Frontiers in transplantation最新文献

{"title":"Cancer-related mortality among solid organ transplant recipients: systematic review and meta-analysis.","authors":"Charlotte Stephens, Rafeea Shah, Azm Hussain, Joseph Sturman, Yimeng Zhang, Felicity Baldwin, David Winter, Mike Hawkins, Raoul Reulen, Adnan Sharif","doi":"10.3389/frtra.2026.1851859","DOIUrl":"10.3389/frtra.2026.1851859","url":null,"abstract":"<p><strong>Background: </strong>Organ transplantation is associated with an increased risk of cancer-related mortality; however, estimates from international cohorts vary widely. The aim of this systematic review and meta-analysis is to quantify this risk.</p><p><strong>Methods: </strong>We searched MEDLINE and OVID Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) for population-based cohort studies reporting cancer-related mortality in adult solid organ transplant recipients up to 2nd October 2024. Meta-analysis was conducted using a restricted maximum likelihood random-effects model. Risk of bias was assessed using the Newcastle-Ottawa Scale.</p><p><strong>Results: </strong>Seventeen registry-based studies and multicentre cohort studies met inclusion criteria. The pooled standardised mortality ratio for cancer mortality was 2.21 (95% CI: 1.82-2.68). Meta-regression showed higher mortality after heart [mortality rate ratio (MRR) 2.08, 95% CI: 1.28-3.41] and lung (MRR: 1.83, 95% CI: 1.09-3.06; <i>p</i> = 0.025) transplantation compared with kidney transplantation. Geographic variation was observed, with lower mortality in East Asia.</p><p><strong>Conclusion: </strong>This meta-analysis demonstrates that solid organ transplantation is associated with an increased in overall cancer-related mortality compared with the general population, with variation by organ type and cancer site. Prostate cancer showed no excess mortality risk, supporting current guidance against additional screening. In contrast, mortality from non-Hodgkin's lymphoma was increased fivefold, consistent with the established link between immunosuppression and post-transplant lymphoproliferative disease. Notably, geographic variation was observed, with lower mortality in East Asia, likely reflecting differences lifestyle risk factors and health care structures. However significant between study heterogeneity exists, underscoring the need for tailored prevention strategies, rather than relying on aggregated global estimates in this high-risk population.</p><p><strong>Systematic review registration: </strong>https://www.crd.york.ac.uk/PROSPERO/view/CRD42024617474, identifier CRD42024617474.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1851859"},"PeriodicalIF":0.0,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13328252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148393163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Duodenal fistula secondary to erosion by an expanded polytetrafluoroethylene graft in a living donor liver transplant: a case report and review of the literature.","authors":"Kausar Makki, Nalini Kanta Ghosh, Yogesh Yadav, Tathagata Karan, Anil Agarwal, Piyush Srivastava, Vivek Vij","doi":"10.3389/frtra.2026.1799453","DOIUrl":"10.3389/frtra.2026.1799453","url":null,"abstract":"<p><p>Living donor liver transplantation (LDLT) has become an established treatment for patients with decompensated chronic liver diseases of various etiologies, acute liver failure, and liver tumors (primary and secondary). A right lobe graft without the middle hepatic vein is often preferred to achieve adequate graft weight, and an expanded polytetrafluoroethylene (ePTFE) graft is used to reconstruct the anterior sector outflow and optimize allograft function. Generally, this approach is safe and effective until optimal regeneration of the posterior sector occurs. Thrombosis of the ePTFE graft is usually inconsequential for the recipient. Other rare complications of the ePTFE graft include migration into the common bile duct, stomach, duodenum, or jejunum. We report a case of ePTFE graft migration into the duodenum, resulting in a duodenal fistula, which was resolved after endoscopic removal and clipping, in a 44-year-old patient with chronic liver disease secondary to hepatitis B and hepatitis D co-infection. The uniqueness of this case lies in the rarity of this complication and its successful endoscopic management. At 6 months of follow-up, the patient is doing well, with normal allograft function and complete healing of the duodenal fistula. This case highlights the potential complication of an inert ePTFE graft in LDLT, which requires clinical suspicion, evaluation, and can be managed endoscopically.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1799453"},"PeriodicalIF":0.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Echocardiography-guided assessment of mouse cardiac transplant rejection improves model reproducibility.","authors":"Angela Clemens, Sara Alibrandi, Paolo Molinari, Johan Noble, Barbara Franchin, Miguel Fribourg, Paolo Cravedi, Nicholas Chun","doi":"10.3389/frtra.2026.1840060","DOIUrl":"10.3389/frtra.2026.1840060","url":null,"abstract":"<p><strong>Background: </strong>The mouse heterotopic heart transplant model is a widely used system for dissecting mechanisms of graft rejection and identifying new therapeutic targets, owing to its relative technical simplicity and the availability of well-defined inbred strains. One limitation of the model is that monitoring of the non-life sustaining implanted graft by manual palpation does not provide information regarding the magnitude of the anti-donor immune response and is operator-dependent. Building on previous studies suggesting that trans-abdominal ultrasonography can detect graft rejection more precisely than manual palpation, we tested if changes in motion mode (M-mode) ultrasound also correlated with the magnitude of the anti-donor T cell response.</p><p><strong>Methods: </strong>We performed sets of MHC-mismatched heterotopic heart transplants in mice and quantified the accuracy of palpation vs. ultrasonography in determining graft rejection. In an additional set of mice, we performed mixed lymphocyte reactions to quantify anti-donor T cell immunity at a fixed time point (usual experimental design) or at time points determined by changes in allograft M-mode analysis.</p><p><strong>Conclusions: </strong>The data demonstrate that ultrasonography is superior to manual palpation for determining graft rejection and newly shows that changes in M-mode associate with the magnitude of anti-donor T cell immunity. These findings are important to increase reproducibility and translational impact of studies using this model.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1840060"},"PeriodicalIF":0.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13318921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical presentation, management, and outcomes of post-transplant lymphoproliferative disorder in renal and pancreas transplantation: a 22-year experience.","authors":"Kian Emami, Jane Norman, Titus Augustine","doi":"10.3389/frtra.2026.1830197","DOIUrl":"10.3389/frtra.2026.1830197","url":null,"abstract":"<p><strong>Background: </strong>Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of solid organ transplantation associated with long-term immunosuppression and Epstein-Barr virus (EBV) reactivation. This study analyses the clinical presentation, diagnostic pathways, therapeutic strategies and outcomes of PTLD in renal and pancreatic transplant recipients at the Manchester Centre for Transplantation.</p><p><strong>Methods: </strong>A retrospective cohort study was carried out on a cohort of 73 patients diagnosed with PTLD between 2002 and 2025 following renal, simultaneous pancreas-kidney (SPK) or pancreas-only transplantation. Data were collected from electronic medical records and analysed descriptively. Clinical presentations were categorised into organ system involvement. Time from presentation to diagnosis and survival outcomes were assessed.</p><p><strong>Results: </strong>The median time from transplant to PTLD diagnosis was 132 months, with 56% of cases diagnosed more than 10 years post-transplant. Monomorphic PTLD, in particular diffuse large B-cell lymphoma (DLBCL), was the most common subtype. EBV-positivity was seen in all early cases and in 57% overall. Abdominal and B symptoms were the most frequent presentations. Bleeding and/or anaemia were significantly associated with diagnostic delay (<i>p</i> = 0.045), and delays over one month were associated with reduced survival (<i>p</i> = 0.061). Complete or partial remission was achieved in 75% of patients. The 5-year overall survival rate was 68% while 1-year survival was 83% and death-censored graft survival was 82%.</p><p><strong>Conclusion: </strong>In our cohort, PTLD in transplant recipients presents with diverse symptoms and can occur several years post-transplant highlighting the need for long-term vigilance. Streamlined referral pathways and increased awareness could reduce diagnostic delays. Establishing a national PTLD registry would benefit future research.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1830197"},"PeriodicalIF":0.0,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13319058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148371735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An exploration of markers of microvascular dysfunction in kidney transplant recipients randomized to belatacept: no clinical impact of CNIs on endothelial function.","authors":"Edwin O W Bredewold, Rudmer J Postma, Joe Chan, My H S Svensson, Annette Bruchfeld, Johannes W de Fijter, Hans Furuland, Anders Hartmann, Lars Mjornstedt, Karin Skov, Inga Soveri, Soeren S Sorensen, Bengt Fellstrom, Jacques M Duijs, Roel Bijkerk, Joris I Rotmans, Anton-Jan van Zonneveld","doi":"10.3389/frtra.2026.1812847","DOIUrl":"10.3389/frtra.2026.1812847","url":null,"abstract":"<p><strong>Introduction: </strong>Side effects of calcineurin inhibitors (CNI) comprise hypertension, diabetes and nephrotoxicity, and endothelial dysfunction (ED) has often been implicated. Belatacept, a co-stimulation blocker, may offer a more favourable vascular profile.</p><p><strong>Methods: </strong>We investigated markers of endothelial function in blood samples from kidney transplant recipients (KTR) that were converted from CNI to belatacept. We assessed established markers of ED including soluble thrombomodulin, P-selectin and angiopoietin 1 and 2. In addition, we assessed expression levels of microRNAs (miRNAs), which have been identified as discriminative markers for ED, rejection and renal fibrosis in the setting of transplantation. Lastly, we used patient samples and CNI-dilution series in a validated model of ED in which changes in morphological characteristics of endothelial cells were evaluated.</p><p><strong>Results: </strong>Unexpectedly, we found no differences in our assays between both groups. We did observe dose-related effects of CNI on endothelial cell (EC) morphology upon direct exposure of EC to tacrolimus and ciclosporin A, but a similar effect was not seen when plasma samples of KTR who were converted to belatacept were compared with samples from KTR on CNI's.</p><p><strong>Discussion: </strong>These data suggest that CNI-side-effects bundled under the term \"CNI-toxicity\" are not derived from a significant clinical effect of CNI on endothelial function.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1812847"},"PeriodicalIF":0.0,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13294043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148348481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From prediction to practice: artificial intelligence as an enabling layer in liver transplant care - reflections on ILTS 2025.","authors":"Ali Zarrinpar, Avery F Orinion","doi":"10.3389/frtra.2026.1879684","DOIUrl":"10.3389/frtra.2026.1879684","url":null,"abstract":"<p><p>Liver transplantation has become increasingly complex and data-intensive, demanding rapid, high-stakes clinical decisions as patient and organ conditions evolve. The surge of multidimensional clinical datasets has sparked strong interest in artificial intelligence (AI) and machine-learning (ML) as decision-support tools. The 2025 International Liver Transplantation Society (ILTS) annual meeting in Singapore highlighted that AI is now permeating every facet of liver transplantation, from donor-recipient matching and intra-operative navigation to post-transplant pharmacologic management. Early-stage models have shown impressive predictive performance in risk stratification for rejection, infection, and postoperative complications, as well as in individualized immunosuppression dosing and AI-assisted imaging/histopathology. However, real-world implementation has exposed persistent obstacles: data silos, limited generalizability, suboptimal explainability, and workflow friction that can erode clinician trust. Poor integration into existing clinical workflows may also increase cognitive burden for clinicians and reduce adoption of otherwise promising tools. This perspective synthesizes the ILTS 2025 messages and recent transplant literature, proposing a pragmatic three-stage roadmap for AI adoption over the next five years. The roadmap moves from near-term, well-validated decision-support alerts integrated into electronic health records, through mid-term hybrid human-AI teams that embed explainable AI (XAI) into clinical workflows, to long-term global AI consortia that foster federated learning and equitable model deployment. Central to this vision is a shift from \"AI as an autonomous decision-maker\" to \"augmented intelligence that amplifies human expertise while remaining transparent and equitable,\" ensuring that AI serves as an enabling layer that augments, rather than replaces, clinical judgment.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1879684"},"PeriodicalIF":0.0,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreatic tissue engineering: towards a vascularized bioengineered cure for diabetes.","authors":"Ji Ho Park, Khadijat A Olawuyi, Neekita R Jikaria, Jazzmyn S Dawes, Ishak E Dabsha, André A Dick, Dino J Ravnic","doi":"10.3389/frtra.2026.1768497","DOIUrl":"10.3389/frtra.2026.1768497","url":null,"abstract":"<p><p>Type 1 diabetes results from autoimmune destruction of pancreatic β-cells, and while whole-organ pancreas and islet transplantation can restore endogenous insulin secretion, both are limited by donor scarcity, early inflammatory injury, hypoxia, and the need for lifelong immunosuppression. Pancreatic tissue engineering has therefore emerged as a strategy to generate scalable, transplantable constructs capable of reestablishing physiological glucose regulation. However, as native islets depend on a robust microvascular network for oxygen delivery, nutrients and coordinated hormone secretion, insufficient vascularization remains the dominant cause of engineered graft failure. This review provides an overview of (a) the current state of pancreas transplant, (b) strategies for vascularized and immunoprotective pancreatic constructs, (c) cell differentiation strategies beyond of pancreatic β-cells, (d) translational progress in animal and human clinical trials, (e) key challenges in clinical translation, (f) ethical and regulatory considerations, and (g) future directions for tissue engineered pancreatic constructs. Our goal is to provide the reader with a translational overview that spans biology, tissue engineering, and clinical translation.</p><p><strong>Impact statement: </strong>This translational review provides a concise review of tissue engineering efforts to date within the context of engineered pancreatic constructs. Our paper systematically and logically discusses current developments, challenges, and novel approaches in pancreatic tissue engineering. It provides a digestible starting point for understanding the various approaches and the implications of successful tissue engineering strategies that can be used to develop transplantable pancreatic constructs.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1768497"},"PeriodicalIF":0.0,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13284089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148311270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycan-encoded immune checkpoints and allorecognition: a mechanistic framework for transplantation and organ engineering.","authors":"Md Mohosin Rana, Stephen G Withers, Jonathan C Choy, Jayachandran N Kizhakkedathu","doi":"10.3389/frtra.2026.1841203","DOIUrl":"10.3389/frtra.2026.1841203","url":null,"abstract":"<p><p>Glycans constitute a structurally diverse and immunologically instructive layer that shapes how transplanted tissues are interpreted by the host immune system. Although glycoengineering approaches and glycocalyx-focused strategies have gained momentum, the mechanistic pathways through which immune cells decode glycan information remain underexplored in transplantation biology. This hybrid Perspective integrates selected mechanistic foundations with a broader conceptual framework that positions glycans as upstream immune checkpoints governing graft recognition and early innate-adaptive integration. We synthesize advances across four major axes of glycan-regulated immunity: Siglec (Sialic acid-binding immunoglobulin-type lectin)-mediated inhibitory circuits that calibrate macrophage, neutrophil, and NK-cell activation; C-type lectin receptor pathways that program antigen-presenting cells and govern antigen routing; NK-cell glycan-sensing mechanisms shaped by sialylation density, glycan topology, and ischemia-reperfusion-induced glycocalyx collapse; and complement regulation through Factor H, which interprets sialic acid motifs to restrain alternative pathway amplification. We further examine how these innate pathways intersect with glycan-dependent modulation of direct, indirect, and semi-direct allorecognition, including effects on MHC stability, exosomal transfer, antigen uptake, and T-cell intrinsic glycan checkpoints. Together, these mechanisms reveal that glycans function as a pre-recognition code that precedes and conditions classical protein-centric checkpoints by initiating, amplifying and sustaining the classical pathways, and influencing whether grafts are classified as self-like, stressed, or foreign. By consolidating these pathways into a unified model, this Perspective highlights glycan composition and architecture as a foundational design parameter for next-generation immune-compatible organ modifications and outlines mechanistic priorities for advancing glycan-informed strategies in transplantation.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1841203"},"PeriodicalIF":0.0,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148298611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hepatic adenomatosis leading to liver failure and symptomatic extrinsic cardiac compression treated with liver transplantation: a case report and literature review.","authors":"Antoine Robert, Nicole Bhave, Jared Christensen, Kyle Sheetz, Nicole Tomm, Robert John Fontana","doi":"10.3389/frtra.2026.1810971","DOIUrl":"10.3389/frtra.2026.1810971","url":null,"abstract":"<p><p>We report an unusual case of a 34-year-old woman with liver and right heart failure caused by mass effect from a large hepatic adenoma compressing the bile duct, right atrium, and vena cava that was successfully managed with sequential radioembolization and orthotopic liver transplantation. This case highlights the potential complications of large adenomas and associated downsizing strategies needed to achieve a successful outcome. We believe that this is a topic of interest to the journal readership as hepatic adenomatosis is a rare indication for liver transplantation that many readers may not be familiar with.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1810971"},"PeriodicalIF":0.0,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13272425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Benchmarking the urinary transplant metabolome of kidney transplant recipients using healthy organ donors.","authors":"Naser B N Shehab, Kim C M Lammers-Jannink, Margriet H Riphagen, Siawosh K Eskandari, Jamil R Azzi, Martin H de Borst, Kerstin Bunte, Stephan J L Bakker, M Rebecca Heiner-Fokkema","doi":"10.3389/frtra.2026.1833811","DOIUrl":"10.3389/frtra.2026.1833811","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplantation is the only curative treatment for end-stage kidney disease, providing markedly improved outcomes over dialysis. In search of optimized long-term outcomes, recent studies have demonstrated alterations in the metabolic state of kidney transplant recipients (KTRs) may contribute to chronic graft outcomes. Here, we sought to benchmark metabolic perturbations associated with the post-transplant state using a set of extensively characterized kidney transplant donors as healthy control.</p><p><strong>Methods: </strong>In this cross-sectional, single-center study, we used untargeted GC-MS to profile the 24 h urine from 121 stable KTRs (0.2-38.9 yrs post-transplant) and 94 extensively screened healthy potential kidney donors (HC) from the TransplantLines Biobank and Cohort Study. We assessed group differences using linear models adjusted for baseline covariates including eGFR, and the multivariable OPLS-DA model for global separation. ROC analysis was performed on the top discriminants. GlobalTest Pathway enrichment was used to map differentially abundant metabolites in metabolic pathways from the KEGG database.</p><p><strong>Results: </strong>In KTRs, 28 metabolites were significantly altered compared to HC; 13 of which were elevated and 15 decreased in KTRs. Among them, methylmalonic acid (AUROC 0.886), citric acid (AUROC 0.870), and glycolic acid (AUROC 0.804) were all reduced in KTRs and showed the strongest in-sample separation between the groups. OPLS-DA achieved good group separation (R²Y = 0.733, Q² = 0.621) with no signs of overfitting. Twenty pathways were significantly perturbed, led by the TCA cycle, glyoxylate and dicarboxylate metabolism and branched-chain amino acid degradation. Sensitivity analyses examining alternative normalizations, excluding patients with diabetes or proteinuria, adjusting for statin use, and stratifying by eGFR and transplant vintage, were highly concordant with the main analysis (Spearman <i>ρ</i> > 0.87 for all pairwise comparisons).</p><p><strong>Conclusion: </strong>Urinary metabolic profiles in KTRs are consistent with alterations in TCA cycle, glyoxylate and dicarboxylate metabolism, and branched chain amino acid degradation after transplantation. Although causality cannot be established from this cross-sectional design, these findings may reflect altered energy metabolism in the post-transplant state.</p>","PeriodicalId":519976,"journal":{"name":"Frontiers in transplantation","volume":"5 ","pages":"1833811"},"PeriodicalIF":0.0,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13272301/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}