 months in the absence of steroids carry a significant risk for subsequent rejection in SPKT recipients.

Kidney Transplantation From Brain-Dead Donors: Initial Experience in China.

Experience with kidney transplantation from brain-dead donors remains limited in China. Our objective was to evaluate the outcomes of kidney transplantation from brain-dead donors (group 1), compared with those from living ones of the same age (group 2). Clinical data of kidney transplantation from brain-dead donors and living donors in the same age range (18-45 years) performed between May 2007 and December 2011 were analyzed retrospectively. Recipients were analyzed for posttransplantation serum creatinine, creatinine clearance (calculated by the Cockcroft-Gault formula), the number of acute rejection episodes and delayed graft function, and patient/graft survival. Mean donor age was comparable between the 2 groups (31.9 ± 6.5 vs 32.8 ± 7.0 years; P= .268). The terminal serum creatinine level of donors was 125.5 ± 63.5 μmol/L in group 1 (n= 30) and 65.1 ± 13.7 μmol/L in group 2 (n= 110; P= .000). Recipient creatinine clearance was comparable between the 2 groups 1 month posttransplantation and thereafter. Acute rejection episodes were seen in 7 cases in recipients of group 1 (15.9%) and in 15 cases in recipients of group 2 (13.6%; P= .716). The incidence of delayed graft function was higher in recipients of group 1 (18.2%) than that of group 2 (3.6%; P= .002). The 1-, 3-, and 5-year patient/graft survival rate was comparable between the 2 groups. Our study demonstrated kidney transplantation from brain-dead donors achieved acceptable graft function and patient/graft survival in the 5-year follow-up, encouraging the use of this approach.

Functional outcomes and quality of life after normothermic ex vivo lung perfusion lung transplantation

Ex vivo lung perfusion (EVLP) is an effective method to assess and improve the function of otherwise unacceptable lungs, alleviating the shortage of donor lungs. The early results with EVLP have been encouraging, but longer-term results, including functional and patient-reported outcomes, are not well characterized. This retrospective single-center study included all lung transplants performed between September 2008 and December 2012. We investigated whether survival or rate of chronic lung allograft dysfunction (CLAD) differed in recipients of EVLP-treated lungs compared with contemporaneous recipients of conventional donor lungs. We also studied functional (highest forced expiratory volume in 1 second predicted, change in 6-minute walk distance, number of acute rejection episodes) and quality of life outcomes. Of 403 lung transplants that were performed, 63 patients (15.6%) received EVLP-treated allografts. Allograft survival for EVLP and conventional donor lung recipients was 79% vs 85%, 71% vs 73%, and 58% vs 57% at 1, 3, and 5 years after transplant, respectively (log-rank p = not significant). Freedom from CLAD was also similar (log-rank p = 0.53). There were no significant differences in functional outcomes such as highest forced expiratory volume in 1 second predicted (76.5% ± 23.8% vs 75.8% ± 22.8%, p = 0.85), change in 6-minute walk distance (194 ± 108 meters vs 183 ± 126 meters, p = 0.57), or the number of acute rejection episodes (1.5 ± 1.4 vs 1.3 ± 1.3, p = 0.36). The EVLP and conventional donor groups both reported a significantly improved quality of life after transplantation, but there was no intergroup difference. EVLP is a safe and effective method of assessing and using high-risk donor lungs before transplantation and leads to acceptable long-term survival, graft function, and improvements of quality of life that are comparable with conventionally selected donor lungs.

Impact of Pretransplant Body Mass Index on Early Kidney Graft Function

BackgroundAn increase in the number of obese patients on transplantation waiting lists can be observed. There are conflicting results regarding the influence of body mass index (BMI) on graft function. MethodsWe performed a single-center, retrospective study of 859 adult patients who received a renal graft from deceased donors. BMI (kg/m2) was calculated from patients' height and weight at the time of transplantation. Kidney recipients were subgrouped into 4 groups, according to their BMI: Groups A (<18.5; n = 57), B (18.6–24.9; n = 565), C (25–29.9; n = 198) and D (>30; n = 39). Primary or delayed graft function (DGF), acute rejection (AR) episodes, and number of reoperations, graft function expressed by glomerular filtration rate (GFR) and serum creatinine concentration and number of graft loss as well as the recipient's death were analyzed. The follow-up period was 1 year. ResultsObese patients' grafts do not develop any function more frequently in comparison with their nonobese counterparts (P < .0001; odds ratio [OR], 32.364; 95% CI, 2.174–941.422). Other aspects of the procedure were analyzed to confirm that thesis: Cold ischemia time and number of HLA mismatches affect the frequency of AR (OR, 1.0182 [P = .0029] and OR, 1.1496 [P = .0147], respectively); moreover, donor median creatinine serum concentration (P = .00004) and cold ischemia time (P = .00019) are related to delayed graft function. BMI did not influence the incidence of DGF (P = .08, OR; 1.167; 95% CI, 0.562–2.409), the number of AR episodes (P > .1; OR, 1.745; 95% CI, 0.846–3.575), number of reoperations, GFR (P = .22–.92), or creatinine concentration (P = .09). Number of graft losses (P = .12; OR, 1.8; 95% CI, 0.770–4.184) or patient deaths (P = .216; OR, 3.69; 95% CI, 0.153–36.444) were not influenced. ConclusionGreater recipient BMI at the time of transplantation has a significant influence on the incidence of primary graft failure.

Association of soluble HLA-G with acute rejection episodes and early development of bronchiolitis obliterans in lung transplantation.

Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, long-term survival remains limited because of bronchiolitis obliterans syndrome (BOS). Soluble HLA-G, a mediator of adaptive immunity that modulates regulatory T cells and certain classes of effector T cells, may be a useful marker of survival free of BOS. We conducted a retrospective, single-center, pilot review of 38 lung transplant recipients who underwent collection of serum and bronchoalveolar lavage fluid 3, 6 and 12 months after transplantation, and compared soluble HLA-G concentrations in each to the presence of type A rejection and lymphocytic bronchiolitis in the first 12 months and to the presence of BOS at 24 months after transplantation. Lung soluble HLA-G concentrations were directly related to the presence of type A rejection but not to lymphocytic bronchiolitis. Our data demonstrate that soluble HLA-G concentrations in bronchoalveolar lavage but not in serum correlates with the number of acute rejection episodes in the first 12 months after lung transplantation, and thus may be a reactive marker of rejection.

Prognostic Value of Post-Transplantation Proteinuria for Cardiovascular Outcomes in Kidney Transplant Recipients.

Background: Proteinuria has been shown to be associated with mortality, progression to kidney failure, and cardiovascular disease events in general population. Herein, we have analyzed the effect of proteinuria on cardiovascular outcomes, graft loss, and mortality in kidney transplant recipients (KTRs). Methods: We performed a retrospective multi-center study to evaluate the effect of post-transplantation proteinuria on cardiovascular outcomes, graft loss, and patients' survival. This study enrolled a total of 2052 KTRs in Seoul National University Hospital and Asan Medical Center, and patients were classified into three groups according to the amount of proteinuria (<150mg/day [group 1] vs. 150-1500mg/day [group 2] vs. >1500mg/day [group 3]). The primary endpoint was major adverse cardiac events (MACE), defined as composite cardiac death, nonfatal myocardial infarction, or coronary revascularization. Results: The mean age of the recipients was 43.6 ± 11.4 years, and 58.6% were male. During a median 55.3-month follow-up, there were 38 (1.9%) cases of MACE, 71 (3.5%) graft loss, and 44 (2.1%) deaths. In a Cox model adjusted with multiple covariates, proteinuria was significantly associated with MACE (group 1 [reference] vs. group 2 [HR 3.29, CI 1.02-10.60, P = 0.046] vs. group 3 [HR 5.81, CI 1.28-26.31, P = 0.022]). KTRs with higher proteinuria showed significantly higher graft loss rate than those without proteinuria (group 1 [reference] vs. group 3 [HR 3.97, CI 1.65-9.56, P = 0.002]). However, there was no significant association between proteinuria and all-cause mortality. KTRs with proteinuria showed a greater number of acute rejection episodes (10.5% [group 1] vs. 20.5% [group 2] vs. 37.1% [group 3], P < 0.001) Conclusion: Post-transplantation proteinuria is a strong prognostic factor for cardiovascular outcomes among KTRs. Therefore, evaluation and management of proteinuria should be considered to improve graft and patients outcomes.

Influence of allograft weight to recipient bodyweight ratio on outcome of cadaveric renal transplantation.

One of the factors that may affect survival and function of kidney graft is its functional mass. In a prospective study, we investigated the impact of the ratio between donor kidney weight in grams and recipient bodyweight in kilograms (DKW/RBW) on creatinine clearance, inulin clearance, and proteinuria: 154 kidneys from deceased donors were weighed and the mean kidney weight was 227 ± 59 g, the bodyweight of the recipients was 64 ± 19 kg. This study showed significant lower values of modification of diet in renal disease (MDRD) in patients with DKW/RBW ratio 2.5 g/kg and between 2.5 and 4.5 g/kg compared with those with DKW/RBW ratio >4.5 g/kg as well as in patients with DKW/RBW ratio <3 g/kg and between 3 and 4 g/kg compared with those with DKW/RBW ratio >4 g/kg; moreover a random coefficient model showed a different time evolution in creatinine clearance values in patients with DKW/RBW ≤ 3 g/kg when compared with patients with DKW/RBW ratio >4 g/kg. There were significant lower values of inulin clearance in patients with DKW/RBW ratio between 2.5 and 4.5 g/kg compared with those with DKW/RBW ratio >4.5 g/kg at 12 post-transplant months and a significantly greater occurrence and earlier appearance of proteinuria in the recipients with DKW/RBW ratio <2.5 g/kg. DKW/RBW ratio did not influence DGF incidence and graft survival. Donor and recipient gender, number of acute rejection episodes and donor age also significantly influenced MDRD values. Measurements of graft weight as well as donor kidney and recipient body matching should be recommended as influencing renal function.

Glucocorticoid resistance in dialysis patients reduces long-term graft survival after kidney transplantation

Glucocorticoid (GC) resistance has been observed in chronic kidney disease (CKD) patients on dialysis. It can be evaluated by binding assays based on the dissociation constant (Kd), which is inversely proportional to ligand affinity. CKD patients with GC resistance had increased number of acute rejection episodes. We followed up 26 patients that underwent kidney transplantation to observe whether GC resistance could affect the response to acute rejection episode pulse therapy and the long-term allograft outcome. Using Kaplan–Meier survival curve, GC resistant patients showed lower acute rejection-free survival (p=0.03) and lower kidney allograft survival (p=0.008). No difference was found regarding number of deaths. Multivariate logistic regression showed that high Kd value was an independent predictor of lower kidney allograft survival (p=0.001). There was a negative Spearman correlation between Kd and kidney allograft survival (r=−0.88, p=0.03). In conclusion, our findings indicate the usefulness of binding assay performed previously to kidney transplantation to define GC resistance. In addition, the dissociation constant (Kd) is a reliable and independent predictive marker of higher frequency of acute rejection episodes, lower rejection-free graft survival, poor response of acute rejection episodes to methylprednisolone pulse therapy, and lower kidney allograft survival in a long-term follow-up.

Survival of living donor renal transplant recipients in Sri Lanka: a single-center study.

Chronic kidney disease is one of the main public health concerns in Sri Lanka. In comparison with dialysis, successful kidney transplantation improves both patient survival and quality of life, relieves the burden of dialysis in patients suffering from end-stage renal disease and decreases the cost of healthcare to the society and government. The objective of this retrospective cohort study was to evaluate graft and patient survival rates in patients who were transplanted from living donors at the Nephrology Unit of the National Hospital of Sri Lanka from January 2005 to January 2011. Data were collected using an interviewer-administered questionnaire and through a review of past medical records. The Kaplan-Meier method was used to determine the survival rate, the log rank test was used to compare survival curves and the Cox proportional hazard model was used for multivariate analysis. Mean follow-up was 26.44±16.6 months. The five-year death-censored graft survival of kidney transplant recipients from living donors in our center was 93.5% and the five-year patient survival was 82.2%, which is comparable with other transplant programs around the world. The number of acute rejection episodes was an independent risk factor for graft survival. Delayed graft function, younger recipient age and unknown cause of end-stage renal disease were found to be risk factors for graft failure but after adjusting for confounding factors, and the difference was not apparent.

Deferred Pre-Emptive Switch from Calcineurin Inhibitor to Sirolimus Leads to Improvement in GFR and Expansion of T Regulatory Cell Population: A Randomized, Controlled Trial

BackgroundMeasures to prevent chronic calcineurin inhibitor (CNI) toxicity have included limiting exposure by switching to sirolimus (SIR). SIR may favorably influence T regulator cell (Treg) population. This randomized controlled trial compares the effect of switching from CNI to SIR on glomerular filtration rate (GFR) and Treg frequency.MethodsIn this prospective open label randomized trial, primary living donor kidney transplant recipients on CNI-based immunosuppression were randomized to continue CNI or switched to sirolimus 2 months after surgery; 29 were randomized to receive CNI and 31 to SIR. All patients received mycophenolate mofetil and steroids. The main outcome parameter was estimated GFR (eGFR) at 180 days. Treg population was estimated by flowcytometry.ResultsBaseline characteristics in the two groups were similar. Forty-eight patients completed the trial. At six months, patients in the SIR group had significantly higher eGFR as compared to those in the CNI group (88.94±11.78 vs 80.59±16.51 mL/min, p = 0.038). Patients on SIR had a 12 mL/min gain of eGFR of at the end of six months. Patients in the SIR group showed significant increase in Treg population at 30 days, which persisted till day 180. There was no difference in the adverse events in terms of number of acute rejection episodes, death, infections, proteinuria, lipid profile, blood pressure control and hematological parameters between the two groups. Four patients taking SIR developed enthesitis. No patient left the study or switched treatment because of adverse event.ConclusionsA deferred pre-emptive switch over from CNI to SIR safely improves renal function and Treg population at 6 months in living donor kidney transplant recipients.Registered in Clinical Trials Registry of India (CTRI/2011/091/000034)