Transplantation最新文献

{"title":"Taurine Deficiency Is a Hallmark of Injured Kidney Allografts.","authors":"Anna Rinaldi, Pietro E Cippà, Ivan Nemazanyy, Dany Anglicheau, Nicolas Pallet","doi":"10.1097/TP.0000000000004987","DOIUrl":"https://doi.org/10.1097/TP.0000000000004987","url":null,"abstract":"<p><strong>Background: </strong>Taurine is one of the most abundant amino acids in humans. Low taurine levels are associated with cellular senescence, mitochondrial dysfunction, DNA damage, and inflammation in mouse, all of which can be reversed by supplementation. It is unknown whether taurine metabolism is associated with kidney allograft function and survival.</p><p><strong>Methods: </strong>We performed urine metabolomic profiling of kidney transplant recipients in the early and late phases after transplantation combined with transcriptomic analysis of human kidney allografts. Single-nucleus RNA sequencing data sets of mouse kidneys after ischemia-reperfusion injury were analyzed. We analyzed the association of urinary taurine levels and taurine metabolism genes with kidney function, histology, and graft survival.</p><p><strong>Results: </strong>Urine taurine concentrations were significantly lower in kidney transplant recipients who experienced delayed graft function. In a mouse model of ischemia-reperfusion injury, the taurine biosynthesis gene, CSAD , but not the taurine transporter SLC6A6 , was repressed. In the late stage of transplantation, low level of taurine in urine was associated with impaired kidney function and chronic structural changes. Urine taurine level in the lowest tertile was predictive of graft loss. Expression of the taurine transporter SLC6A6 in the upper median, but not CSAD , was associated with chronic kidney injury and was predictive of graft loss.</p><p><strong>Conclusions: </strong>Low urine taurine level is a marker of injury in the kidney allograft, is associated with poor kidney function, is associated with chronic histological changes, and is predictive of graft survival. The differential expression of CSAD and SLC6A6 , depending on the time after transplantation and marks of injury, highlights different mechanisms affecting taurine metabolism.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward a Fair Adjusted Analysis of Kidney Graft Survival.","authors":"Auxiliadora Mazuecos, Marta Crespo, Emilio Rodrigo, Eva Gavela, Alex Gutiérrez-Dalmau, Domingo Hernández, María O López, Edoardo Melilli, María O Valentín, Sofía Zárraga, Beatriz Domínguez-Gil","doi":"10.1097/TP.0000000000005088","DOIUrl":"https://doi.org/10.1097/TP.0000000000005088","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor-derived Cell-free DNA-Ready for Prime Time Yet?","authors":"Stephan Ensminger, Luciano Potena","doi":"10.1097/TP.0000000000005151","DOIUrl":"10.1097/TP.0000000000005151","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potentiating Renal Regeneration Using Mesenchymal Stem Cells: Erratum.","authors":"","doi":"10.1097/TP.0000000000005150","DOIUrl":"https://doi.org/10.1097/TP.0000000000005150","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacomicrobiomics: Immunosuppressive Drugs and Microbiome Interactions in Transplantation.","authors":"Moataz E Mohamed, Abdelrahman Saqr, Christopher Staley, Guillaume Onyeaghala, Levi Teigen, Casey R Dorr, Rory P Remmel, Weihua Guan, William S Oetting, Arthur J Matas, Ajay K Israni, Pamala A Jacobson","doi":"10.1097/TP.0000000000004926","DOIUrl":"10.1097/TP.0000000000004926","url":null,"abstract":"<p><p>The human microbiome is associated with human health and disease. Exogenous compounds, including pharmaceutical products, are also known to be affected by the microbiome, and this discovery has led to the field of pharmacomicobiomics. The microbiome can also alter drug pharmacokinetics and pharmacodynamics, possibly resulting in side effects, toxicities, and unanticipated disease response. Microbiome-mediated effects are referred to as drug-microbiome interactions (DMI). Rapid advances in the field of pharmacomicrobiomics have been driven by the availability of efficient bacterial genome sequencing methods and new computational and bioinformatics tools. The success of fecal microbiota transplantation for recurrent Clostridioides difficile has fueled enthusiasm and research in the field. This review focuses on the pharmacomicrobiome in transplantation. Alterations in the microbiome in transplant recipients are well documented, largely because of prophylactic antibiotic use, and the potential for DMI is high. There is evidence that the gut microbiome may alter the pharmacokinetic disposition of tacrolimus and result in microbiome-specific tacrolimus metabolites. The gut microbiome also impacts the enterohepatic recirculation of mycophenolate, resulting in substantial changes in pharmacokinetic disposition and systemic exposure. The mechanisms of these DMI and the specific bacteria or communities of bacteria are under investigation. There are little or no human DMI data for cyclosporine A, corticosteroids, and sirolimus. The available evidence in transplantation is limited and driven by small studies of heterogeneous designs. Larger clinical studies are needed, but the potential for future clinical application of the pharmacomicrobiome in avoiding poor outcomes is high.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold Ischemia Time and Delayed Graft Function in Kidney Transplantation: A Paired Kidney Analysis.","authors":"Syed Ali Husain, Sohil Khanna, Miko Yu, Joel T Adler, David C Cron, Kristen L King, Jesse D Schold, Sumit Mohan","doi":"10.1097/TP.0000000000005006","DOIUrl":"10.1097/TP.0000000000005006","url":null,"abstract":"<p><strong>Background: </strong>We aimed to understand the association between cold ischemia time (CIT) and delayed graft function (DGF) after kidney transplantation and the impact of organ pumping on that association.</p><p><strong>Methods: </strong>Retrospective cohort study using US registry data. We identified kidney pairs from the same donor where both kidneys were transplanted but had a CIT difference >0 and ≤20 h. We determined the frequency of concordant (both kidneys with/without DGF) or discordant (only 1 kidney DGF) DGF outcomes. Among discordant pairs, we computed unadjusted and adjusted relative risk of DGF associated with longer-CIT status, when then repeated this analysis restricted to pairs where only the longer-CIT kidney was pumped.</p><p><strong>Results: </strong>Among 25 831 kidney pairs included, 71% had concordant DGF outcomes, 16% had only the longer-CIT kidney with DGF, and 13% had only the shorter-CIT kidney with DGF. Among discordant pairs, longer-CIT status was associated with a higher risk of DGF in unadjusted and adjusted models. Among pairs where only the longer-CIT kidney was pumped, longer-CIT kidneys that were pumped had a lower risk of DGF than their contralateral shorter-CIT kidneys that were not pumped regardless of the size of the CIT difference.</p><p><strong>Conclusions: </strong>Most kidney pairs have concordant DGF outcomes regardless of CIT difference, but even small increases in CIT raise the risk of DGF. Organ pumping may mitigate and even overcome the adverse consequences of prolonged CIT on the risk of DGF, but prospective studies are needed to better understand this relationship.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11338744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrocardiography-based Artificial Intelligence Algorithms Aid in Prediction of Long-term Mortality After Kidney Transplantation.","authors":"Niv Pencovich, Byron H Smith, Zachi I Attia, Francisco Lopez Jimenez, Andrew J Bentall, Carrie A Schinstock, Hasan A Khamash, Caroline C Jadlowiec, Tambi Jarmi, Shennen A Mao, Walter D Park, Tayyab S Diwan, Paul A Friedman, Mark D Stegall","doi":"10.1097/TP.0000000000005023","DOIUrl":"10.1097/TP.0000000000005023","url":null,"abstract":"<p><strong>Background: </strong>Predicting long-term mortality postkidney transplantation (KT) using baseline clinical data presents significant challenges. This study aims to evaluate the predictive power of artificial intelligence (AI)-enabled analysis of preoperative electrocardiograms (ECGs) in forecasting long-term mortality following KT.</p><p><strong>Methods: </strong>We analyzed preoperative ECGs from KT recipients at three Mayo Clinic sites (Minnesota, Florida, and Arizona) between January 1, 2006, and July 30, 2021. The study involved 6 validated AI algorithms, each trained to predict future development of atrial fibrillation, aortic stenosis, low ejection fraction, hypertrophic cardiomyopathy, amyloid heart disease, and biological age. These algorithms' outputs based on a single preoperative ECG were correlated with patient mortality data.</p><p><strong>Results: </strong>Among 6504 KT recipients included in the study, 1764 (27.1%) died within a median follow-up of 5.7 y (interquartile range: 3.00-9.29 y). All AI-ECG algorithms were independently associated with long-term all-cause mortality ( P < 0.001). Notably, few patients had a clinical cardiac diagnosis at the time of transplant, indicating that AI-ECG scores were predictive even in asymptomatic patients. When adjusted for multiple clinical factors such as recipient age, diabetes, and pretransplant dialysis, AI algorithms for atrial fibrillation and aortic stenosis remained independently associated with long-term mortality. These algorithms also improved the C-statistic for predicting overall (C = 0.74) and cardiac-related deaths (C = 0.751).</p><p><strong>Conclusions: </strong>The findings suggest that AI-enabled preoperative ECG analysis can be a valuable tool in predicting long-term mortality following KT and could aid in identifying patients who may benefit from enhanced cardiac monitoring because of increased risk.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comments on: The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation.","authors":"Phuong-Thu T Pham, Phuong-Chi T Pham","doi":"10.1097/TP.0000000000005087","DOIUrl":"10.1097/TP.0000000000005087","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11335075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of Newer Nucleos(t)ide Analogs After Hepatitis B Immunoglobulin Discontinuation Against Hepatitis B and D Recurrence in Liver Transplant Recipients.","authors":"Evangelos Cholongitas, Theodora Oikonomou, Konstantina Bafa, Emmanouil Sinakos, George V Papatheodoridis, Ioannis Goulis","doi":"10.1097/TP.0000000000005027","DOIUrl":"10.1097/TP.0000000000005027","url":null,"abstract":"<p><strong>Background: </strong>The use of nucleos(t)ide analogs (NAs) with a high genetic barrier to resistance, namely entecavir and tenofovir, has improved the efficacy of antiviral prophylaxis against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, the optimal duration and dosage of hepatitis B immunoglobulin (HBIG) administration, particularly in patients transplanted for HBV and hepatitis D virus (HDV) coinfection, remains controversial.</p><p><strong>Methods: </strong>We evaluated 28 patients transplanted for HBV/HDV cirrhosis. After LT, each patient received a fixed scheme of low-dose HBIG plus NA for 6 mo post-LT and then continued with long-term NA prophylaxis (entecavir: 8, tenofovir: 20 patients).</p><p><strong>Results: </strong>During 72 mo of follow-up, reappearance of hepatitis B surface antigen at low titers was observed in 1 (3.6%) patient at 33 mo after HBIG discontinuation, which became negative after a single dose of HBIG 1000 IU/L, whereas both serum HBV DNA and HDV RNA remained persistently undetectable and without any clinical or biochemical evidence of HBV/HDV recurrence.</p><p><strong>Conclusions: </strong>We showed for the first time the efficacy of a short, fixed scheme of low-dose HBIG plus NA followed by long-term NA monoprophylaxis against HBV/HDV recurrence after LT, although careful follow-up is needed after HBIG discontinuation, whereas further larger studies are needed to confirm these findings.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of Maximum Tolerable Cold Ischemia Time in a Mouse Model of Cervical Heterotopic Uterus Transplantation.","authors":"Xin Luo, Shengnan Yu, Bing Liu, Qisheng Zheng, Xin Zhou, Ke An, Jiaying Zhong, Licheng Wu, Helong Dai, Zhongquan Qi, Junjie Xia","doi":"10.1097/TP.0000000000004979","DOIUrl":"10.1097/TP.0000000000004979","url":null,"abstract":"<p><strong>Background: </strong>Uterus transplantation (UTx) is an emerging treatment for uterine factor infertility. Determining the maximum tolerable cold ischemia time is crucial for successful UTx. However, the limit for cold ischemia in the uterus is unclear. This study aimed to examine cold ischemia's effects on mouse uteri and identify the maximum cold ischemia duration that uteri can endure.</p><p><strong>Methods: </strong>We systematically assessed the tolerance of mouse uteri to extended cold ischemia, 24 h, 36 h, and 48 h, using the cervical heterotopic UTx model. Multiple indicators were used to evaluate ischemia-reperfusion injury, including reperfusion duration, macroscopic examination, oxidative stress, inflammation, and histopathology. The function of transplants was evaluated through estrous cycle monitoring and embryo transfer.</p><p><strong>Results: </strong>Mouse uteri subjected to 48 h of cold ischemia exhibited significant delays and insufficiencies in reperfusion, substantial tissue necrosis, and loss of the estrous cycle. Conversely, uteri that underwent cold ischemia within 36 h showed long survival, regular estrous cycles, and fertility.</p><p><strong>Conclusions: </strong>Our study demonstrated that mouse uteri can endure at least 36 h of cold ischemia, extending the known limits for cold ischemia and providing a pivotal reference for research on the prevention and treatment of cold ischemic injury in UTx.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140159128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}