Pub Date : 2026-01-01Epub Date: 2025-11-02DOI: 10.1016/j.trre.2025.100970
Kristen D. Belfield , Krysta Walter , Jennifer E. Marvin , Ryan W. Bonner , Rebecca B. Carlson , Kristen R. Szempruch
Introduction
Current methods of estimating glomerular filtration rate (eGFR) are commonly based on serum creatinine (SCr); however, cystatin C (CysC)-based methods have recently become more available with increased uptake of CysC testing. Currently, there is a gap in literature reviewing the use of CysC in non-kidney transplant recipients. The aim of this literature review is to evaluate the use of CysC in the assessment of GFR in non-kidney transplant recipients.
Methods
Electronic databases Embase, PubMed, Cumulative Index for Nursing and Allied Health Literature, ClinicalTrials.gov, and EU Clinical Trials Register were searched.
Results
Of the 487 unique citations, 11 were included (eight liver, two lung, and one heart transplant). Five liver transplant studies found a better prognostic parameter or correlation to measured GFR with CysC based equations, and two liver and two lung transplant studies found the combined Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRSCr-CysC equation demonstrated higher correlation, accuracy, or performance than with either SCr or CysC-based equations.
Conclusion
The inclusion of CysC-based eGFR measurements, in particular the 2012 and 2021 CKD-EPI eGFRSCr-CysC equation, for GFR assessment overall correlated with the control assessments more than its comparators in non-kidney transplant recipients while maintaining accuracy.
目前估计肾小球滤过率(eGFR)的方法通常基于血清肌酐(SCr);然而,基于胱抑素C (CysC)的方法最近随着CysC检测的增加而变得更加可行。目前,关于CysC在非肾移植受者中的应用的文献综述存在空白。本文献综述的目的是评估CysC在评估非肾移植受者GFR中的应用。方法检索Embase、PubMed、Nursing and Allied Health Literature Cumulative Index、ClinicalTrials.gov和EU ClinicalTrials Register等电子数据库。结果487例文献引用中,有11例文献被引用(8例肝移植,2例肺移植,1例心脏移植)。五项肝移植研究发现基于CysC的方程与测量的GFR有更好的预后参数或相关性,两项肝和两项肺移植研究发现慢性肾脏疾病流行病学合作(CKD-EPI)联合egfrcr -CysC方程比基于SCr或CysC的方程具有更高的相关性、准确性或性能。结论纳入基于cysc的eGFR测量,特别是2012年和2021年CKD-EPI egfrcr - cysc方程,用于GFR评估总体上与非肾移植受者对照评估的相关性大于其比较物,同时保持准确性。
{"title":"Use of cystatin C as a marker for estimated glomerular filtration rate in non-kidney transplant recipients","authors":"Kristen D. Belfield , Krysta Walter , Jennifer E. Marvin , Ryan W. Bonner , Rebecca B. Carlson , Kristen R. Szempruch","doi":"10.1016/j.trre.2025.100970","DOIUrl":"10.1016/j.trre.2025.100970","url":null,"abstract":"<div><h3>Introduction</h3><div>Current methods of estimating glomerular filtration rate (eGFR) are commonly based on serum creatinine (SCr); however, cystatin C (CysC)-based methods have recently become more available with increased uptake of CysC testing. Currently, there is a gap in literature reviewing the use of CysC in non-kidney transplant recipients. The aim of this literature review is to evaluate the use of CysC in the assessment of GFR in non-kidney transplant recipients.</div></div><div><h3>Methods</h3><div>Electronic databases Embase, PubMed, Cumulative Index for Nursing and Allied Health Literature, <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, and EU Clinical Trials Register were searched.</div></div><div><h3>Results</h3><div>Of the 487 unique citations, 11 were included (eight liver, two lung, and one heart transplant). Five liver transplant studies found a better prognostic parameter or correlation to measured GFR with CysC based equations, and two liver and two lung transplant studies found the combined Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR<sub>SCr-CysC</sub> equation demonstrated higher correlation, accuracy, or performance than with either SCr or CysC-based equations.</div></div><div><h3>Conclusion</h3><div>The inclusion of CysC-based eGFR measurements, in particular the 2012 and 2021 CKD-EPI eGFR<sub>SCr-CysC</sub> equation, for GFR assessment overall correlated with the control assessments more than its comparators in non-kidney transplant recipients while maintaining accuracy.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100970"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145520974","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}
Pub Date : 2026-01-01Epub Date: 2025-12-04DOI: 10.1016/j.trre.2025.100982
Pedro Fragoso , Andreia Borges , Francisco Caramelo , Helena Oliveira Sá , Arnaldo Figueiredo , Rui Alves , Rita Leal
Background
Kidney transplant recipients with graft failure face reduced access to retransplantation due to sensitization. Evidence-based guidance on optimal immunosuppression (IS) management after graft loss is limited. This systematic review with meta-analysis assessed the impact of rapid versus prolonged IS withdrawal on sensitization and safety outcomes.
Methods
Cohort studies comparing IS withdrawal strategies after graft failure were systematically reviewed. Outcomes included HLA sensitization, graft nephrectomy, hospitalization, and mortality. Searches were conducted in Medline, Embase, and the Cochrane Library. Pooled odds ratios (ORs) and weighted mean differences (WMD) were calculated using a random-effects model.
Results
Thirteen studies comprising 1531 patients were included. Prolonging immunosuppression (>3 months of at least two immunosuppressants) was associated with significantly lower odds of graft exclusion (OR 0.41; 95 % CI 0.27–0.64), and a trend toward reduced donor-specific antibody formation and cPRA stabilization, although not statistically significant. Sensitivity analysis confirmed an association between early IS withdrawal and higher cPRA at follow-up (WMD +0.30, 0.01–0.59). The IS withdrawal strategy did not impact hospitalization, mortality, or retransplantation.
Conclusion
Prolonging IS after kidney graft failure reduces nephrectomy risk and favours a decrease in HLA sensitization, without added morbidity and mortality. Further prospective studies are warranted to provide stronger evidence-based data.
背景:肾移植失败的受者由于致敏性降低了再移植的机会。基于证据的移植物丢失后最佳免疫抑制(IS)管理指导是有限的。本系统综述和荟萃分析评估了快速和长期停药对致敏性和安全性结果的影响。方法:系统回顾比较移植失败后IS退出策略的队列研究。结果包括HLA致敏、移植肾切除术、住院和死亡率。在Medline、Embase和Cochrane图书馆进行了检索。采用随机效应模型计算合并优势比(ORs)和加权平均差(WMD)。结果:纳入13项研究,1531例患者。延长免疫抑制(至少使用两种免疫抑制剂3个月)与移植物排斥几率显著降低相关(OR 0.41; 95% CI 0.27-0.64),并有减少供体特异性抗体形成和cPRA稳定的趋势,尽管没有统计学意义。敏感性分析证实早期IS戒断与随访时较高的cPRA之间存在关联(WMD +0.30, 0.01-0.59)。IS退出策略不影响住院、死亡率或再移植。结论:肾移植失败后延长IS可降低肾切除术风险,有利于降低HLA敏化,未增加发病率和死亡率。进一步的前瞻性研究有必要提供更有力的循证数据。
{"title":"The impact of immunosuppression withdrawal strategies on sensitization and safety outcomes after kidney transplant failure: A systematic review with meta-analysis","authors":"Pedro Fragoso , Andreia Borges , Francisco Caramelo , Helena Oliveira Sá , Arnaldo Figueiredo , Rui Alves , Rita Leal","doi":"10.1016/j.trre.2025.100982","DOIUrl":"10.1016/j.trre.2025.100982","url":null,"abstract":"<div><h3>Background</h3><div>Kidney transplant recipients with graft failure face reduced access to retransplantation due to sensitization. Evidence-based guidance on optimal immunosuppression (IS) management after graft loss is limited. This systematic review with meta-analysis assessed the impact of rapid versus prolonged IS withdrawal on sensitization and safety outcomes.</div></div><div><h3>Methods</h3><div>Cohort studies comparing IS withdrawal strategies after graft failure were systematically reviewed. Outcomes included HLA sensitization, graft nephrectomy, hospitalization, and mortality. Searches were conducted in Medline, Embase, and the Cochrane Library. Pooled odds ratios (ORs) and weighted mean differences (WMD) were calculated using a random-effects model.</div></div><div><h3>Results</h3><div>Thirteen studies comprising 1531 patients were included. Prolonging immunosuppression (>3 months of at least two immunosuppressants) was associated with significantly lower odds of graft exclusion (OR 0.41; 95 % CI 0.27–0.64), and a trend toward reduced donor-specific antibody formation and cPRA stabilization, although not statistically significant. Sensitivity analysis confirmed an association between early IS withdrawal and higher cPRA at follow-up (WMD +0.30, 0.01–0.59). The IS withdrawal strategy did not impact hospitalization, mortality, or retransplantation.</div></div><div><h3>Conclusion</h3><div>Prolonging IS after kidney graft failure reduces nephrectomy risk and favours a decrease in HLA sensitization, without added morbidity and mortality. Further prospective studies are warranted to provide stronger evidence-based data.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100982"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717243","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}
Pub Date : 2026-01-01Epub Date: 2025-12-12DOI: 10.1016/j.trre.2025.100984
Wellgner Fernandes Oliveira Amador , Isabelle Castro Vitor , Milena Ramos Tomé , Igor Boechat Silveira , Marina de Assis Bezerra Cavalcanti Leite , Pedro Robson Costa Passos , Valbert Oliveira Costa Filho , Mariana Macambira Noronha , Yohanna Idsabella Rossi , Rodrigo Vieira Motta , Guilherme Grossi Lopes Cançado
Autoimmune hepatitis (AIH) recurrence after liver transplantation (LT) compromises graft function and outcomes. Evidence on risk factors is heterogeneous. We assessed recurrence rates and patient-, immunological-, clinical-, and donor-related predictors. A systematic review and meta-analysis of observational studies of LT recipients with AIH was conducted. PubMed, Embase, and CENTRAL were searched. Outcomes were recurrence incidence and associated risk factors. Random-effects models were fitted in R, with pooled proportions, odds ratios (ORs), and mean differences (MDs). Thirty-nine studies (n = 2600) met inclusion criteria. The pooled recurrence proportion was 21 % (95 %CI, 18 to 25 %). Recurrence was more frequent in children than adults (31 % vs 21 %; p-interaction = 0.03). Younger age was associated with recurrence (MD, −6.60 years; 95 %CI, −11.43 to −1.76). Acute rejection (OR, 1.92; 95 %CI, 1.11 to 3.31) and chronic rejection (OR, 2.64; 95 %CI, 0.99 to 6.99) were significant predictors. No significant associations were observed for sex, MELD score, AIH subtype, HLA-DR3/DR4 status, primary calcineurin inhibitor (tacrolimus vs cyclosporine), or donor type. Overall, one in five LT recipients with AIH experience recurrence, with a higher burden in pediatric and younger patients. Younger age and prior acute or chronic rejection confer the greatest risk. Targeted monitoring and tailored immunosuppression may help mitigate recurrence.
{"title":"Global epidemiology and determinants of autoimmune hepatitis recurrence post- liver transplantation: A systematic review and meta-analysis","authors":"Wellgner Fernandes Oliveira Amador , Isabelle Castro Vitor , Milena Ramos Tomé , Igor Boechat Silveira , Marina de Assis Bezerra Cavalcanti Leite , Pedro Robson Costa Passos , Valbert Oliveira Costa Filho , Mariana Macambira Noronha , Yohanna Idsabella Rossi , Rodrigo Vieira Motta , Guilherme Grossi Lopes Cançado","doi":"10.1016/j.trre.2025.100984","DOIUrl":"10.1016/j.trre.2025.100984","url":null,"abstract":"<div><div>Autoimmune hepatitis (AIH) recurrence after liver transplantation (LT) compromises graft function and outcomes. Evidence on risk factors is heterogeneous. We assessed recurrence rates and patient-, immunological-, clinical-, and donor-related predictors. A systematic review and meta-analysis of observational studies of LT recipients with AIH was conducted. PubMed, Embase, and CENTRAL were searched. Outcomes were recurrence incidence and associated risk factors. Random-effects models were fitted in R, with pooled proportions, odds ratios (ORs), and mean differences (MDs). Thirty-nine studies (<em>n</em> = 2600) met inclusion criteria. The pooled recurrence proportion was 21 % (95 %CI, 18 to 25 %). Recurrence was more frequent in children than adults (31 % vs 21 %; p-interaction = 0.03). Younger age was associated with recurrence (MD, −6.60 years; 95 %CI, −11.43 to −1.76). Acute rejection (OR, 1.92; 95 %CI, 1.11 to 3.31) and chronic rejection (OR, 2.64; 95 %CI, 0.99 to 6.99) were significant predictors. No significant associations were observed for sex, MELD score, AIH subtype, HLA-DR3/DR4 status, primary calcineurin inhibitor (tacrolimus vs cyclosporine), or donor type. Overall, one in five LT recipients with AIH experience recurrence, with a higher burden in pediatric and younger patients. Younger age and prior acute or chronic rejection confer the greatest risk. Targeted monitoring and tailored immunosuppression may help mitigate recurrence.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100984"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770280","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}
Ischemia-reperfusion injury (IRI) critically affects graft survival following organ transplantation, where complement activation mediates the inflammation, endothelial damage, and adaptive immune responses. This review synthesizes the mechanisms through which the classical, lectin, and alternative complement pathways drive organ-specific IRI pathophysiology by generating anaphylatoxins (C3a/C5a) and membrane attack complexes (C5b-9). Specifically, locally synthesized C3 predominates in renal tubular injury, hepatic C3a/C5a paradoxically promote regeneration while exacerbating inflammation, cardiac C4d/C3d deposits correlate with rejection, and lectin pathway activation (notably via mannose-binding lectin, MBL) underlies primary graft dysfunction (PGD) in lung transplantation. Advances in therapeutic research highlight the values of complement inhibitors, including anti-C5 agents (e.g., eculizumab) that mitigate delayed graft function (DGF) in kidney transplantation, C1 esterase inhibitors that attenuate IRI and antibody-mediated rejection (AMR), C5a receptor antagonists (e.g., PMX53) that extend graft survival in preclinical models, and soluble complement receptor 1 (sCR1) that alleviates multi-organ IRI. Future research should focus on optimizing organ-specific targeting strategies, validating the long-term efficacy and safety of these agents via clinical trials, and exploring synergistic immunomodulatory approaches to further improve transplantation outcomes.
{"title":"Research progress on the complement system in ischemia-reperfusion injury of organ transplantation","authors":"Cheng Zhang , Kun Dong , Junze Chen , Guanmiao Chen , Chunqiang Dong","doi":"10.1016/j.trre.2025.100981","DOIUrl":"10.1016/j.trre.2025.100981","url":null,"abstract":"<div><div>Ischemia-reperfusion injury (IRI) critically affects graft survival following organ transplantation, where complement activation mediates the inflammation, endothelial damage, and adaptive immune responses. This review synthesizes the mechanisms through which the classical, lectin, and alternative complement pathways drive organ-specific IRI pathophysiology by generating anaphylatoxins (C3a/C5a) and membrane attack complexes (C5b-9). Specifically, locally synthesized C3 predominates in renal tubular injury, hepatic C3a/C5a paradoxically promote regeneration while exacerbating inflammation, cardiac C4d/C3d deposits correlate with rejection, and lectin pathway activation (notably via mannose-binding lectin, MBL) underlies primary graft dysfunction (PGD) in lung transplantation. Advances in therapeutic research highlight the values of complement inhibitors, including anti-C5 agents (e.g., eculizumab) that mitigate delayed graft function (DGF) in kidney transplantation, C1 esterase inhibitors that attenuate IRI and antibody-mediated rejection (AMR), C5a receptor antagonists (e.g., PMX53) that extend graft survival in preclinical models, and soluble complement receptor 1 (sCR1) that alleviates multi-organ IRI. Future research should focus on optimizing organ-specific targeting strategies, validating the long-term efficacy and safety of these agents via clinical trials, and exploring synergistic immunomodulatory approaches to further improve transplantation outcomes.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100981"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770294","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}
Pub Date : 2026-01-01Epub Date: 2025-12-17DOI: 10.1016/j.trre.2025.100988
Maggie Cheng , Steven Cao Tri Huynh , Reid Dale , Maria Elizabeth Currie
Current multi-organ candidates are prioritized primarily based on single-organ risk scores. Once the primary organ is allocated, the secondary organ follows to the same recipient, resulting in waitlisted single-organ candidates being skipped in allocation.
Our previous work examined the ethical and statistical alignment of single-organ risk scores. Here, we aim to extend our analysis to multi-organ transplantation policies in the United States, surveying the current state of multi-organ candidate prioritization and the challenges of conducting high-quality research in multi-organ transplantation.
We systematically searched PubMed for published literature on the allocation of all multi-organ pairs involving the liver, kidney, lungs, and heart. After screening based on our inclusion and exclusion criteria, we identified 126 articles to include in this review. These include 31 articles for Heart-Lung, 24 for Heart-Kidney, 52 for Liver-Kidney, and 19 for Liver-Heart transplantation. We did not discuss the remaining organ pairs due to insufficient literature to provide a balanced analysis.
Provider-, center-, and region-dependent variations exist in multi-organ practices due to evolving national guidelines and a lack of standardized institutional protocols for candidate evaluation and listing. The use of single-organ risk scores in multi-organ allocation has not been statistically validated, therefore raising concerns about applicability.
Multi-organ transplant research relies heavily on single-center reports, case studies, and registry-based analyses. The frequent re-use of national registry data limits the novelty and reliability of multi-organ research. We encourage future efforts to consider exploratory, prospective, and perhaps randomized-controlled trials to advance understanding and strengthen the evidence base in multi-organ transplantation.
{"title":"History and challenges of multi-organ allocation in the United States: A systematic review","authors":"Maggie Cheng , Steven Cao Tri Huynh , Reid Dale , Maria Elizabeth Currie","doi":"10.1016/j.trre.2025.100988","DOIUrl":"10.1016/j.trre.2025.100988","url":null,"abstract":"<div><div>Current multi-organ candidates are prioritized primarily based on single-organ risk scores. Once the primary organ is allocated, the secondary organ follows to the same recipient, resulting in waitlisted single-organ candidates being skipped in allocation.</div><div>Our previous work examined the ethical and statistical alignment of single-organ risk scores. Here, we aim to extend our analysis to multi-organ transplantation policies in the United States, surveying the current state of multi-organ candidate prioritization and the challenges of conducting high-quality research in multi-organ transplantation.</div><div>We systematically searched PubMed for published literature on the allocation of all multi-organ pairs involving the liver, kidney, lungs, and heart. After screening based on our inclusion and exclusion criteria, we identified 126 articles to include in this review. These include 31 articles for Heart-Lung, 24 for Heart-Kidney, 52 for Liver-Kidney, and 19 for Liver-Heart transplantation. We did not discuss the remaining organ pairs due to insufficient literature to provide a balanced analysis.</div><div>Provider-, center-, and region-dependent variations exist in multi-organ practices due to evolving national guidelines and a lack of standardized institutional protocols for candidate evaluation and listing. The use of single-organ risk scores in multi-organ allocation has not been statistically validated, therefore raising concerns about applicability.</div><div>Multi-organ transplant research relies heavily on single-center reports, case studies, and registry-based analyses. The frequent re-use of national registry data limits the novelty and reliability of multi-organ research. We encourage future efforts to consider exploratory, prospective, and perhaps randomized-controlled trials to advance understanding and strengthen the evidence base in multi-organ transplantation.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100988"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822564","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}
Pub Date : 2026-01-01Epub Date: 2025-11-03DOI: 10.1016/j.trre.2025.100971
Michael Corr , Nawal Khan , Dessi Malinova , Alexander P. Maxwell , Gareth J. McKay , Matthew D. Griffin
Kidney transplantation provides the best survival advantage for children, adolescents, and young adults with end-stage kidney disease, yet this group paradoxically experiences the poorest long-term graft survival. Immune-mediated rejection is the predominant cause, but the cellular mechanisms that underpin this age-related disparity remain incompletely defined. This review synthesises current evidence on the impact of immune ageing across adaptive and innate compartments, focusing on T cells, B cells, and natural killer (NK) cells. In younger recipients, a large naïve T- and B-cell pool, robust thymic output, and efficient germinal centre activity confer heightened alloimmune reactivity, driving increased risk of acute cellular and antibody-mediated rejection. In contrast, older recipients exhibit features of immunosenescence, including loss of CD28 expression, accumulation of terminally differentiated effector subsets, impaired germinal centre responses, and attenuated NK cytotoxicity, resulting in diminished capacity to mount de novo responses but greater vulnerability to infection. These immune trajectories have direct clinical implications: younger recipients may require intensified, mechanism-targeted immunosuppression, whereas older recipients may be more amenable to minimisation or tolerance protocols. We further highlight emerging evidence for premature immunosenescence in paediatric dialysis populations, the contribution of age-associated B cells and NK subsets, and the role of immunophenotype-guided therapeutic strategies. Current uniform immunosuppression protocols inadequately account for developmental and age-related immune heterogeneity. We argue for an age- and immune phenotype–informed approach to therapy, integrating longitudinal immune profiling, biomarker development, and systems immunology to improve risk stratification, promote tolerance, and ultimately extend allograft survival across all age groups.
{"title":"Immune cell subsets in young kidney transplant recipients: Mechanistic and clinical perspectives","authors":"Michael Corr , Nawal Khan , Dessi Malinova , Alexander P. Maxwell , Gareth J. McKay , Matthew D. Griffin","doi":"10.1016/j.trre.2025.100971","DOIUrl":"10.1016/j.trre.2025.100971","url":null,"abstract":"<div><div>Kidney transplantation provides the best survival advantage for children, adolescents, and young adults with end-stage kidney disease, yet this group paradoxically experiences the poorest long-term graft survival. Immune-mediated rejection is the predominant cause, but the cellular mechanisms that underpin this age-related disparity remain incompletely defined. This review synthesises current evidence on the impact of immune ageing across adaptive and innate compartments, focusing on T cells, B cells, and natural killer (NK) cells. In younger recipients, a large naïve T- and B-cell pool, robust thymic output, and efficient germinal centre activity confer heightened alloimmune reactivity, driving increased risk of acute cellular and antibody-mediated rejection. In contrast, older recipients exhibit features of immunosenescence, including loss of CD28 expression, accumulation of terminally differentiated effector subsets, impaired germinal centre responses, and attenuated NK cytotoxicity, resulting in diminished capacity to mount de novo responses but greater vulnerability to infection. These immune trajectories have direct clinical implications: younger recipients may require intensified, mechanism-targeted immunosuppression, whereas older recipients may be more amenable to minimisation or tolerance protocols. We further highlight emerging evidence for premature immunosenescence in paediatric dialysis populations, the contribution of age-associated B cells and NK subsets, and the role of immunophenotype-guided therapeutic strategies. Current uniform immunosuppression protocols inadequately account for developmental and age-related immune heterogeneity. We argue for an age- and immune phenotype–informed approach to therapy, integrating longitudinal immune profiling, biomarker development, and systems immunology to improve risk stratification, promote tolerance, and ultimately extend allograft survival across all age groups.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100971"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145442533","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}
Pub Date : 2026-01-01Epub Date: 2025-12-15DOI: 10.1016/j.trre.2025.100986
Zhi-Cheng Gao , Hui Wan , Guan-Yue Shan , Yu-Xin Zhang , Zi-Jun Sun , Yun-Peng Shi , Hai-Jun Li
Natural killer (NK) cells are crucial components of the innate immune system and are abundantly present in the liver, a unique immune organ frequently subjected to clinical transplantation. NK cells regulate their functional state through a finely tuned balance between activating and inhibitory receptors, allowing them to eliminate target cells independently of major histocompatibility complex class I (MHC-I) restriction. In the context of liver transplantation, NK cells respond dynamically to ischemia-reperfusion injury, donor-recipient immune mismatch and immunosuppressive treatments, thereby influencing graft acceptance, rejection and infection control. Activated NK cells release a broad range of cytokines and chemokines, shaping both innate and adaptive immune responses. This review highlights the multifaceted roles of NK cells in transplant immunity, emphasizes their clinical and translational significance, and summarizes emerging therapeutic strategies that target NK cells. Collectively, it provides insights into NK cell biology and underscores their potential in improving long-term outcomes after liver transplantation.
{"title":"The role of natural killer cells in the immune response after liver transplantation","authors":"Zhi-Cheng Gao , Hui Wan , Guan-Yue Shan , Yu-Xin Zhang , Zi-Jun Sun , Yun-Peng Shi , Hai-Jun Li","doi":"10.1016/j.trre.2025.100986","DOIUrl":"10.1016/j.trre.2025.100986","url":null,"abstract":"<div><div>Natural killer (NK) cells are crucial components of the innate immune system and are abundantly present in the liver, a unique immune organ frequently subjected to clinical transplantation. NK cells regulate their functional state through a finely tuned balance between activating and inhibitory receptors, allowing them to eliminate target cells independently of major histocompatibility complex class I (MHC-I) restriction. In the context of liver transplantation, NK cells respond dynamically to ischemia-reperfusion injury, donor-recipient immune mismatch and immunosuppressive treatments, thereby influencing graft acceptance, rejection and infection control. Activated NK cells release a broad range of cytokines and chemokines, shaping both innate and adaptive immune responses. This review highlights the multifaceted roles of NK cells in transplant immunity, emphasizes their clinical and translational significance, and summarizes emerging therapeutic strategies that target NK cells. Collectively, it provides insights into NK cell biology and underscores their potential in improving long-term outcomes after liver transplantation.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100986"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145776946","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}
Pub Date : 2026-01-01Epub Date: 2025-12-19DOI: 10.1016/j.trre.2025.100985
Animesh Singla , Shirley Cai , Ahmer Hameed , Henry Pleass , Tess Cooper , Melanie Wyld , Angela C. Webster
Introduction
Balancing bleeding risk with graft thrombosis is a challenge in transplantation surgery. This systematic review assessed the efficacy and safety of intraoperative administration of intravenous (IV) unfractionated heparin (UFH) bolus during adult kidney transplantation.
Methodology
We searched MEDLINE, Embase, and CENTRAL (from inception to May 2025) for comparative studies of any design recruiting adults undergoing living or deceased donor kidney transplantation (PROSPERO CRD42023391473), that examined intraoperative IV UFH as a perioperative intervention. Study quality was assessed using the Newcastle Ottawa Scale. Outcomes: Graft thrombosis (including subgroup analysis of arterial thromboses), bleeding complications, delayed graft function, and transplant nephrectomy. Relative and absolute effects were synthesised using a random-effects model as risk ratio (RR) with 95 % confidence intervals (CI). Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.
Results
Three retrospective cohort studies (1989 participants) met inclusion criteria. Study quality was rated as ‘fair’ in two studies and ‘good’ in one study. There was no difference for graft thrombosis with intraoperative IV UFH (3 studies, 1989 participants, RR 1.02, 95 % CI 0.49–2.12, I2 = 0 %, very low certainty evidence). Sub-group analysis also did not identify any difference for arterial thrombosis risk. Nearly all graft thromboses (17/23) resulted in transplant nephrectomy. IV UFH did not increase bleeding complications (3 studies, 1989 participants, RR 1.29, 95 % CI 0.78–2.13, I2 68 %, very low certainty evidence). There was no difference in delayed graft function (2 studies, 461 participants, RR = 0.95, 95 % CI 0.57 to 1.58, I2 = 40 %, very low certainty evidence).
Conclusion
Despite its common use in clinical practice, evidence supporting intraoperative IV UFH during kidney transplant surgery is sparce and of very low certainty. Current evidence does not demonstrate a reduction in graft thrombosis or delayed graft function demonstrated with intraoperative IV UFH, nor a clear increase in bleeding complications. High-quality prospective studies are needed to clarify the net clinical benefit of intraoperative UFH in kidney transplant surgery.
在移植手术中平衡出血风险和移植物血栓形成是一个挑战。本系统综述评估了成人肾移植术中静脉注射未分割肝素(UFH)丸的有效性和安全性。方法:我们检索MEDLINE, Embase和CENTRAL(从成立到2025年5月),以比较任何设计招募接受活体或已故供体肾移植的成人(PROSPERO CRD42023391473)的研究,这些研究检查术中IV UFH作为围手术期干预。研究质量采用纽卡斯尔渥太华量表进行评估。结果:移植物血栓形成(包括动脉血栓亚组分析),出血并发症,移植物功能延迟,移植肾切除术。相对效应和绝对效应采用随机效应模型作为风险比(RR),置信区间为95%。证据的确定性采用GRADE(建议评估、发展和评价分级)方法进行评估。结果:三个回顾性队列研究(1989名参与者)符合纳入标准。研究质量在两项研究中被评为“一般”,在一项研究中被评为“良好”。术中静脉注射UFH在移植物血栓形成方面没有差异(3项研究,1989名参与者,RR 1.02, 95% CI 0.49-2.12, I2 = 0%,非常低确定性证据)。亚组分析也没有发现动脉血栓形成风险的任何差异。几乎所有的移植物血栓形成(17/23)导致移植肾切除术。IV UFH不增加出血并发症(3项研究,1989名受试者,RR 1.29, 95% CI 0.78-2.13, I2 68%,极低确定性证据)。延迟移植物功能没有差异(2项研究,461名参与者,RR = 0.95, 95% CI 0.57至1.58,I2 = 40%,非常低确定性证据)。结论:尽管在临床实践中普遍使用,但支持肾移植手术术中静脉注射UFH的证据很少,而且确定性很低。目前的证据并没有表明术中静脉UFH能减少移植物血栓形成或延迟移植物功能,也没有明显增加出血并发症。需要高质量的前瞻性研究来阐明术中UFH在肾移植手术中的净临床效益。
{"title":"Intraoperative unfractionated heparin (UFH) for kidney transplantation: A systematic review and meta-analysis","authors":"Animesh Singla , Shirley Cai , Ahmer Hameed , Henry Pleass , Tess Cooper , Melanie Wyld , Angela C. Webster","doi":"10.1016/j.trre.2025.100985","DOIUrl":"10.1016/j.trre.2025.100985","url":null,"abstract":"<div><h3>Introduction</h3><div>Balancing bleeding risk with graft thrombosis is a challenge in transplantation surgery. This systematic review assessed the efficacy and safety of intraoperative administration of intravenous (IV) unfractionated heparin (UFH) bolus during adult kidney transplantation.</div></div><div><h3>Methodology</h3><div>We searched MEDLINE, Embase, and CENTRAL (from inception to May 2025) for comparative studies of any design recruiting adults undergoing living or deceased donor kidney transplantation (PROSPERO CRD42023391473), that examined intraoperative IV UFH as a perioperative intervention. Study quality was assessed using the Newcastle Ottawa Scale. Outcomes: Graft thrombosis (including subgroup analysis of arterial thromboses), bleeding complications, delayed graft function, and transplant nephrectomy. Relative and absolute effects were synthesised using a random-effects model as risk ratio (RR) with 95 % confidence intervals (CI). Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach.</div></div><div><h3>Results</h3><div>Three retrospective cohort studies (1989 participants) met inclusion criteria. Study quality was rated as ‘fair’ in two studies and ‘good’ in one study. There was no difference for graft thrombosis with intraoperative IV UFH (3 studies, 1989 participants, RR 1.02, 95 % CI 0.49–2.12, I<sup>2</sup> = 0 %, very low certainty evidence). Sub-group analysis also did not identify any difference for arterial thrombosis risk. Nearly all graft thromboses (17/23) resulted in transplant nephrectomy. IV UFH did not increase bleeding complications (3 studies, 1989 participants, RR 1.29, 95 % CI 0.78–2.13, I<sup>2</sup> 68 %, very low certainty evidence). There was no difference in delayed graft function (2 studies, 461 participants, RR = 0.95, 95 % CI 0.57 to 1.58, I<sup>2</sup> = 40 %, very low certainty evidence).</div></div><div><h3>Conclusion</h3><div>Despite its common use in clinical practice, evidence supporting intraoperative IV UFH during kidney transplant surgery is sparce and of very low certainty. Current evidence does not demonstrate a reduction in graft thrombosis or delayed graft function demonstrated with intraoperative IV UFH, nor a clear increase in bleeding complications. High-quality prospective studies are needed to clarify the net clinical benefit of intraoperative UFH in kidney transplant surgery.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100985"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806976","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}
Late-onset Pneumocystis jirovecii pneumonia (PCP) is increasingly recognized in kidney transplant recipients (KTRs) despite widespread prophylaxis. However, its prevalence and risk factors remain unclear.
Methods
We systematically searched electronic databases for studies published up to May 1, 2025, that reported prevalence or risk factors of late-onset PCP. Pooled prevalence, weighted mean differences (WMDs), and pooled odds ratios (ORs) were synthesized using a random-effects model.
Results
Of 1448 studies screened, 24 met inclusion criteria, comprising 57,662 KTRs, of whom 556 developed late-onset PCP. The pooled prevalence was 1.28 % (95 %CI 0.90–1.65). Lymphocyte counts were significantly lower in the infection group (WMD –408.34 cells/μL; 95 %CI –706.03 to −110.66). Risk was significantly increased with ABO-incompatible transplantation (OR 4.12; 95 %CI 1.04–16.30), rituximab induction (OR 4.77; 95 %CI, 1.50–15.21), corticosteroid (OR 2.56; 95 %CI 1.00–6.52) or mammalian target of rapamycin inhibitor (mTORi) maintenance (OR 2.37; 95 %CI 1.27–4.42), CMV infection (OR 5.21; 95 %CI 2.45–11.10), and rejection episodes (OR 2.93; 95 %CI 1.72–4.99), particularly when treated with plasma exchange, intravenous methylprednisolone, or rituximab. In contrast, cotrimoxazole prophylaxis reduced risk (OR 0.06; 95 %CI 0.01–0.60). Late-onset PCP was associated with graft loss (OR 6.11; 95 %CI 2.98–12.55) and mortality (OR 10.48; 95 %CI 1.92–57.16).
Conclusions
Although uncommon, late-onset PCP in KTRs is strongly linked with ABO-incompatible transplantation, lack of cotrimoxazole prophylaxis, lymphopenia, CMV infection, corticosteroid and mTORi, and rejection. KTRs with these high-risk features, including those receiving mTORi and corticosteroid maintenance, should be considered for prolonged or life-long PCP prophylaxis.
背景:迟发性肺囊虫肺炎(PCP)越来越多地在肾移植受者(KTRs)中得到认可,尽管广泛的预防。然而,其流行程度和危险因素仍不清楚。方法:我们系统地检索了电子数据库中截至2025年5月1日发表的关于迟发性PCP患病率或危险因素的研究。合并患病率、加权平均差异(wmd)和合并优势比(ORs)采用随机效应模型进行综合。结果:在筛选的1448项研究中,24项符合纳入标准,包括57,662例ktr,其中556例发展为晚发性PCP。合并患病率为1.28% (95% CI 0.90-1.65)。感染组淋巴细胞计数明显降低(WMD为-408.34 cells/μL; 95% CI为-706.03 ~ -110.66)。abo血型不相容移植(OR 4.12; 95% CI 1.04-16.30)、利妥昔单抗诱导(OR 4.77; 95% CI 1.50-15.21)、皮质类固醇(OR 2.56; 95% CI 1.00-6.52)或哺乳动物雷帕霉素靶抑制剂(mTORi)维持(OR 2.37; 95% CI 1.27-4.42)、巨细胞病毒感染(OR 5.21; 95% CI 2.45-11.10)和排斥事件(OR 2.93; 95% CI 1.72-4.99),尤其是当接受血浆交换、静脉注射甲基泼尼松龙或利妥昔单抗治疗时,风险显著增加。相反,复方新诺明预防可降低风险(OR 0.06; 95% CI 0.01-0.60)。晚发性PCP与移植物丢失(OR 6.11; 95% CI 2.98-12.55)和死亡率(OR 10.48; 95% CI 1.92-57.16)相关。结论:虽然不常见,但KTRs的晚发性PCP与abo血型不相容移植、缺乏复方新诺明预防、淋巴细胞减少、巨细胞病毒感染、皮质类固醇和mTORi以及排斥反应密切相关。具有这些高风险特征的ktr患者,包括那些接受mTORi和皮质类固醇维持治疗的患者,应考虑长期或终身预防PCP。
{"title":"Late-onset pneumocystis pneumonia after kidney transplantation: A systematic review and meta-analysis of prevalence, risk factors, and outcomes","authors":"Sirihatai Konwai , Chanyanuch Rakpithayanon , Thunyatorn Wuttiputhanun , Asada Leelahavanichkul , Natavudh Townamchai , Jakapat Vanichanan , Kamonwan Jutivorakool , Yingyos Avihingsanon , Kearkiat Praditpornsilpa , Suwasin Udomkarnjananun","doi":"10.1016/j.trre.2025.100972","DOIUrl":"10.1016/j.trre.2025.100972","url":null,"abstract":"<div><h3>Background</h3><div>Late-onset <em>Pneumocystis jirovecii</em> pneumonia (PCP) is increasingly recognized in kidney transplant recipients (KTRs) despite widespread prophylaxis. However, its prevalence and risk factors remain unclear.</div></div><div><h3>Methods</h3><div>We systematically searched electronic databases for studies published up to May 1, 2025, that reported prevalence or risk factors of late-onset PCP. Pooled prevalence, weighted mean differences (WMDs), and pooled odds ratios (ORs) were synthesized using a random-effects model.</div></div><div><h3>Results</h3><div>Of 1448 studies screened, 24 met inclusion criteria, comprising 57,662 KTRs, of whom 556 developed late-onset PCP. The pooled prevalence was 1.28 % (95 %CI 0.90–1.65). Lymphocyte counts were significantly lower in the infection group (WMD –408.34 cells/μL; 95 %CI –706.03 to −110.66). Risk was significantly increased with ABO-incompatible transplantation (OR 4.12; 95 %CI 1.04–16.30), rituximab induction (OR 4.77; 95 %CI, 1.50–15.21), corticosteroid (OR 2.56; 95 %CI 1.00–6.52) or mammalian target of rapamycin inhibitor (mTORi) maintenance (OR 2.37; 95 %CI 1.27–4.42), CMV infection (OR 5.21; 95 %CI 2.45–11.10), and rejection episodes (OR 2.93; 95 %CI 1.72–4.99), particularly when treated with plasma exchange, intravenous methylprednisolone, or rituximab. In contrast, cotrimoxazole prophylaxis reduced risk (OR 0.06; 95 %CI 0.01–0.60). Late-onset PCP was associated with graft loss (OR 6.11; 95 %CI 2.98–12.55) and mortality (OR 10.48; 95 %CI 1.92–57.16).</div></div><div><h3>Conclusions</h3><div>Although uncommon, late-onset PCP in KTRs is strongly linked with ABO-incompatible transplantation, lack of cotrimoxazole prophylaxis, lymphopenia, CMV infection, corticosteroid and mTORi, and rejection. KTRs with these high-risk features, including those receiving mTORi and corticosteroid maintenance, should be considered for prolonged or life-long PCP prophylaxis.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"40 1","pages":"Article 100972"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145491378","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}