Search

Background: To describe and establish the efficacy and safety of Mycophenolate Mofetil (Micoflavin) in patients with de novo renal transplantation during one-year post-transplant follow-up. As secondary objectives, the behavior of mycophenolic acid (MPA) C0 levels in this population, the relationship between MPA levels and renal function of the grafts, the incidence of acute rejection, and the incidence of adverse effects were evaluated., Methods: A prospective cohort study was conducted on patients who received a first kidney transplant from a deceased donor between March 1, 2021, and February 28, 2022, at the Alma Mater of Antioquia Hospital of the Antioquia's University, in Medellín, Colombia. MPA C0 levels were taken from the patients on days 15, 30, 90, 180, and 360 after the kidney transplantation., Results: Patients presented MPA therapeutic levels in the study. The average of the MPA levels in the population was 2.5 µg/mL, with an IQR of 2.13 to 3.32. There were 5 acute rejections (27%), but none of the patients with acute rejection presented subtherapeutic levels of mycophenolate. No significant relationship was observed between mycophenolic acid levels and rejection (P = .255). The patients who completed the study had no gastrointestinal intolerance to mycophenolate, cytomegalovirus infections, or significant hematological complications., Conclusions: MMF (Micoflavin) maintained mycophenolic acid levels C0 within the therapeutic range, was well tolerated and without the presence of significant adverse events, and maintained stable renal function throughout the follow-up period in the population studied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: With the aging of the population, more older patients are being considered for kidney transplantation; therefore, it is crucial to evaluate the risks and benefits of transplantation in this population. This study aimed to assess long-term outcomes of kidney transplantation in a cohort of patients who underwent kidney transplantation at age >70 years, compared with patients aged 60 to 69 years at transplantation., Methods: Included in the study were 261 consecutive kidney transplant recipients: 52 were aged >70 years, and 209 were aged 60 to 69 years at transplantation. Data were collected retrospectively and analyzed using multivariate logistic regression to identify potential outcome risk factors., Results: The number of transplants in both groups increased during the study period. Mortality after transplantation was strongly correlated to age (hazard ratio [HR] = 1.11; 95% CI, 1.05-1.18; P < .001), deceased donor (HR = 2.0; 95% CI, 1.1-3.8; P = .034), and pretransplant diabetes (HR = 2.9; 95% CI, 1.7-4.9; P = .001). Recipients aged >70 years had an increased risk of death censored graft failure (HR = 2.98; 95% CI, 1.56-5.74; P = .001). In living donor transplants, 3-year survival was 80% in recipients age >70 years, compared with 98% in the 60- to 69-year group. Five-year survival was 71% and 92%, respectively. In deceased donor transplants, 3-year survival was 63% and 78%, and 5-year survival was 58% and 72%, respectively. The risk of malignancy (excluding nonmelanotic skin cancer) was nearly triple in the age >70 years group (HR = 2.96; 95% CI, 1.3-6.8; P = .01)., Conclusions: Patient and graft survival in kidney recipients in the eighth decade is worse compared with recipients in the seventh decade of life. However, it is improved with living kidney donation., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The majority of kidney recipients are a subset of chronic kidney disease. Our previous study demonstrated that the combination of Lactobacillus plantarum and Lactobacillus paracasei (Lm) had the highest clearance ability of uremic toxins and improved kidney function in a mouse model. This study aimed to evaluate Lm in improving graft function, effects on immunosuppressants, and safety in transplant recipients., Methods: We retrospectively reviewed 24 patients. Twelve of them take Lm regularly; we compared the creatinine measurements and estimated glomerular filtration rate 3 months before and after Lm using a 2-tailed Wilcoxon matched-pairs signed-rank test while also evaluating the drug level of immunosuppressants and infection events. Other 12 patients who do not have Lm for evaluation of laboratory calibration and compared the proportion of improving creatinine using Fisher's exact test., Results: The creatinine decreased by 0.06 mg/dL (P = .02), and the estimated glomerular filtration rate increased by 3.1 mL/min/1.73 m 2 (P = .03) after Lm supplementation. This pilot study revealed the association of higher incidence (odds ratio 13.3, 95% CI 1.64-77.2, P = .01) of decreasing creatinine in transplant recipients using Lm. Furthermore, results showed a trend of higher trough levels of tacrolimus and sirolimus, which might provide a potential strategy for reducing the dosages of immunosuppressants., Conclusion: Our findings revealed an association between a higher incidence of decreasing creatinine in kidney transplant recipients using Lm, which may also provide a potential strategy for reducing the acquired dosages of immunosuppressants., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: This retrospective analysis of the US Scientific Registry of Transplant Recipients was undertaken to obtain real-world evidence concerning the efficacy and safety of tacrolimus-based immunosuppression in pediatric lung transplant recipients to support a supplemental New Drug Application., Methods: Overall, 725 pediatric recipients of a primary deceased-donor lung transplant between January 1, 1999, and December 31, 2017, were followed for up to 3 years post-transplant based on an immunosuppressive regimen at hospital discharge: immediate-release tacrolimus (TAC)+mycophenolate mofetil (MMF), TAC+azathioprine (AZA), cyclosporine (CsA)+MMF, or CsA+AZA. The primary outcome was the composite endpoint of graft failure or death (all-cause) at 1 year post-transplant, calculated by Kaplan-Meier analysis., Results: The use of TAC+MMF increased over time. During 2010 to 2017, 91.7% of pediatric lung transplant recipients were receiving TAC+MMF at the time of discharge. The proportion of recipients continuing their discharge regimen at 1 year post-transplant was 83.7% with TAC+MMF and 40.4% to 59.7% with the other regimens. Cumulative incidence of the composite endpoint of graft failure or death at 1 year post-transplant was 7.7% with TAC+MMF, 13.9% with TAC+AZA, 8.9% with CsA+MMF, and 9.1% with CsA+AZA. There was no significant difference in the risk of graft failure or death at 1 year post-transplant between groups from 1999 to 2005 (the only era when adequate numbers on each regimen allowed statistical comparison). No increase in hospitalization for infection or malignancy was seen with TAC+MMF., Conclusion: The real-world evidence from the US database of transplant recipients supported the Food and Drug Administration's approval of tacrolimus-based maintenance immunosuppression in pediatric lung transplant recipients., Competing Interests: Declaration of Competing Interest All authors report non-financial support from Astellas during the conduct of the study. Jay Erdman, David Nimke, Richard Croy, and Xuegong Wang are employees of Astellas Pharma, Inc. Josephine Wolfram is an employee of Astellas Pharma Europe BV. Tim Weaver and David Schladt are employees of Chronic Disease Research Group, an organization that generated data on behalf of Astellas. William E. Fitzsimmons is a former employee of Astellas Pharma, Inc. and is currently a pharma consultant working on behalf of Astellas, a co-founder of Azoth Immune Medicines, Inc, an advisory board member of CTI Clinical Trial and Consulting Services, a senior advisor to the Transplant Therapeutics Consortium, C-Path, and founder of Tutela Pharmaceuticals, Inc., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The literature has shown a significant association between body mass index (BMI) and patient and graft outcomes after renal transplantation. The purpose of this study was to reveal the effect of obesity on graft function in a Taiwanese kidney transplant cohort., Methods: Two hundred consecutive patients who received kidney transplantation were enrolled in our study. Eight pediatric cases were excluded due to differing definitions of BMI among children. According to the national obesity criteria, these patients were divided into underweight, normal, overweight, and obese groups. Their estimated glomerular filtration rate (eGFR) was compared accordingly using t tests. Cumulative graft and patient survivals were calculated using Kaplan-Meier analysis. A P value of ≤ .05 was considered significant., Results: The mean age of our cohort (105 men and 87 women) was 45.3 years. There was no significant difference comparing biopsy-proven acute rejection, acute tubular necrosis, and delayed graft function between the obese and nonobese groups (P values: .293, .787, and .304, respectively). Short-term eGFR was inferior in the overweight group, but this effect was insignificant beyond 1 month. The 1-month and 3-month eGFR were found to be correlated with BMI groups (P = .012 and P = .008, respectively) but not significant after 6 months post-kidney transplantation., Conclusions: Our study found that short-term renal function was affected by obesity and being overweight, possibly due to the higher prevalence of diabetes and dyslipidemia in obese patients and the increased surgical difficulty., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Subclinical rejection (SCR) is associated with chronic allograft nephropathy. Therefore, early detection and treatment of SCR through a protocol biopsy (PB) can reduce the incidence of pathologic changes. This study evaluates the impact of early detection and treatment of SCR using a routine PB 2 weeks after kidney transplantation (KT) by examining histologic outcomes 1 year later. We reviewed 624 KT recipients at the Samsung Medical Center between August 2012 and December 2018. Protocol biopsy was planned 2 weeks and 1 year after transplantation. We compared the histologic changes between the 2 biopsies. After a propensity score matching analysis, we divided the patients into 2 groups: the proven normal group (n = 256) and the rejection group (n = 96) at the PB taken 2 weeks post-transplant. The rejection group showed no significant difference from the normal group in the flow of graft function or the Kaplan-Meier curve for graft survival. In the histologic outcomes, the pathologic differences between the groups significantly improved between the 2 time points. Treating SCR through a PB 2 weeks after KT can contribute to the maintenance of graft function and improve histologic changes 1 year after KT., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study is to evaluate the impact of intraoperative allograft vascular flow on early kidney graft function., Methods: A total of 159 patients underwent kidney transplantation from January 2017 to March 2022 at Linkou Chang Gung Memorial Hospital. Graft arterial and venous blood flow was measured separately with a transient time flowmeter (Transonic HT353; Transonic Systems, Inc, Ithaca, NY, United States) after ureteroneocystostomy. The early outcomes, including the postoperative creatinine level, were analyzed accordingly., Results: There were 83 males and 76 females, with a mean age of 44.5 years. The mean graft arterial flow measured was 480.6 mL/min, and the mean venous flow was 506.2 mL/min. Delayed graft function (DGF) incidence was 36.5%, 32.5%, and 40.8% in total, living, and deceased donor groups, respectively. Living donor and deceased donor kidney transplantation were analyzed separately. In the DGF subgroup, there were lower graft venous flows, higher body mass index (BMI), and more male patients in the living kidney transplant group. Similarly, the deceased donor kidney transplantation group with delayed graft function tended to have higher body height, higher body weight, higher BMI, and more diabetes mellitus. The multivariate analysis showed that lower graft venous blood flow (odds ratio [OR] = 0.995, P = .008) and higher BMI (OR = 1.144, P = .042) were significantly correlated with delayed graft function in living donor kidney transplantations. In the deceased donor group, a multivariate analysis of risk factors showed that BMI had a significant correlation with delayed graft function (OR = 1.41, P = .039)., Conclusions: Graft venous blood flow was significantly associated with delayed graft function in living donor kidney transplantation, and high BMI was correlated with DGF in all patients receiving kidney transplantation., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Many studies have reported that protocol biopsy (PB) may help preserve kidney function in kidney transplant recipients. Early detection and treatment of subclinical rejection may reduce the incidence of chronic antibody-mediated rejection and graft failure. However, no consensus has been reached regarding PB effectiveness, timing, and policy. This study aimed to evaluate the protective role of routine PB performed 2 weeks and 1 year after kidney transplantation. We reviewed 854 kidney transplant recipients at the Samsung Medical Center between July 2007 and August 2017, with PBs planned at 2 weeks and 1 year after transplantation. We compared the trends in graft function, chronic kidney disease (CKD) progression, new-onset CKD, infection, and patient and graft survival between the 504 patients who underwent PB and 350 who did not undergo PB. The PB group was again divided into 2 groups: the single PB group (n = 207) and the double PB group (n = 297). The PB group was significantly different from the no-PB group in terms of the trends in graft function (estimated glomerular filtration rate). The Kaplan-Meier curve showed that PB did not significantly improve graft or overall patient survival. However, in the multivariate Cox analysis, the double PB group had advantages in graft survival, CKD progression, and new-onset CKD. PB can play a protective role in the maintenance of kidney grafts in kidney transplant recipients., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The aim of this study was to determine the appropriate body mass index (BMI) in Japanese kidney transplant (KTx) recipients. We analyzed the effects of pre- and post-transplant (Tx) obesity on graft and patient survival, perioperative complications, post-transplant diabetes mellitus (PTDM), and cardiovascular disease (CVD) in Japanese KTx recipients., Methods: This retrospective study included 269 recipients who underwent KTx from 2008 through 2020 at Niigata University Hospital. Obesity was defined as a body mass index (BMI) ≥25 kg/m 2 . We examined the association between pre- and post-Tx obesity and graft survival, patient survival, the incidence of PTDM and CVD, and perioperative surgical complications., Results: The graft survival rate was lower in the pre-Tx BMI ≥25 kg/m 2 group, although there was no significant difference in patient survival. There was no difference in graft and patient survival between the post-Tx BMI ≥25 kg/m 2 group and the <25 kg/m 2 group. A pre-Tx BMI ≥25 kg/m 2 was an independent risk factor for biopsy-proven allograft rejection. New-onset DM after transplantation was significantly more common in the BMI ≥25 kg/m 2 group than in the BMI <25 kg/m 2 group (36% vs 13%; P = .002). The incidence of CVD was significantly higher in the post-Tx BMI ≥30 kg/m 2 group than in the BMI <30 kg/m 2 group (50% vs 11%; P = .023). There were no differences in surgical operating time, intraoperative blood loss, or perioperative complications between the obese and non-obese groups., Conclusion: Pre-Tx BMI ≥25 kg/m 2 may be a risk factor for allograft rejection and graft loss. Post-Tx BMI should be <25 kg/m 2 to reduce the risk for PTDM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The liver is considered the most immunotolerant organ among all solid-organ transplants. Liver transplant recipients have a lower incidence of rejection and better outcomes after episodes of rejection, with spontaneous operational tolerance developing in up to 20%. In multiorgan transplants, a protective effect of the liver allograft on simultaneously transplanted organs from the same donor has been demonstrated. We describe an unusual case of isolated liver allograft rejection in a patient with polycystic liver and kidney disease who received a combined liver-kidney transplant from the same donor. After initial discharge from the hospital, our patient had 2 episodes of biopsy-proven late acute cellular rejections, despite higher levels of immunosuppression required for her kidney allograft, which were addressed with pulsed steroid therapy. She had no evidence of ischemic cholangiopathy on imaging. Later, a subsequent liver biopsy demonstrated features consistent with chronic ductopenic rejection. She was eventually listed for liver retransplant and has recently received a second liver transplant while continuing to have no concerns with her kidney allograft function. Examination of the explanted liver confirmed graft loss from chronic ductopenic rejection. The exact reasons why our patient developed acute graft rejection progressing to chronic end-stage rejection of the liver allograft despite not developing graft rejection in the kidney allograft from the same donor remains elusive. Our experience demonstrates that graft tolerance in multiorgan transplant recipients can be organ specific and despite the belief of "immunologic privilege," isolated liver allograft rejection can occur in multiorgan transplant, resulting in graft loss., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: There is a dearth of data regarding the consequences of ABO-incompatible kidney transplant (ABOiKTx) among post-COVID-19 candidates., Methods: The study was designed as a retrospective, multicentric cohort study across 11 sites in India, from August 2020 to December 2021. The data for ABOiKTx conducted for post-COVID-19 candidates were investigated. The primary outcome of biopsy-proven acute rejection was compared with the ABO protocol implemented through Kaplan-Meier analysis. The secondary outcomes were graft loss, patient survival, and infections., Results: A total of 38 ABOiKTx with candidates of median (interquartile range) age of 38.5 (31.25-47.5) years were performed. Nineteen cases had mild COVID-19 severity, while 9 cases (23.6%) had an oxygen requirement. Six (15.7%) donors also were post-COVID-19. The most common ABO incompatibility reported was A to O in 14 (36.8%) pairs followed by B to O in 10 (26.3%) pairs. The maximum isoagglutinin titer cutoff was 1:2048 and 1:64 for baseline and pretransplant levels, respectively. The median time from COVID-19 infection to surgery was 130 (63.2-183) days. Biopsy-proven acute rejection, graft loss, and mortality were 13.1%, 2.6%, and 2.6%, respectively. The Breslow-Wilcoxon's P value in Kaplan-Meier plots were 0.57 and 0.93 for thymoglobulin-based induction and high dose rituximab-based regimen, respectively. The incidence of reinfection was 2.6%. Two (5.2%) urinary tract infections were reported. No cytomegalovirus or BK polyomavirus infection was reported. The median serum creatinine at 1 year of follow-up was 1.1 (0.8-1.3) mg/dL., Conclusions: Our report implies that ABOiKTx in post-COVID-19 candidates can be successfully performed with no major deviation from standard ABO protocol., (Copyright © 2022. Published by Elsevier Inc.)

Background: During the 1900s, tacrolimus became the mainstay immunosuppressive agent to prevent rejection after kidney transplant. Subsequently, an extended-release tacrolimus (ER-Tac) formulation was developed to improve adherence, and its generic version has been marketed over the last years. This study examines the differences in efficacy and safety between the generic ER-Tac (Conferoport) and the reference brand-name drug (Advagraf)., Methods: Prospective, randomized and parallel single-center study (May 2020 to June 2021) with 52 kidney transplant recipients who were randomly assigned to 1 of the following groups: study group (Conferoport, n = 31) and control group (Advagraf, n = 21). The variables of interest were collected and analyzed to compare tacrolimus efficacy and safety between them. Demographic characteristics of the patients and clinical donor data were homogeneous in both groups (P > .05)., Results: No statistically significant differences were found among treatments regarding dosage used, levels, creatinine, and proteinuria (P > .05), with these variables presenting a downward trend during follow-up and, consequently, the improvement of graft function. Analyses also revealed the absence of differences concerning the incidence of acute rejection and intrapatient variability (coefficient of variation) throughout the first year of evolution between both formulations (P > .05). A total of 5 graft losses occurred, 2 resulting from patient death., Conclusions: In our experience, we found no significant differences between the measured parameters in relation to the efficacy and safety profile of both drugs, with generic ER-Tac being an alternative comparable with the reference brand-name ER-Tac., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The assessment of class II eplet mismatch load is useful to determine the risk of chronic rejection in solid organ transplantation. However, high-resolution (2-field) HLA typing is mandatory to accurately define eplet mismatches. The imputation of the most frequent allele has been used in retrospective studies. Here, we sought to investigate the concordant of antibody-verified (AbV) eplet load in different class II alelles between real 2-field HLA typing and HLA imputed by most frequent allele in a large White cohort., Materials and Methods: The allelic frequency of the different HLA class II loci was calculated using a database of high-resolution typing of 23,628 voluntary Spanish bone marrow donors obtained from the Spanish Registry of Bone Marrow Donors, managed by the Josep Carreras Foundation. The AbV eplet count in the different class II alleles was performed using the HLA-Matchmaker v3.1 algorithm., Results: The probability of imputing the correct allele compared to the most frequent for DRB1 and DQB1 loci was 69.3% and 53.0%, respectively. However, studying the less frequent alleles, the same AbV eplet load was observed in 82.22% and 76.15%, respectively., Conclusions: Our data show that despite the potential error in the imputation of class II HLA typing, the number of AbV eplets is not significantly over- or underestimated in our population. Until high-resolution typing is widely established for solid organ transplantation, retrospective studies of AbV eplet mismatch load with imputed high-resolution types provide an acceptable outcome in White people., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Acute rejection is a risk factor for the development of chronic lung allograft dysfunction, the leading cause of morbidity and mortality in lung transplant recipients. Calcineurin inhibitors are the cornerstone of immunosuppression regimens after lung transplantation., Methods: We retrospectively evaluated the association of tacrolimus level variability with total acute rejection score at 12 months post-transplant. Secondary outcomes included the development of chronic lung allograft dysfunction and antibody-mediated rejection at 24months post-transplant. There were 229 lung transplant recipients included., Results: The mean (standard deviation) total rejection score of the cohort was 1.6 (1.7). Patients with high tacrolimus variability at 0 to 3, 3 to 6, and 6 to 12 months on average scored 0.18 (mean 1.6 vs 1.5; 95% CI): -0.3 to 0.66, P =.46), 0.14 (mean 1.7 vs 1.5; 95% CI: -0.32 to 0.6, P = .55), and 0.12 (mean 1.6 vs 1.5; 95% CI: -0.34 to 0.58, P = .62) point higher in 12-month total acute rejection scores, respectively; however, these differences were not statistically significant. The incidences of chronic lung allograft dysfunction and antibody-mediated rejection were numerically greater in the high variability group throughout certain periods; however, this was not consistent throughout all study timeframes and statistical significance was not evaluated., Conclusions: High tacrolimus variability was not associated with increased 12-month total acute rejection score. Further studies are needed to assess long-term outcomes with tacrolimus level variability., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Induction immunosuppression is used to reduce the incidence of acute rejection and prevent delayed graft function. The 2 rabbit anti-thymocyte globulins- thymoglobulin and Grafalon (ATG Fresenius) have been commonly used for induction immunosuppression and treatment of acute rejection in solid organ transplantation. There are very few studies comparing the efficacy and side effects of both the anti-thymocyte globulins therefore this prospective study comparing the 2 types of anti-thymocyte globulins would be of clinical interest., Patients and Methods: This prospective single center study was conducted at Rabindranath Tagore International Institute of Cardiac Sciences, Kolkata, India from April 2019 to June 2020. Sixty-two ABO-compatible renal transplant recipients were included in the study. They were divided in 2 groups of 31 patients each. One group received thymoglobulin (3 mg/kg) and the second group received Grafalon (6 mg/kg). All patients were followed up for 12 months and the 2 groups were compared for incidence of rejections, infections, graft function, patient survival, and graft survival., Results: There was no significant difference in the incidence of rejections, infective episodes, graft function, posttransplant diabetes mellitus, graft survival and patient survival in thymoglobulin or Grafalon groups. The hematological parameters were similar in both groups at 7 days, 1 month, and 6 months of follow-up. The absolute lymphocyte count was significantly lower in the thymoglobulin group at 12 months posttransplant., Conclusions: Thymoglobulin and Grafalon were found to be equivalent in terms of safety and efficacy in short term, with no difference in rejections, infections, graft survival, or patient survival., Competing Interests: Disclosure All the relevant data has been represented in the manuscript. Any additional data can be provided by corresponding author on reasonable request., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Delayed graft function (DGF) is an important prognostic indicator after kidney transplantation. Depending on the severity of the ischemia-reperfusion injury, DGF can have several clinical presentations, with different renal function recovery times. Both the presence and duration of DGF can have an impact on kidney transplantation outcomes. However, the definition of the cutoff point, above which the outcomes are worse, varies widely in the literature., Methods: To investigate the impact of DGF and its duration on patient and graft survivals, a single-center retrospective study including all deceased donor kidney transplants was performed between November 2008 and December 2015 (n = 188). Through the analysis on the receiver operating characteristic curve, the cutoff point that determined the worst outcome was reached. DGF patients were then divided according to the duration of DGF (<8 days or ≥8 days)., Results: The overall incidence of DGF was 62.2%. Higher HLA mismatches was an independent risk factor for prolonged DGF. DGF ≥8 days was associated with acute rejection and this one was associated with patient death in 3 years., Conclusion: DGF with a duration of more than 8 days associated with higher HLA mismatches increases the risk of acute rejection, but graft loss and patient survival are not affected by DGF, regardless of its duration., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Long-term results of kidney transplant (KTx) in older patients may differ from younger recipients owing to increased cardiovascular comorbidities. The study aimed to analyze surgical and nonsurgical complications that develop in the long-term follow-up period after KTx, and factors that influence results of KTx in recipients aged 60 years and older (≥60) compared with younger recipients (<60)., Methods: One hundred seventy-five patients aged ≥60 years and 175 patients aged <60 years who received a kidney graft from the same deceased donor were enrolled in the study. In the long-term follow-up period (3 months to 5 years after KTx) the incidence of surgical and nonsurgical complications, as well as patient and kidney graft survival, were compared. Additionally, the influence of early complications on patients and kidney graft survival was assessed., Results: There were no differences between recipients aged ≥60 years compared with recipients aged <60 years in occurrence of surgical complications (graft artery stenosis: 0.6% vs 2.3%; ureter stenosis: 3.4% vs 1.1%; lymphocele: 6.9% vs 3.4%) and nonsurgical complications (urinary tract infection: 19.4% vs 23.4%; pneumonia: 8.6% vs 8.6%; cytomegalovirus infection: 6.3% vs 8%; new-onset diabetes after transplant: 16.6% vs 17.1%; cancer incidence: 5.7% vs 4.6%; acute rejection episode: 13.1% vs 17.1%). Five-year recipient survival was lower in a group of patients aged ≥60 years (death, 15.4% vs 8%; death with functioning graft, 12% vs 5.1%)., Conclusions: The incidence of surgical and nonsurgical complications, as well as kidney-graft survival, in recipients aged ≥60 years in a 5-year follow-up period is comparable to younger recipients aged <60 years., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Acute kidney injury (AKI) is common after liver transplantation (LT). Induction with interleukin-2 receptor antagonists is often used as a "renal-sparing" strategy. The aim of this study was to assess this approach in a real-world setting in an LT center., Methods: A retrospective cohort analysis of LTs between 2011 and 2018 was performed to assess the impact of a renal-sparing strategy using basiliximab in conjunction with mycophenolate mofetil and corticosteroids from day 0 post-LT along with delayed introduction of tacrolimus. This was compared with a group receiving tacrolimus, mycophenolate mofetil, and corticosteroids from the outset., Results: The renal-sparing regimen was associated with significantly lower incidence of all-stage AKI at day 7 post-LT (36% vs 55%, P = .006) and less decline in renal function at 3 months (39% vs 57%, P = .01). No further significant differences in renal outcomes were observed at other time points on follow-up to 1 year post-LT. There was no significant difference in the incidence of acute cellular rejection, inpatient length of stay or graft survival. The decision to adopt a renal-sparing regimen was predominantly made on a clinically reactive basis within the first 24 hours post-LT in 77%, and was preordained in 23%. Cost-effectiveness analysis did not find evidence of a significant cost saving when using a renal-sparing strategy., Conclusion: This study provides real-world analysis of the use of a renal-sparing immunosuppression regimen in LT. Although improvements in incidence of AKI in the short term were demonstrated, this did not translate to cost savings or improved renal outcomes after 3 months., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Delayed graft function (DGF) is a frequent complication after kidney transplantation affecting long-term outcome., Patients and Methods: A total of 525 consecutive recipients (age 54.2 ± 13.4 years, 33% female) of kidneys from deceased donors transplanted between 2005 and 2012 were retrospectively examined. DGF was defined as the need of dialysis within the first week after transplantation., Results: DGF developed in 21.1% (n = 111). Factors associated with DGF (P ≤ .035, respectively) were recipient body mass index, C-reactive protein of the recipient, residual diuresis, cold ischemia time, donor age, and diuresis in the first hour after transplantation. Median duration of DGF was 16 (2-66) days. Patients after DGF had a significantly lower GFR compared with recipients without DGF either after 3 (32.9 ± 16.5 vs 46.3 ± 18.4 mL/min/1.73 m 2 ) or after 12 months (38.9 ± 19.3 vs 48.6 ± 20.4 mL/min/1.73 m 2 , P < .001, resp.). During DGF, 12.4% developed BANFF II and 18.0% BANFF I rejection, 20.2% had signs of transplant glomerulitis (first biopsy), and 16.2% (n = 18) remained on dialysis., Conclusion: DGF affects 1 out of 5 kidney transplants from deceased donors. Minimizing modifiable risk factors, in particular immunologic risk, may ameliorate the incidence and outcome of DGF. The outcome of DGF depends mainly on the diagnosis of any rejection and worsens upon detection of transplant glomerulitis and pronounced interstitial fibrosis and tubular atrophy (IFTA)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Percutaneous endomyocardial biopsy (EMB) remains the criterion standard method for surveillance of allograft rejection after heart transplant (HT). However, data regarding utility of EMBs and prevalence of acute cellular rejection (ACR) in Asian populations are still limited. We aimed to report our experience in the use of EMBs and prevalence of ACR in HT recipients., Methods: We retrospectively evaluated all EMBs from consecutive HT recipients between January 2008 and December 2018. EMB pathology results were according to International Society for Heart and Lung Transplantation 2004 revision of biopsy grading. We also divided patients into previous era and current era group (underwent HT before and after 2015) to compare prevalence of ACR and survival outcome., Results: A total of 832 EMBs from 81 HT recipients were included. Pathologic reports revealed ACR grade 1R 22.8%, 2R 4.2%, and 3R 0.6%. At patient level, at least 1 episode of ACR grade 1R, 2R, and 3R were found in 70.6%, 24.7%, and 3.5% of the patients, respectively. When compared between era, frequency of EMB during the first year after HT in current era was significantly higher (9.74 ± 3.38 vs 4.93 ± 3.29, P < .001), but lower frequency of rejection grade ≥ 2R were found (2.3% vs 8.1%, P < .001). However, 1-year survival was not statistically different (76% in previous era vs 80% in current era, P = .37)., Conclusions: From our study, prevalence of grade ≥ 2R rejection was approximately 5%, which is comparable with previous studies. Further studies are needed to evaluate proper interval and number of EMBs in HT recipients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Tacrolimus and mycophenolic acid (MPA) are the most important immunosuppressive drugs in modern heart transplantation. The pharmacokinetics of tacrolimus are best described by a 2-compartment model. MPA has very variable pharmacokinetics. The aim of this research was to compare kinetics of the immunosuppressants' blood levels in a group of patients with and without graft rejection., Materials and Methods: The study was a retrospective analysis of 39 consecutive adult orthotopic heart transplantations (OHT): 10 (9 men and 1 woman) in group R had graft rejection (ISHLT >2) in the first biopsy and 29 (22 men and 7 women) in group C were without rejection. Ischemic cardiomyopathy occurred in 2 of 7 and nonischemic cardiomyopathy in 8 of 22 (group R and group C, respectively)., Results: Patients did not differ between groups except diabetes, which occurred more often in group R. Immunosuppressive drug levels were: group R and group C, respectively, 2.13 ± 0.49 and 2.11 ± 0.72 μg/mL; P = .93 for mycophenolate mofetil (MMF) and 9.42 ± 1.76 and 9.63 ± 2.30 ng/mL; P = .75 for tacrolimus. ICU stay was 14 ± 11 vs 15 ± 15 days; P = .76. There were 2 of 6 primary graft failures, 1 of 1 neurologic complications, and 0 of 6 reoperations (P < .05) in group R and group C, respectively. One patient died from group C in 30 days. During the hospital stay the incidence of graft rejection was diagnosed in 20 patients (16men and 4 women) (ISHLT >2 in endomyocardial biopsy) in the study population., Conclusions: Monitoring of tacrolimus concentration in the early post--heart transplant period does not identify patients with rejection in the authors' study. Monitoring concentration of MMF does not identify patients with rejection. Further investigation is needed to evaluate factors responsible for post--heart transplant rejection in the early phase., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Renal transplantation is the treatment of choice in end-stage renal disease. With the aging of the population and better medical care available, the number of high-risk patients in terms of age and comorbidities on transplant waiting lists is increasing. Due to severe organ shortage, the use of expanded criteria and elderly donors is also increasing. We will review the outcomes of graft function and survival from a series of transplants from elderly deceased donors and compare the characteristics of the organs from donors older and younger than 70 years., Methods: We collected data from our transplant unit from 1993 until May 2019 and considered 2 groups of donors: donors A (aged ≥70 years) and donors B (aged <70 years)., Results: The donors A group had more comorbidities with consequently higher Kidney Donor Profile Index scores than the donors B group, although there was no statistical difference regarding pre-donation serum creatinine level. Among transplant recipients, we also considered 2 groups, according to the age of the organ received: recipients A and recipients B. No difference was found between groups regarding the number of HLA mismatches, incidence of delayed graft function, number of hospitalizations, or incidence of acute rejection. Recipients' age, cold ischemia time, and graft function 1 year after transplant were worse in the recipients A group., Conclusions: Although kidney graft function was worse in recipients from elderly donors, this difference had no clinical relevance, showing a possible benefit in patient survival compared with permanence in dialysis, so this type of transplant could be considered for older recipients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Transbronchial biopsy (TBB) using standard forceps is the main procedure to establish the presence of lung allograft rejection (AR) after lung transplantation. Few studies report the use of the transbronchial cryobiopsy (TCB) as a scheduled procedure for surveillance purposes in lung allograft, despite this the technique yields larger biopsies. We aimed to analyze the diagnostic yield and potential complications of TCB compared with conventional forceps biopsy for acute rejection surveillance in lung transplantation. In our center, TCBs are performed to monitor lung allografts at 3, 6, and 12 months after transplantation. From March 2018 to September 2019 TCBs were performed in 54 lung transplanted patients for surveillance purposes. Clinical and functional data, complications, and histologic results were collected. We analyzed through a retrospective study our first 75 cases of cryobiopsies for surveillance purposes in lung allograft recipients. The diagnostic rate of AR using TCB was 100% compared with 83% using conventional TBB. Also, diagnostic rate of airway inflammation and chronic rejection was 17% and 21% higher, respectively, for TCB compared with TBB. The overall major complication rate was 9%: 1 pneumothorax case required chest tube drainage and 6 moderate bleedings. Bleeding rate in the scheduled TCB group (8%) seems to be higher if compared with scheduled TBB group (1%). TCB seems to be safe and effective for diagnosis of lung AR compared with transbronchial conventional forceps biopsy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Urinary tract infection is the most common bacterial infection after kidney transplant. Some studies suggested that urinary tract infection could impair graft survival, but this issue remains debated. The objective of this study was to analyze the association between acute pyelonephritis (APN) and the risk of kidney graft failure., Methods: We performed a retrospective cohort study including patients who received a kidney transplant from 2001 to 2009 at a university hospital in Rio de Janeiro, Brazil. They were followed until December 2015. The primary outcome was graft failure. Follow-up of patients who died with a functioning graft was censored on the date of death. Cox proportional hazards method was used in multivariable analysis to assess risk factors for graft failure. The occurrence of the first episode of APN and acute rejection were modeled as time-dependent variables., Results: A total of 587 patients were included. Of these, 112 recipients (19%) developed 173 episodes of APN. Graft failure occurred in 150 patients (25%) after a median follow-up of 79 months. The factors associated with graft failure in the multivariate analyses were age of the transplant recipient (hazard ratio [HR], 0.97 per year; 95% confidence interval [CI], 0.96-0.99; P < .01), occurrence of delayed graft function (HR, 2.42; 95% CI, 1.72-3.40; P < .01), and acute rejection (HR, 2.71; 95% CI, 1.92-3.82; P < .01). There was no association between APN and graft failure (HR, 1.05; 95% CI, 0.65-1.68; P = .85)., Conclusions: Our results suggest that the occurrence of APN is not associated with a significant reduction in graft survival after kidney transplant., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In the field of transplantation, expression of HLA-G, a nonclassical HLA molecule with immunosuppressive functions and limited gene polymorphism, is considered beneficial for graft acceptance; various studies have aimed to demonstrate this role in transplantation. Recently, in other clinical conditions, it has been observed that insulin resistance was associated with HLA-G14bpins/del polymorphism, the most studied regulatory polymorphism of this molecule. In the present study, plasma levels of the soluble form of HLA-G (sHLA-G) were analyzed in kidney transplant recipients (n = 103) with different HLA-G14bpins/del genotypes. In a group of 26 recipients, sHLA-G was detected before and after transplantation (1 year) to evaluate early variations. In 77 recipients, sHLA-G was detected after transplantation (3-24 years) and correlated with occurrence of long-term post-transplant morbidity (diabetes mellitus, hyperlipidemia, hypertension, obesity, etc.)., Methods: Levels of sHLA-G were measured in plasma with an enzyme-linked immunosorbent assay; HLA-G14bpins/del and HLA-G+3142C>G genotypes were assessed using direct polymerase chain reaction., Results: Plasma levels of sHLA-G significantly decreased during the first year after transplantation (P = .019); no significant correlations were found with genotypes or early post-transplant events. Lower levels of sHLA-G were found in recipients with post-transplant diabetes mellitus or obesity carrying the HLA-G14bpins/ins (P = .006 and P = .003, respectively) or HLA-G+3142G/G genotypes., Conclusions: A complex modulation of HLA-G, which includes both immunologic and metabolic effects, could affect the risk for long-term post-transplant morbidity in kidney transplant recipients. Associations of HLA-G, diabetes, and obesity deserve to be investigated by deeply exploring HLA-G regulatory variants., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The recommended standard immunosuppressive therapy for renal transplant recipients comprises an initial induction therapy mainly with an interleukin-2-receptor antibody (IL2-RA) and a triple maintenance therapy. With tacrolimus and mycophenolate acid it is unknown whether IL2-RA application affects the short- and long-term results. This question is addressed in the present analysis., Methods: From July 2007 to June 2019 a total of 127 living donor kidney transplant recipients meeting the center-specific definition of immunologic low risk situation (first transplantation, HLA-mismatch ≤3, panel reactive antibody ≤10%) were identified. In 83 recipients with a first-degree relationship to the donor we omitted the IL2-RA induction (IL2-RA-). The remaining 44 recipients, mostly not first-degree relatives, served as controls (IL2-RA+). Biopsy-proven acute rejection and long-term patient and graft survival rates were compared., Results: Biopsy-proven acute rejection rates after 3 months were similar in both groups with 4.8% (IL2-RA-) vs 13.7% (IL2-RA+; P = .0937), including borderline rejection rates of 18.0% (IL2-RA-) vs 18.3% (IL2-RA+; P = 1.000), respectively. Ten-year long-term survival rates were comparable between the IL2-RA- and the IL2-RA+ group with 95.6% vs 93.5% (patient survival; P = .5465) and 92.1% vs 90.6% (death-censored graft survival; P = .8893)., Conclusion: For low-risk living donor kidney transplant recipients with first-degree relationship to the donor, it is safe to omit induction therapy with IL2-RA., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The lowering of calcineurin inhibitor exposure is possibly considered as the proper strategy to prevent calcineurin inhibitor-induced nephrotoxicity in kidney transplant. This clinical study was designed to compare the efficacy and tolerability of reduced-dose tacrolimus with standard-dose mycophenolate mofetil (MMF) vs standard-dose tacrolimus with reduced-dose MMF., Methods: A prospective, multicenter, open-label, randomized, and parallel-group clinical trial was conducted at 4 transplant centers in Korea. A total sample size was 108, and eligible patients were randomly assigned in a 1:1 ratio to either reduced-dose tacrolimus with standard-dose MMF (the study group) or standard-dose tacrolimus with reduced-dose MMF (the control group) for 6 months in de novo kidney transplant recipients. Graft function, the incidence of efficacy failure, and adverse events were compared., Results: The mean estimated glomerular filtration rate at 6 months post-transplantation was 69.83 ± 16.68 mL/min/1.73 m 2 in the study group and 69.92 ± 17.55 mL/min/1.73 m 2 in the control group (P > .05). The overall incidence of biopsy-proven acute rejection was 3.64% (n = 2) in the study group, compared to 3.77% (n = 2) in the control group (P > .05). There was no graft loss, death, or loss of follow-up in either group., Conclusion: In conclusion, the results suggest that tacrolimus minimization with standard-dose MMF provides adequate immunosuppression with proper renal function and similar rate of incidence of acute rejection compared with the regimen including standard-dose tacrolimus with reduced-dose MMF., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Hyperlipidemia and cardiovascular disease are risk factors for long-term renal transplant dysfunction. However, no meta-analyses of randomized controlled trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effects of statin use on renal transplant patients using a meta-analysis approach., Methods: We conducted a systematic review and meta-analysis using random effects modeling. We searched the following databases for all studies published through to June 15, 2018: Cochrane Central Register, OVID MEDLINE, Embase, and PubMed. We reviewed all relevant reviews, registered trials, and relevant conference proceedings to compare clinical outcomes and survival between fluvastatin recipients and controls., Results: Five trials with a total of 3725 patients were included. Glomerular filtration rates, graft loss, tacrolimus level, antibody-mediated rejection, T cell-mediated rejection, proteinuria, fungal infection (candida), and patient survival rates did not differ between the fluvastatin and control groups. However, major adverse cardiovascular events were 1.547 times more common in the control group than in the fluvastatin group (P = .001)., Conclusions: Fluvastatin use was associated with a reduction in major adverse cardiac events among kidney transplant patients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: This study aims to analyze the entire registry of kidney transplant over the past 50 years and understand the clinical significance., Methods: From the data on 3012 kidney transplants performed at our center between March 1969 and September 2018, we analyzed retrospectively clinical variables., Results: Until September 2018, there have been 3012 kidney transplants performed. The number of primary transplant cases was 2755 (91.8%), which included 16 cases of simultaneous liver-kidney transplant, and the number of repeated transplants was 245 (225 second transplants [7.5%] and 20 third transplants [0.7%]). There were 3 simultaneous pancreas kidney transplants, and 3 small bowel-kidney transplants, one of them being transplanted at the same time. There was a single simultaneous heart-kidney transplant. The viability rates of a transplanted kidney for 1, 5, 10, 20, and 30 years were 97%, 92%, 90%, 51%, and 36%, respectively, and the patient survival rates were 96%, 89%, 82%, 64%, and 52%, respectively. Five-year graft survival rate of the first 1000 cases was 64.6%; those of the 1001st to 2000th cases and 2001 st to 3012th cases were 87.6% and 88.8%, respectively. There are statistically significant differences among the groups., Conclusion: This study has identified the appropriate selection or control of immunotherapy, based on the risk level of kidney transplant recipient, is needed to minimize chronic rejection, which is the key cause of transplanted kidney failure., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The clinical benefit of rabbit antithymocyte globulin (Thymoglobulin) compared with basiliximab for induction therapy in kidney transplant (KT) resulting from acute kidney injury (AKI) donors remains controversial. In cases of severe AKI, the degree of kidney injury is too great to reveal influence of different induction therapies on clinical outcomes. We aimed to compare clinical outcomes of Thymoglobulin and basiliximab induction therapy in KTs from deceased donors (DDs) with mild to moderate AKI., Methods: We retrospectively studied 147 patients who received KTs from DDs between 2009 and 2017 in our center; 91 patients received kidneys from AKI donors. The AKI severity was classified based on the Acute Kidney Injury Network (AKIN) staging, and patients with AKIN stage 3 (43 patients) were excluded. Clinical outcomes were compared according to the type of induction therapy., Results: Thymoglobulin and basiliximab induction groups showed no significant differences in demographic and baseline characteristics except donor age and follow-up period. The Thymoglobulin group had lower incidences of acute rejection and a trend toward a lower incidence of delayed graft function and better graft survival than the basiliximab group. There was no significant difference in BK infection rate; however, cytomegalovirus infection rate showed a trend toward a lower incidence in the basiliximab group., Conclusions: In cases of KT from AKIN stage 1 and 2 donors, Thymoglobulin showed better clinical outcomes than basiliximab, although it had a somewhat high rate of cytomegalovirus infection. It seems beneficial to use Thymoglobulin induction therapy in KTs from DDs with mild to moderate AKI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The stable immunosuppressant level at the early period after kidney transplantation (KT) is one of the most important factors for the prognosis of KT. However, the extent of immunosuppression varies according to the policies of each KT center. We investigated the relationship between the clinical outcome and tacrolimus trough level (TTL) at the early post-transplant period., Materials and Methods: We retrospectively analyzed medical records of patients who underwent KT between July 2007 and June 2016. We investigated TTLs at 3 months after KT. We evaluated the incidence of biopsy-proven acute rejection (BPAR), cytomegalovirus infection, and graft survival according to the TTLs., Results: A total of 426 patients who received KT during the study period were enrolled. The mean age of KT recipients was 46.3 ± 11.5 years, and 55.5% of patients were men. The incidence of BPAR within 1 year after KT was significantly higher when TTLs at 3 months were less than 4.0 ng/mL (P = .020). Death-censored graft survival rates were significantly lower in KT recipients with BPAR and TTL less than 4.0 ng/mL (P < .001, P < .001, respectively). In multivariate analysis, BPAR and TTL less than 4.0 ng/mL at 3 months after KT were independent risk factors for graft failure., Conclusion: BPAR and TTL less than 4.0 ng/mL at 3 months after KT are important risk factors for allograft failure. Therefore, TTL should be kept at least 4.0 ng/mL or more at 3 months after KT to reduce the incidence of BPAR within 1 year after KT., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: The need for donor pool expansion remains an important task for kidney transplantation. The aim of this study is the evaluation of primary nonfunction (PNF) from donation after circulatory death (DCD) kidneys., Methods: Between 1996 and 2017, 100 kidney transplants from DCD donors were conducted in our department. We retrospectively analyzed PNF of kidney transplant recipients from DCD donors in terms of donors' and recipients' epidemiologic characteristics., Results: Of 100 grafts, 95 recipients (95.0%) had discontinued hemodialysis at the time of hospital discharge. Only 5 recipients (5.0%) developed PNF. All 5 PNF recipients received a single graft from an expanded criteria donor (ECD). The mean donor age in the PNF group was 65.0 (SD, 6.2) years. Significant differences between the PNF group and discontinued dialysis group were found for donor age (P < .01) and for the use of ECD kidneys (P < .02). Nevertheless, no significant difference was found between groups for several factors: a history of hypertension and cerebrovascular events, terminal creatinine levels, and graft weight., Conclusion: The incidence of PNF from DCD kidneys was very low. Although ECD kidneys in older donors might be a significant risk factor for PNF, these findings suggest that DCD kidneys should be used more frequently for donor expansion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Despite advances in immunosuppressive drugs, postoperative care, and surgical techniques, bacterial infections remain the most important cause of morbidity and mortality in liver transplant patients. The aim of this study is to evaluate the influence of culture results taken on the first day of admission to intensive care unit on mortality, graft rejection, mechanical ventilation duration, and length of intensive care unit stay. Our study has clinical importance because it is the first study evaluating the cultures obtained on the first day of intensive care unit stays in liver transplant patients., Methods: Patients' demographic data, transplant type, rates of deceased and living donors, culture results, amount of blood and blood products used intraoperatively, previous hospital admission, mortality, incidence of graft rejection, mechanical ventilation duration, and length of intensive care unit stay were recorded., Results: Mortality and graft rejection were 14.8% and 9%, respectively. The mortality was significantly higher in all 3 cultures and/or in only blood culture-positive patients. Graft rejection, mechanical ventilation duration, and length of intensive care unit stay were significantly higher in patients whose 3 cultures were all positive. Only body mass index had a significant effect on mortality, graft rejection, and positive culture results., Conclusions: Liver transplant patients' first postoperative day culture results were correlated with mortality, graft rejection, mechanical ventilation duration, and length of intensive care unit stay., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Amyloid A amyloidosis is most commonly caused by familial Mediterranean fever (FMF) in Turkey. Amyloidosis secondary to FMF is an important cause of end-stage renal failure, and kidney transplantation (KT) in these cases can be complicated, with long-term results oftentimes inferior compared with organ transplant in patients without FMF. The present study aims to show the long-term results of patients with secondary amyloidosis caused by FMF undergoing KT ., Methods: We enrolled 27 patients with a history of FMF amyloidosis undergoing KT and a control group of 614 patients undergoing KT between 2005 and 2018 at Ankara University Medical School. All data were recorded retrospectively from patients files., Results: Twenty-two patients (81.5%) were treated with triple immunosuppressive therapy consisting of mycophenolate mofetil, tacrolimus, and a steroid; 5 patients (18.5%) were treated with tacrolimus, azathioprine, and prednisolone. Acute cellular rejection was seen in 3 patients (11.1%), and acute cellular- and antibody-mediated rejection occurred in 1 patient (3.7%). During the follow-up period, graft loss due to acute cellular rejection was observed in only 1 patient. One patient was lost to follow-up., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Lifelong adherence with post-transplant immunosuppression is challenging, with nonadherence associated with greater acute rejection (AR) risk., Methods: This retrospective study evaluated conversion from immediate-release tacrolimus (IRT) to prolonged-release tacrolimus (PRT), between January 2008 and December 2012 in stable adult heart transplant recipients. Cumulative incidence rate (IR) of AR and infection pre- and postconversion, safety, tacrolimus dose and trough levels, concomitant immunosuppression, and PRT discontinuation were analyzed (intention-to-treat population)., Results: Overall, 467 patients (mean age, 59.3 [SD, 13.3] years) converted to PRT at 5.1 (SD, 4.9) years post transplant and were followed for 3.4 (SD, 1.5) years. During the 6 months post conversion, 5 patients (1.1%; 95% CI, 0.35%-2.48%) had an AR episode and IR was 2.2/100 patient-years (95% CI, 0.91-5.26). Incidence of rejection preconversion varied by time from transplant to conversion. Infection IR was similar post- and preconversion (9.2/100 patient-years [95% CI, 7.4-11.3] vs 10.6/100 patient-years [95% CI, 8.8-12.3], respectively; P = .20). Safety variables remained similar post conversion. The IR of mortality/graft loss was 2.3/100 patient-years (95% CI, 1.7-3.1)., Conclusions: Conversion from IRT to PRT in heart transplant recipients in Spain was associated with no new safety concerns and appropriate immunosuppressive effectiveness., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although tacrolimus is an effective immunosuppressive drug used for preventing biopsy proven acute rejection (BPAR) in kidney transplanted patients, its nephrotoxicity may compromise renal function and lead to delayed initiation because of its side effects. This study aimed to evaluate the safety of early initiation of tacrolimus in the occurrence of BPAR during the first 90 days post transplant., Methods: We conducted a retrospective cohort study involving 315 patients who underwent kidney transplantation from 2015 to 2017. Comparisons were performed between 2 groups according to whether the start time of tacrolimus therapy was delayed or not delayed. Cox proportional hazards models were used to examine the association between variables and the occurrence of BPAR., Results: The incidence of BPAR was 14.9% (n = 47) and it was significantly higher in the delayed group (19.4% vs 6.4%; P = .002). Delayed initiation tacrolimus group was significantly associated with the risk of BPAR (hazard ratio: 2.95; P < .036). The overall mortality rate was 2.5% (n = 8) and there was no association between delayed initiation therapy and death (P = .56)., Conclusion: Our study confirmed that delayed initiation of tacrolimus in patients with delayed graft function is associated with a high risk of BPAR., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Lung transplantation is a well-established treatment for selected patients with advanced cystic fibrosis (CF)- and non-cystic fibrosis (non-CF)--related bronchiectasis. Because the number of lung transplants performed for patients with non-CF bronchiectasis is much smaller than for patients with CF, little data is available regarding patient selection, choice of procedure, and outcomes., Methods: Between November 1997 and December 2013, 42 patients with CF and 33 patients with non-CF bronchiectasis underwent lung transplantation at the Rabin Medical Center, Israel. We analyzed and compared pretransplant evaluation data and short- and long-term results in both groups., Results: Median survival for the CF group in our study was 8.4 years, compared with 7.1 years for the non-CF group (P = .098), similarly to that reported by the International Society for Heart and Lung Transplantation Registry data. The main survival difference between groups was in the early postoperative period. Both groups achieved similar peak forced expiratory volume in 1 second values and had stable lung function at the 3-year follow-up. Biopsy-proven rates of acute cellular rejection were low for both groups. Rates of chronic lung allograft dysfunction development did not differ between CF and non-CF recipients., Conclusion: Our institutional experience confirms that lung transplantation is feasible for non-CF bronchiectasis, and results are comparable to our CF cohort. The increased early mortality in this study occurred from 1999 to 2008 and was probably related to surgical techniques used at the time. Overall, 3-year and 5-year survival were comparable with the International Society for Heart and Lung Transplantation Registry data. Non-CF bronchiectasis patients achieved and maintained satisfactory lung function., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Following liver transplantation (LT), the majority of patients are treated with reduced-dose calcineurin inhibitors (CNIs) in combination with mycophenolate mofetil. The optimal timing for subsequent conversion to CNI monotherapy is not clearly defined. This study aims to evaluate the safety of conversion to CNI monotherapy after LT., Methods: This was a single-center retrospective study of 100 consecutive patients who received CNI and mycophenolate mofetil combination regimen after LT at Singapore General Hospital from 2006 to 2018. Patient demographics, clinical parameters, and posttransplant complications (ie, rates of graft rejection, de novo malignancy, cytomegalovirus infection and renal impairment) were recorded., Results: One hundred patients were recruited and mean follow-up time in months ± standard deviation was 60.36 ± 41.73. Patients were divided into 2 groups based on institution of CNI monotherapy within (group 1) or beyond (group 2) 6 months. Twenty-five (25%) patients were on CNI monotherapy within 6 months post-LT. Overall patient survival was 83.7% at 5-years posttransplant. There was no statistical difference in the rates of posttransplant complications including liver graft rejection (4.0% vs 18.7%, P = .11); de novo malignancy (0.0% vs 8.0%, P = .33); cytomegalovirus infection (4.0% vs 1.3%, P = .44); and renal impairment (20.0% vs 40.0%, P = .069) between the 2 groups., Conclusions: Successful institution of CNI monotherapy within 6 months is safe, and does not increase the risk of rejection., (Copyright © 2019. Published by Elsevier Inc.)

Background: The diagnostic criteria of antibody-mediated rejection (ABMR) has been significantly changed since Banff 2013. The most important revision was adopting microvascular inflammation (MVI) as immunopathologic evidence for ABMR even in C4d-negative cases. In this study, we retrospectively reviewed previous allograft biopsy results and evaluated the impact of this change., Methods: We reviewed results of 536 renal allograft biopsies at Severance Hospital during 2011 to 2013, which were diagnosed according to the Banff 2009 criteria. All biopsy results were reassessed according to the Banff 2017 criteria., Results: According to the Banff 2009 criteria, antibody-mediated changes were observed in 48 cases out of the 536 allograft biopsies (9.0%). According to the Banff 2017 criteria, 28 additional cases (5.2%) were reclassified as antibody-mediated changes. Twenty-six of these cases were C4d-negative ABMR. The most frequent diagnostic finding in these cases was MVI comprising glomerulitis and peritubular capillaritis. Donor-specific antibodies were investigated in 14 of these cases, which revealed positive results in 12 cases., Conclusion: The incidence rate of ABMR has increased after the recent revision of the Banff criteria. The MVI in C4d-negative ABMR cases is the major cause for this increase., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Superior patient and graft survival rates have been attributed to living donor kidney transplant (LDKT) when compared to deceased donor transplantation. The aim of this study was to assess graft survival in a population of LDKT in the last 14 years and the potential impact of some clinical features., Methods: A retrospective observational study was conducted, reviewing the records of all patients undergoing LDKT in one center from January 1, 2004, to December 31, 2017. Survival data were evaluated by Kaplan-Meier, log rank test, and Cox regression., Results: Two hundred seventy-seven LDKT were performed. The median follow-up time was 4 (0-13) years. Graft loss was observed in 9% of patients; 4 patients died. The overall survival was 97% at year 1, 94% at year 5, and 83% at years 10 and 13. We found a significantly worse graft survival in patients with early vascular complications that required surgical intervention (P = .00) ≥3 HLA MM (P = .01), ≥1 HLA-DR MM (P = .04) and female recipients (P = .01). The negative impact of ≥1 HLA-B MM on survival was borderline (P = .05). After excluding early graft losses secondary to vascular events, ≥1 HLA-A MM and rejection have also implicated a negative impact on survival (P = .04 and .01, respectively). In the multivariate analysis, these variables were still related to inferior survival., Conclusions: We observed a good overall graft survival (>80% after 13 years). Possible factors related to poor outcomes suggested by this study were early vascular complications; HLA mismatches; rejection; and, with less certainty, female recipients., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Our study compares 2 immunosuppressive strategies to reduce tacrolimus nephrotoxicity and its risk of acute tubular necrosis: delayed introduction of tacrolimus plus thymoglobulin vs initial tacrolimus plus basiliximab on the results of kidney transplant (KT) using type-III donation after circulatory death (III-DCD)., Material and Methods: We analyzed all the transplants performed using type-III DCD in our hospital (42 cases). They were distributed in a first stage with delayed tacrolimus (3°-4° day) + thymoglobulin and a second one with initial tacrolimus + basiliximab, with a follow-up of 6 months. The rate of delayed graft function, the evolution of renal function, and the incidence of rejection were compared., Results: 28 patients received thymoglobulin with delayed tacrolimus, and 13 patients received basiliximab and tacrolimus from day 0 (1 excluded). There were no significant differences in delayed graft function (27% group 1 and 23% group 2) or in rejection (10.7% and 15.4%), respectively. Serum creatinine at day 3, 7, 14, 30, and 180 showed no statistically significant differences. The levels of tacrolimus measured at 10, 30, 90, and 180 days after transplantation were similar, except for the first month: 10.10 ± 2.3 in group 1 and 12 ± 1.7 ng/mL in group 2 (P = .007)., Conclusions: Delayed introduction of tacrolimus does not seem to suppose a benefit in KT using type-III DCD; therefore, the use of thymoglobulin, with its higher profile of adverse effects, seems unjustified in patients with normal immunological risk., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In this retrospective single-center study we evaluated the outcome after kidney transplant in recipients older than 65 years in terms of patient and graft survival and causes of death., Patients and Methods: From 1993 to 2016, 109 consecutive first single kidney transplants in recipients older than 65 years were included. Furthermore, 2 age groups have also been identified (group A, 65-70 years old vs group B, 71-76 years old). Donor and recipient characteristics were analyzed. Other parameters were cold and warm ischemia times, delayed graft function, biopsy-proven acute rejection, and causes of death. Induction immunosuppressive therapy was performed with basiliximab or thymoglobulin. Baseline triple immunosuppression included calcineurin inhibitor, antimetabolite, and steroids. The results of preimplantation biopsies, which were performed in all expanded criteria donors were analyzed and graded according to Karpinski 2009 classification., Results: Overall mortality was 39.4%: 23.2% women and 76.8% men. Causes of death were infections in 42%, tumors in 23%, cardiovascular disease in 14%, cerebrovascular disease in 7%, and unknown in 14%. The most common cause of death in men was infections (52%), and the most common cause in women was tumors (55%). At 1, 3, 5, and 10 years, overall patient survival was 89%, 84%, 72%, and 45%, and overall graft survival was 100%, 97%, 89%, and 84%, respectively. Patient and graft survival were statistically different between group A vs group B (P = .006 and P = .02, respectively). At univariate analysis significant risk factors for increased mortality were age, delayed graft function, and cold ischemia time. At multivariate analysis, delayed graft function maintained statistical significance., Conclusions: Kidney transplantation in patients older than 65 years is safe, feasible, and has good graft survival. Mortality is statistically significant in patients older than 71 years, despite a persistent low graft loss., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Objectives: Heart and lung transplantation is a high-risk procedure requiring intensive immunosuppressive therapy for preventing organ rejection. Alemtuzumab, a CD52-specific monoclonal antibody, is increasingly used for induction therapy compared with conventional agents. However, there has been no systematic review comparing its efficacy with traditional therapeutic drugs., Methods: PubMed and EMBASE were searched to October 1, 2017, for articles on alemtuzumab in cardiothoracic transplant surgery. Of the 433 studies retrieved, 8 were included in the final meta-analysis., Results: In lung transplantation, alemtuzumab use was associated with lower odds of acute cellular rejection compared with antithymocyte globulin (odds ratio [OR], 0.21; 95% CI, 0.11-0.40; P < .001), lower acute rejection rates (OR, 0.12; 95% CI, 0.03-0.55; P < .01), and infection rates (OR, 0.69; 95% CI, 0.35-1.36; P = .33) when compared with basiliximab. Multivariate meta-regression analysis found that mean age, male sex, single lung transplant, double lung transplant, cytomegalovirus or Epstein-Barr virus status, idiopathic pulmonary fibrosis, cystic fibrosis, and mean ischemic time did not significantly influence acute rejection outcomes. For heart transplantation, alemtuzumab use was associated with lower acute rejection rates when compared with tacrolimus (OR, 0.44; 95% CI, 0.30-0.66; P < .001)., Conclusions: Alemtuzumab use was associated with lower rejection rates when compared with conventional induction therapy agents (antithymocyte globulin, basiliximab, and tacrolimus) in heart and lung transplantation. However, this was based on observational studies. Randomized controlled trials are needed to verify its clinical use., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: The acute cellular rejection is recognized as a factor related to the long-term viability of the heart graft. We intend to establish which factors are associated with the acute cellular rejection during the first year post heart transplant using a longitudinal model with repeated measures., Methods: A retrospective cohort study was performed with all the patients who underwent heart transplant between 2005-2018 at the Hospital Universitario San Ignacio in Bogota, Colombia. In order to determine the factors associated with the development of acute cellular rejection, a generalized estimating equation approach was used, with an interchangeable correlation structure. The lowest value of quasi-likelihood information criterion and P < .05 was considered significant., Results: Fifty-five patients (49.3 ± 11.1 years old) were included. The mortality during the first month was 16.3% and the accumulated mortality during the first year was 23.6%. The incidence of the acute cellular rejection was higher during the third month after the transplant (79.9%); most of them were acute cellular rejection grade 1. The factors associated with the development of the rejection were the cyclosporine levels out of the therapeutic range in several periods of evaluation (P < .03) and the age of the receptor (P = .049)., Conclusions: Using advanced modeling methodologies of longitudinal data we identified that the factors associated with acute cellular rejection during the first year after the transplant are related to the therapeutic levels of the calcineurin inhibitor (cyclosporin) during the first 6 months of follow-up and the age of the receptor., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Sarcopenia has recently been studied as a potential risk factor for mortality and complications after liver transplantation. We investigated the impact of low muscle mass on postoperative outcomes after living-donor liver transplantation., Methods: Our study population consisted of 100 adult recipients who underwent living-donor liver transplantation in our department between 2005 and 2017. Recipients were divided into a low-muscle-mass group (L group) and a normal-muscle-mass group (N group) based on skeletal muscle index (SMI) values, and postoperative outcomes were compared between the groups. Regarding factors that were significantly different between the groups, multivariate analyses were performed to identify predictive factors., Results: Based on the SMI definition, 47 and 53 of the recipients were categorized as having low muscle mass (L group) and normal muscle mass (N group), respectively. Comparison between the groups revealed a significantly reduced incidence of rejection (10.6% in L group vs 30.2% in N group, P = .017) and increased incidences of bacterial infection (61.7% in L group vs 37.7% in N group, P = .017) in the L group compared with the N group. The survival rate did not differ significantly between the groups. Multivariate analyses indicated that muscle mass was a significant predictive factor for both rejection and bacterial infection., Conclusion: It is important to recognize that muscle mass has an impact not only on bacterial infection but also on rejection in recipients with low muscle mass in the postoperative course of living-donor liver transplantation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: De novo complement-binding donor-specific anti-human leukocyte antigen antibodies (DSAs) are reportedly associated with an increased risk of kidney graft failure, but there is little information on preformed complement-binding DSAs. This study investigated the correlation between preformed C1q-binding DSAs and medium-term outcomes in kidney transplantation (KT)., Methods: We retrospectively studied 44 pretransplant DSA-positive patients, including 36 patients who underwent KT between April 2010 and October 2016. There were 17 patients with C1q-binding DSAs and 27 patients without C1q-binding DSAs. Clinical variables were examined in the 2 groups., Results: Patients with C1q-binding DSAs had significantly higher blood transfusion history (53.0% vs 18.6%; P = .0174), complement-dependent cytotoxicity crossmatch (CDC-XM)-positivity (29.4% vs 0%; P = .0012), and DSA median fluorescence intensity (MFI) (10,974 vs 2764; P = .0009). Among patients who were not excluded for CDC-XM-positivity and underwent KT, there was no significant difference in cumulative biopsy-proven acute rejection rate (32.5% vs 33.5%; P = .8354), cumulative graft survival, and 3-month and 12-month protocol biopsy results between patients with and without C1q-binding DSAs. Although patients with C1q-binding DSAs showed a higher incidence of delayed graft function (54.6% vs 20.0%; P = .0419), multivariate logistic regression showed that DSA MFI (P = .0124), but not C1q-binding DSAs (P = .2377), was an independent risk factor for delayed graft function., Conclusions: In patients with CDC-XM-negativity, preformed C1q-binding DSAs were not associated with incidence of antibody-mediated rejection and medium-term graft survival after KT. C1q-binding DSAs were highly correlated with DSA MFI and CDC-XM-positivity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Although living donor liver transplantation for obese recipients has increased, it has not been determined that posttransplant outcomes in obese recipients are inferior compared with nonobese recipients., Methods: From January 2001 to December 2016, there was a total of 58 (6%) obese patients (body mass index ≥30) in a cohort of 973 adult patients that underwent living donor liver transplantation. Propensity score matching and classification were performed based on the type of obesity, and there were 58 patients in the obese group and 141 patients in the nonobese group. We performed comparative analysis of posttransplant outcomes including Model for Early Allograft Function (MEAF) scoring and early allograft dysfunction (EAD)., Results: EAD was found in 11 (19%) and 31 (22%) patients in the obese and nonobese groups, respectively (P = .71). The obese group had a higher MEAF score than the nonobese group (5.2 vs 4.5, P = .007). The mean hospitalization of the obese group was shorter than in the nonobese group (32 vs 42 days, P = .003). Other posttransplant outcomes were similar between the obese and nonobese groups, including acute cellular rejection (8 vs 10 cases, P = .17), early graft failure (8 vs 12 cases, P = .30), index hospital mortality (6 vs 11 cases, P = .58), and comprehensive complication index (26.0 vs 24.6, P = .76)., Conclusion: Posttransplant outcomes of the obese group were not inferior to the nonobese group. However, obesity can impact the severity of EAD and the incidence of early graft failure, based on significantly higher MEAF scores., (Copyright © 2018. Published by Elsevier Inc.)

Objectives: This study aimed to identify the potential risk factors of acute rejection after deceased donor kidney transplantation in China., Methods: Adult kidney transplantations from deceased donors in our center from February 2004 to December 2015 were enrolled for retrospective analysis. All deceased donations complied with China's Organ Donation Program. No organs from executed prisoners were used. The incidence of clinical and biopsy-proved acute rejection was assessed with the Kaplan-Meier method, and the Cox proportional hazard model was used for multivariate analysis., Results: One-year, 2-year, 3-year and 5-year incidences of acute rejection were 12.4%, 14.2%, 14.8%, and 17.1%, respectively. Multivariate analysis demonstrated that longer pre-transplant dialysis duration (hazard ratio [HR] 1.009 per month; 95% confidence interval, 1.003-1.015; P = .003), positive pre-transplant panel reactive antibody (PRA) (positive vs negative HR 3.266; 1.570-6.793; P = .023), and increasing HLA mismatches (≥4 vs < 4 HR 2.136; 1.022-4.465; P = .044) increased the risk of acute rejection, while tacrolimus decreased acute rejection risk compared to cyclosporine (HR 0.317; 0.111-0.906; P = .032)., Conclusion: Longer pre-transplant dialysis duration, HLA mismatch, and positive pre-transplant PRA increase the risk of acute rejection, while tacrolimus helps prevent acute rejection compared to cyclosporine in deceased donor kidney transplantation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Extended-release tacrolimus (TacER), administered once daily, offers improved adherence with reduced side effects while still maintaining an immunosuppressive potency equivalent to that of conventional tacrolimus preparations., Methods: The study included 83 patients who received consecutive living-donor kidney transplants at our facility from June 2013 to December 2016. Comparisons were made between 48 cases of induction with TacER and 35 cases of induction with cyclosporine (CyA). The observation period was 3 months after transplantation. Transplanted kidney function, rejection, infectious disease, lipid abnormalities, and glucose tolerance were compared., Results: The 2 groups showed no significant difference in donor background or transplanted kidney function. Within the 3-month observation period, an acute rejection response was observed in 2 cases in the TacER group and in 8 cases in the CyA group. After transplantation, hyperlipidemia requiring medication was observed more frequently in the CyA group. The 2 groups did not show a marked difference in systemic infection or renal calcineurin inhibitor toxicity in histopathologic examination of the transplanted kidneys 3 months after surgery., Discussion: Proactive use of TacER leads to improved adherence while yielding immunosuppressive potency equivalent to that of conventional tacrolimus preparations; however, tacrolimus has a potent blood sugar-elevating effect; thus, direct comparison with the CyA group is important for assessing the side effects., Conclusion: TacER has the potential to also reduce side effects in the early stages after surgery, suggesting its potential as a drug of first choice., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The aim of this study was to determine distinctive risk factors for graft survival of living-related and deceased donor kidney transplantation (KTx)., Methods: Consecutive 536 living-related and 524 deceased donor kidney transplant recipients from February 2014 to December 2015 in a single center were enrolled for retrospective analysis. Graft survival was assessed with the Kaplan-Meier method, and the Cox proportional hazard model was used to determine independent risk factors of allograft survival., Results: One-, 3-, and 5-year graft survival rates were 98.8%, 98.5%, and 97.2%, respectively, in living-related donor KTx and were 94.9%, 91.3%, and 91.3%, respectively, in deceased donor KTx (log-rank, P < .001). Multivariate analysis demonstrated that risk factors for graft survival in living-related donor KTx were pretransplant dialysis duration (hazard ratio [HR], 1.023 per month; P = .046), delayed graft function (HR, 5.785; P = .02), and acute rejection (HR, 2.706; P = .04); risks factors in deceased donor KTx were recipient age (HR, 1.066 per year; P = .004), recipient history of diabetes mellitus (HR, 3.011; P = .03), pretransplant positive panel reactive antibody (HR, 3.353; P = .02), and donor history of hypertension (HR, 2.660; P = .046)., Conclusion: Distinctive risk factors for graft survival of living-related and deceased donor KTx were found., (Copyright © 2018. Published by Elsevier Inc.)