Everolimus (EVL) is an effective post-transplant immunosuppressant; however, its optimal trough concentration when switching from calcineurin inhibitors (CNIs) remains unknown. The optimal dosing troughs for CNI-to-EVL switching in kidney transplant recipients were investigated. We searched multiple electronic databases (from inception to March 15, 2024) to identify double-blind or open-label randomized controlled trials evaluating groups (all ages, both sexes) that converted from CNIs to EVL and continued CNI treatment in kidney transplant recipients. Treatment responses, defined as changes in estimated glomerular filtration rate (eGFR), mortality, dropouts for any reason, and adverse events, were the outcomes. We performed a random-effects, one-stage dose–effect meta-analysis with restricted cubic splines. Nine studies were included, comprising 1872 participants. Changes in eGFR increased with increasing trough concentrations; however, the evidence was highly uncertain (95 % effective dose: 4.13 ng/mL, odds ratio [OR]: 1.31, 95 % confidence interval [CI]: 0.10–9.50). Mortality was not estimated owing to the low number of events. The evidence for the relationship between EVL trough levels and treatment discontinuation was also highly uncertain (OR: 1.31, 95 % CI: 0.10–9.39). Adverse events increased with a switch to EVL; however, this evidence was also uncertain (OR: 1.31, 95 % CI: 0.10–9.60). This study could not indicate an appropriate optimal EVL trough concentration owing to the high result uncertainty, and the results do not support the routine switch from CNIs to EVL. Further trials are required to explore the CNI-to-EVL switch timing and the effects of increased EVL dosing to establish a more definitive therapeutic strategy.
{"title":"Effect of everolimus administration on renal function in renal transplant recipients: A systematic review and dose–response meta-analysis","authors":"Takehiro Ohyama , Shodai Yoshihiro , Tomoyuki Fujikura , Takamasa Miyauchi , Yuki Kataoka","doi":"10.1016/j.trre.2025.100911","DOIUrl":"10.1016/j.trre.2025.100911","url":null,"abstract":"<div><div>Everolimus (EVL) is an effective post-transplant immunosuppressant; however, its optimal trough concentration when switching from calcineurin inhibitors (CNIs) remains unknown. The optimal dosing troughs for CNI-to-EVL switching in kidney transplant recipients were investigated. We searched multiple electronic databases (from inception to March 15, 2024) to identify double-blind or open-label randomized controlled trials evaluating groups (all ages, both sexes) that converted from CNIs to EVL and continued CNI treatment in kidney transplant recipients. Treatment responses, defined as changes in estimated glomerular filtration rate (eGFR), mortality, dropouts for any reason, and adverse events, were the outcomes. We performed a random-effects, one-stage dose–effect meta-analysis with restricted cubic splines. Nine studies were included, comprising 1872 participants. Changes in eGFR increased with increasing trough concentrations; however, the evidence was highly uncertain (95 % effective dose: 4.13 ng/mL, odds ratio [OR]: 1.31, 95 % confidence interval [CI]: 0.10–9.50). Mortality was not estimated owing to the low number of events. The evidence for the relationship between EVL trough levels and treatment discontinuation was also highly uncertain (OR: 1.31, 95 % CI: 0.10–9.39). Adverse events increased with a switch to EVL; however, this evidence was also uncertain (OR: 1.31, 95 % CI: 0.10–9.60). This study could not indicate an appropriate optimal EVL trough concentration owing to the high result uncertainty, and the results do not support the routine switch from CNIs to EVL. Further trials are required to explore the CNI-to-EVL switch timing and the effects of increased EVL dosing to establish a more definitive therapeutic strategy.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100911"},"PeriodicalIF":3.6,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454604","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}
Pub Date : 2025-02-16DOI: 10.1016/j.trre.2025.100912
Bader A. Alfares , Martijn V. Verhagen , Rudi A.J.O. Dierckx , Hubert P. van der Doef , Robbert J. de Haas , Reinoud P.H. Bokkers
Portal vein stenosis (PVS) is a relatively frequent vascular complication after pediatric liver transplantation (pLT) that may result in portal hypertension. The aim of this study was to provide an overview of various diagnostic methods and imaging criteria used to diagnose PVS and to report their diagnostic accuracy. Until August 2024, PubMed and Embase were searched for English-language manuscripts with >5 patients and radiologic features of PVS. Three investigators screened articles and extracted data. The risk of bias was assessed using QUADAS-2. Twenty studies were identified. Doppler ultrasound (DUS) was the most used imaging method, followed by computed tomography (CT) and digital subtraction angiography (DSA). In studies comparing DUS with other diagnostic modalities, an elevated peak systolic velocity (PSV) and velocity ratio (VR) emerged as reliable indicators of PVS. An anastomotic diameter of <3.5 mm showed the best diagnostic performance, with a sensitivity of 100 % and a specificity of 91.8 %. Although DUS is the preferred initial diagnostic tool due to its non-invasive nature, CT and DSA remain essential in cases where DUS findings are inconclusive or when more detailed vascular assessment is necessary. DSA also allows for simultaneous endovascular treatment, further enhancing its utility. This systematic review emphasizes the need for larger, prospective studies to directly compare the diagnostic performance of these imaging modalities and to establish more consistent and reliable criteria for diagnosing PVS after pLT.
门静脉狭窄(PVS)是小儿肝移植(pLT)后比较常见的血管并发症,可能导致门静脉高压。本研究旨在概述用于诊断 PVS 的各种诊断方法和成像标准,并报告其诊断准确性。在2024年8月之前,我们在PubMed和Embase上检索了有>5名患者和PVS放射学特征的英文稿件。三名研究人员筛选了文章并提取了数据。采用QUADAS-2评估偏倚风险。共确定了 20 项研究。多普勒超声(DUS)是最常用的成像方法,其次是计算机断层扫描(CT)和数字减影血管造影(DSA)。在比较 DUS 与其他诊断方法的研究中,峰值收缩速度(PSV)和速度比值(VR)升高成为 PVS 的可靠指标。吻合口直径为 3.5 毫米的诊断效果最佳,敏感性为 100%,特异性为 91.8%。尽管 DUS 因其非侵入性而成为首选的初步诊断工具,但在 DUS 结果不确定或需要进行更详细的血管评估时,CT 和 DSA 仍然是必不可少的。DSA 还可同时进行血管内治疗,进一步提高了其实用性。本系统综述强调有必要进行更大规模的前瞻性研究,以直接比较这些成像模式的诊断性能,并为 pLT 后 PVS 的诊断建立更一致、更可靠的标准。
{"title":"Diagnosing portal vein stenosis after pediatric liver transplantation: A systematic review","authors":"Bader A. Alfares , Martijn V. Verhagen , Rudi A.J.O. Dierckx , Hubert P. van der Doef , Robbert J. de Haas , Reinoud P.H. Bokkers","doi":"10.1016/j.trre.2025.100912","DOIUrl":"10.1016/j.trre.2025.100912","url":null,"abstract":"<div><div>Portal vein stenosis (PVS) is a relatively frequent vascular complication after pediatric liver transplantation (pLT) that may result in portal hypertension. The aim of this study was to provide an overview of various diagnostic methods and imaging criteria used to diagnose PVS and to report their diagnostic accuracy. Until August 2024, PubMed and Embase were searched for English-language manuscripts with >5 patients and radiologic features of PVS. Three investigators screened articles and extracted data. The risk of bias was assessed using QUADAS-2. Twenty studies were identified. Doppler ultrasound (DUS) was the most used imaging method, followed by computed tomography (CT) and digital subtraction angiography (DSA). In studies comparing DUS with other diagnostic modalities, an elevated peak systolic velocity (PSV) and velocity ratio (VR) emerged as reliable indicators of PVS. An anastomotic diameter of <3.5 mm showed the best diagnostic performance, with a sensitivity of 100 % and a specificity of 91.8 %. Although DUS is the preferred initial diagnostic tool due to its non-invasive nature, CT and DSA remain essential in cases where DUS findings are inconclusive or when more detailed vascular assessment is necessary. DSA also allows for simultaneous endovascular treatment, further enhancing its utility. This systematic review emphasizes the need for larger, prospective studies to directly compare the diagnostic performance of these imaging modalities and to establish more consistent and reliable criteria for diagnosing PVS after pLT.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100912"},"PeriodicalIF":3.6,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143437656","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}
Pub Date : 2025-01-22DOI: 10.1016/j.trre.2025.100910
Gayathri Giri , Daniel Doherty , Shazli Azmi , Hussein Khambalia , Giuseppe Giuffrida , Zia Moinuddin , David van Dellen
Background
Pancreas Transplantation (PT) provides optimal treatment for patients with severe complicated Type 1 Diabetes Mellitus (T1DM). Restoration of beta-cell mass allows return to euglycaemia and insulin independence. We aimed to examine its impact on the secondary complications associated with severe T1DM including diabetic eye disease, neuropathy and cardiovascular disease.
Methods
A database search using MedLINE to identify publications to April 2023 was conducted. Searches were performed using MeSH terms ‘Pancreas Transplantation’ AND ‘Diabetes Mellitus, Type 1’ ‘Diabetic Retinopathy’ OR ‘Heart Disease’ OR ‘Cardiovascular Diseases’ OR ‘Peripheral Vascular Disease’ OR “Amputation’ OR ‘Neuropathy.”
Results
All articles were retrospective with 51.1 % (n = 23) case control studies and 48.9 % (n = 22) cohort studies. 82.2 % (n = 37) examined simultaneous pancreas and kidney (SPK) transplantation and 17.8 % (n = 8) analysed pancreas transplant alone (PTA). Heterogenous outcomes metrics were employed. 15 studies examined diabetic retinopathy (DR) with 53.3 % (n = 8) demonstrated improvements after PT, while the remainder (n = 7) exhibited stabilisation. 16 studies assessed neuropathy and 87.5 % (n = 14) demonstrated beneficial effects of PT on nerve conduction studies, vibration perception threshold or corneal confocal microscopy. There was a positive effect on cardiovascular disease by reduction in the incidence of cardiac events, improvement in metabolic profile and increased left ventricular ejection fraction. 14 studies examined cardiovascular disease (71.4 % (n = 10) improvement; 14.2 % (n = 2) stabilisation; 14.2 % (n = 2) progression).
Conclusion
SPK and PTA have beneficial effects in ameliorating or stabilising diabetes complications. Future work should seek to reduce heterogeneity of outcome metrics assessing T1DM complication profile to facilitate robust comparison of beta-cell replacement interventions.
{"title":"The impact of pancreas transplantation on diabetic complications: A systematic review","authors":"Gayathri Giri , Daniel Doherty , Shazli Azmi , Hussein Khambalia , Giuseppe Giuffrida , Zia Moinuddin , David van Dellen","doi":"10.1016/j.trre.2025.100910","DOIUrl":"10.1016/j.trre.2025.100910","url":null,"abstract":"<div><h3>Background</h3><div>Pancreas Transplantation (PT) provides optimal treatment for patients with severe complicated Type 1 Diabetes Mellitus (T1DM). Restoration of beta-cell mass allows return to euglycaemia and insulin independence. We aimed to examine its impact on the secondary complications associated with severe T1DM including diabetic eye disease, neuropathy and cardiovascular disease.</div></div><div><h3>Methods</h3><div>A database search using MedLINE to identify publications to April 2023 was conducted. Searches were performed using MeSH terms ‘Pancreas Transplantation’ AND ‘Diabetes Mellitus, Type 1’ ‘Diabetic Retinopathy’ OR ‘Heart Disease’ OR ‘Cardiovascular Diseases’ OR ‘Peripheral Vascular Disease’ OR “Amputation’ OR ‘Neuropathy.”</div></div><div><h3>Results</h3><div>All articles were retrospective with 51.1 % (<em>n</em> = 23) case control studies and 48.9 % (<em>n</em> = 22) cohort studies. 82.2 % (<em>n</em> = 37) examined simultaneous pancreas and kidney (SPK) transplantation and 17.8 % (<em>n</em> = 8) analysed pancreas transplant alone (PTA). Heterogenous outcomes metrics were employed. 15 studies examined diabetic retinopathy (DR) with 53.3 % (<em>n</em> = 8) demonstrated improvements after PT, while the remainder (<em>n</em> = 7) exhibited stabilisation. 16 studies assessed neuropathy and 87.5 % (<em>n</em> = 14) demonstrated beneficial effects of PT on nerve conduction studies, vibration perception threshold or corneal confocal microscopy. There was a positive effect on cardiovascular disease by reduction in the incidence of cardiac events, improvement in metabolic profile and increased left ventricular ejection fraction. 14 studies examined cardiovascular disease (71.4 % (<em>n</em> = 10) improvement; 14.2 % (<em>n</em> = 2) stabilisation; 14.2 % (n = 2) progression).</div></div><div><h3>Conclusion</h3><div>SPK and PTA have beneficial effects in ameliorating or stabilising diabetes complications. Future work should seek to reduce heterogeneity of outcome metrics assessing T1DM complication profile to facilitate robust comparison of beta-cell replacement interventions.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100910"},"PeriodicalIF":3.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049385","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}
Pub Date : 2025-01-09DOI: 10.1016/j.trre.2025.100909
Seokjoo Lee, Thomas H. Dohlman, Reza Dana
Immunology depends on maintaining a delicate balance within the human body, and disruptions can result in conditions such as autoimmune diseases, immunodeficiencies, and hypersensitivity reactions. This balance is especially crucial in transplantation immunology, where one of the primary challenges is preventing graft rejection. Such rejection can lead to organ failure, increased patient mortality, and higher healthcare costs due to the limited availability of donor tissues relative to patient needs. Xenotransplantation, like using porcine corneas for human transplants, offers a potential solution to the donor tissue shortage but faces substantial immunological rejection issues. To prevent rejection in both allo- and xenotransplantation, a deep understanding of how the body maintains immunological balance is essential, particularly since achieving tolerance to non-self tissues is considered the “holy grail” of the field. The cornea, the most frequently transplanted solid organ, has a high acceptance rate due to its immune-privileged status and serves as an ideal model for studying graft rejection mechanisms that disrupt tolerance. However, multiple immune pathways complicate our understanding of these mechanisms. This review examines the rejection mechanisms in corneal transplantation, identifying key cells involved and potential therapeutic strategies to induce and maintain immunological tolerance in both allo- and xenografts across various transplants.
{"title":"Immunology in corneal transplantation—From homeostasis to graft rejection","authors":"Seokjoo Lee, Thomas H. Dohlman, Reza Dana","doi":"10.1016/j.trre.2025.100909","DOIUrl":"10.1016/j.trre.2025.100909","url":null,"abstract":"<div><div>Immunology depends on maintaining a delicate balance within the human body, and disruptions can result in conditions such as autoimmune diseases, immunodeficiencies, and hypersensitivity reactions. This balance is especially crucial in transplantation immunology, where one of the primary challenges is preventing graft rejection. Such rejection can lead to organ failure, increased patient mortality, and higher healthcare costs due to the limited availability of donor tissues relative to patient needs. Xenotransplantation, like using porcine corneas for human transplants, offers a potential solution to the donor tissue shortage but faces substantial immunological rejection issues. To prevent rejection in both allo- and xenotransplantation, a deep understanding of how the body maintains immunological balance is essential, particularly since achieving tolerance to non-self tissues is considered the “holy grail” of the field. The cornea, the most frequently transplanted solid organ, has a high acceptance rate due to its immune-privileged status and serves as an ideal model for studying graft rejection mechanisms that disrupt tolerance. However, multiple immune pathways complicate our understanding of these mechanisms. This review examines the rejection mechanisms in corneal transplantation, identifying key cells involved and potential therapeutic strategies to induce and maintain immunological tolerance in both allo- and xenografts across various transplants.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100909"},"PeriodicalIF":3.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974252","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 : 2025-01-09DOI: 10.1016/j.trre.2025.100908
Daler Rahimov , Vivian Z. Yan , Danial Ahmad , Nayeem Nasher , Rob Tatum , Moses Im , Eugene Storozynsky , J. Eduardo Rame , Keshava Rajagopal , John W. Entwistle , Howard T. Massey , Vakhtang Tchantchaleishvili
Purpose
Patients with systemic amyloidosis with cardiac involvement require careful selection for heart transplantation (HTx) due to the associated poor outcomes. Large databases do not provide sufficient granularity to allow for differentiation between its major subtypes [light-chain (AL) and transthyretin (ATTR) amyloidosis]. We sought to pool the existing data on amyloidosis patients undergoing HTx, and perform stratified analysis based on its major subtypes.
Methods
Electronic search identified adult patients with amyloidosis undergoing HTx. Cohort-level data for 340 patients from 19 studies were extracted and analyzed. Patients were categorized based on amyloid subtype into AL and ATTR groups.
Results
AL amyloidosis was diagnosed at an earlier age compared to ATTR [53 (95 % CI 48; 57) years vs. 63 (55; 71) years, p = 0.03], with greater incidence in the Caucasian population [75 % (60; 87) vs. 39 % (21; 59), p ≤0.01]. Females comprised 33 % (25; 41) of the patients with greater preponderance in AL group [41 % (33; 48) vs. 21 % (8; 36), p = 0.02]. AL patients also had higher involvement of ≥two organs [50 % (29; 70) vs. 15 % (3; 32), p = 0.01]. GI involvement [25 % (6; 50) vs. 0 % (0; 8), p = 0.02], and renal involvement [20 % (8; 34) vs. 0 % (0; 2), p < 0.01] were virtually limited to AL, while ATTR patients had more implantable cardioverter defibrillators placed [64 % (34; 90) vs. 15 % (6; 28), p < 0.01] and trended towards greater incidence of neuropathy [24 % (9; 42) vs. 9 % (2; 19), p = 0.07]. The AL group had a significantly higher incidence of recurrent amyloidosis [16 % (7; 27) vs. 0 % (0; 0), p ≤0.01]. Pooled Kaplan-Meier survival analysis showed worse long-term survival in the AL group (p = 0.02).
Conclusion
Patients with AL amyloidosis showed more widespread systemic involvement and worse long-term survival after HTx compared to patients with ATTR amyloidosis. Protocols for mitigating the recurrence of AL amyloidosis are needed to improve survival in this high-risk subtype.
{"title":"Characteristics and outcomes of cardiac amyloid disease after heart transplantation: A systematic review and meta-analysis","authors":"Daler Rahimov , Vivian Z. Yan , Danial Ahmad , Nayeem Nasher , Rob Tatum , Moses Im , Eugene Storozynsky , J. Eduardo Rame , Keshava Rajagopal , John W. Entwistle , Howard T. Massey , Vakhtang Tchantchaleishvili","doi":"10.1016/j.trre.2025.100908","DOIUrl":"10.1016/j.trre.2025.100908","url":null,"abstract":"<div><h3>Purpose</h3><div>Patients with systemic amyloidosis with cardiac involvement require careful selection for heart transplantation (HTx) due to the associated poor outcomes. Large databases do not provide sufficient granularity to allow for differentiation between its major subtypes [light-chain (AL) and transthyretin (ATTR) amyloidosis]. We sought to pool the existing data on amyloidosis patients undergoing HTx, and perform stratified analysis based on its major subtypes.</div></div><div><h3>Methods</h3><div>Electronic search identified adult patients with amyloidosis undergoing HTx. Cohort-level data for 340 patients from 19 studies were extracted and analyzed. Patients were categorized based on amyloid subtype into AL and ATTR groups.</div></div><div><h3>Results</h3><div>AL amyloidosis was diagnosed at an earlier age compared to ATTR [53 (95 % CI 48; 57) years vs. 63 (55; 71) years, <em>p</em> = 0.03], with greater incidence in the Caucasian population [75 % (60; 87) vs. 39 % (21; 59), <em>p</em> ≤0.01]. Females comprised 33 % (25; 41) of the patients with greater preponderance in AL group [41 % (33; 48) vs. 21 % (8; 36), <em>p</em> = 0.02]. AL patients also had higher involvement of ≥two organs [50 % (29; 70) vs. 15 % (3; 32), <em>p</em> = 0.01]. GI involvement [25 % (6; 50) vs. 0 % (0; 8), <em>p</em> = 0.02], and renal involvement [20 % (8; 34) vs. 0 % (0; 2), <em>p</em> < 0.01] were virtually limited to AL, while ATTR patients had more implantable cardioverter defibrillators placed [64 % (34; 90) vs. 15 % (6; 28), p < 0.01] and trended towards greater incidence of neuropathy [24 % (9; 42) vs. 9 % (2; 19), <em>p</em> = 0.07]. The AL group had a significantly higher incidence of recurrent amyloidosis [16 % (7; 27) vs. 0 % (0; 0), <em>p</em> ≤0.01]. Pooled Kaplan-Meier survival analysis showed worse long-term survival in the AL group (<em>p</em> = 0.02).</div></div><div><h3>Conclusion</h3><div>Patients with AL amyloidosis showed more widespread systemic involvement and worse long-term survival after HTx compared to patients with ATTR amyloidosis. Protocols for mitigating the recurrence of AL amyloidosis are needed to improve survival in this high-risk subtype.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 2","pages":"Article 100908"},"PeriodicalIF":3.6,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143145438","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 : 2025-01-01DOI: 10.1016/j.trre.2024.100899
Maria Meritxell Roca Mora , Andre Milani Reis , Filipe Piazzi Tavares , Lídia Santos Oliveira , Amanda Godoi , Patricia Viana , Juliano Riella
Introduction
Direct-acting oral anticoagulants (DOACs) have recently shown potential efficacy for many conditions without the need for regular monitoring. However, their use in kidney transplant recipients (KTRs) is controversial, with no clear consensus on how they compare to vitamin K antagonists (VKAs), which have traditionally been used as preferred anticoagulation therapy in these patients.
Methods
PubMed, Cochrane Central, and Embase databases were systematically searched up to December 2023 for studies comparing DOACs versus VKAs in KTRs. The main outcomes of interest included venous thromboembolism (VTE), major bleeding, graft failure, mortality, and changes in estimated glomerular filtration rate (eGFR). Statistical analyses were performed using RStudio 4.1.2 software. PROSPERO ID: CRD42024498423.
Results
Five studies with a total of 959 participants were included. Of these, 433 (45.15 %) participants were treated with DOACs. The mean age of participants was 60.05 years, and 65.9 % were male. The use of DOACs in KTRs was associated with a significant reduction in major bleeding (RR 0.56; 95 % CI 0.35 to 0.90; p = 0.02; I2 = 0 %) and mortality (RR 0.49; 95 % CI 0.33 to 0.74; p = 0.0006; I2 = 0 %). No significant differences were found between groups in VTE (RR 0.82; 95 % CI 0.47 to 1.43; p = 0.48; I2 = 12 %), graft failure (RR 0.43; 95 % CI 0.14 to 1.27; p = 0.13; I2 = 52 %), and eGFR (MD 3.72 mL/Kg/1.73 m2; 95 % CI -1.58 to 9.03; p = 0.17; I2 = 0 %). Evidence quality for some outcomes remains low to moderate, limiting the confidence in these conclusions.
Conclusion
Our meta-analysis suggests that DOACs represent an effective anticoagulation strategy in KTR, with a significant reduction in major bleeding and mortality relative to VKA.
{"title":"Safety and efficacy of direct oral anticoagulants in kidney transplant recipients: A systematic review and meta-analysis","authors":"Maria Meritxell Roca Mora , Andre Milani Reis , Filipe Piazzi Tavares , Lídia Santos Oliveira , Amanda Godoi , Patricia Viana , Juliano Riella","doi":"10.1016/j.trre.2024.100899","DOIUrl":"10.1016/j.trre.2024.100899","url":null,"abstract":"<div><h3>Introduction</h3><div>Direct-acting oral anticoagulants (DOACs) have recently shown potential efficacy for many conditions without the need for regular monitoring. However, their use in kidney transplant recipients (KTRs) is controversial, with no clear consensus on how they compare to vitamin K antagonists (VKAs), which have traditionally been used as preferred anticoagulation therapy in these patients.</div></div><div><h3>Methods</h3><div>PubMed, Cochrane Central, and Embase databases were systematically searched up to December 2023 for studies comparing DOACs versus VKAs in KTRs. The main outcomes of interest included venous thromboembolism (VTE), major bleeding, graft failure, mortality, and changes in estimated glomerular filtration rate (eGFR). Statistical analyses were performed using RStudio 4.1.2 software. PROSPERO ID: CRD42024498423.</div></div><div><h3>Results</h3><div>Five studies with a total of 959 participants were included. Of these, 433 (45.15 %) participants were treated with DOACs. The mean age of participants was 60.05 years, and 65.9 % were male. The use of DOACs in KTRs was associated with a significant reduction in major bleeding (RR 0.56; 95 % CI 0.35 to 0.90; <em>p</em> = 0.02; I<sup>2</sup> = 0 %) and mortality (RR 0.49; 95 % CI 0.33 to 0.74; <em>p</em> = 0.0006; I<sup>2</sup> = 0 %). No significant differences were found between groups in VTE (RR 0.82; 95 % CI 0.47 to 1.43; <em>p</em> = 0.48; I<sup>2</sup> = 12 %), graft failure (RR 0.43; 95 % CI 0.14 to 1.27; <em>p</em> = 0.13; I<sup>2</sup> = 52 %), and eGFR (MD 3.72 mL/Kg/1.73 m2; 95 % CI -1.58 to 9.03; <em>p</em> = 0.17; I<sup>2</sup> = 0 %). Evidence quality for some outcomes remains low to moderate, limiting the confidence in these conclusions.</div></div><div><h3>Conclusion</h3><div>Our meta-analysis suggests that DOACs represent an effective anticoagulation strategy in KTR, with a significant reduction in major bleeding and mortality relative to VKA.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 1","pages":"Article 100899"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857408","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 : 2025-01-01DOI: 10.1016/j.trre.2024.100900
Michael Corr , Andrew Walker , Alexander P. Maxwell , Gareth J. McKay
Background
Rejection and graft failure remain common in kidney transplant recipients. Non-adherence to immunosuppressive medications is considered a major contributary factor to reduced long-term graft survival, particularly in younger people. Improvements in clinical practice based on adherence studies has been minimal.
Methods
Joanna Briggs' Institute Methodology was used. MedlineALL, Embase, Web of Science Core Collection and Scopus databases were searched from January 2000 through to December 2023. Abstract and full text reviews were undertaken independently by two reviewers. Data was collated using a pre-designed extraction tool.
Results
359 articles met the inclusion criteria. Non-adherence was commonly defined using self-reported questionnaires or pharmacy re-fill rates. Prevalence of non-adherence varied widely. There was little correlation between method of measurement and reported rates of non-adherence. Despite younger age being identified as a risk factor for non-adherence, pooled reported prevalence did not differ significantly in studies reporting prevalence in children, adolescents, or young adults vs. older adults (36.0 % vs. 34.0 %). Interventional studies to detect or improve adherence are highly heterogenous, often report small effects and are limited by the lack of gold-standard methods to measure adherence.
Discussion
This scoping review outlines the complexities of non-adherence to immunosuppressive medications among kidney transplant recipients, highlighting significant variability in adherence definitions, measurements, and intervention efficacy. Reported non-adherence rates vary widely (2–89 %), underscoring the need for standardisation of the definition of non-adherence in research. Findings suggest that non-adherence to immunosuppressive medication is driven by a mix of demographic, psychosocial, and transplant-specific factors. Future research should prioritise standardised definitions of adherence, validated tools to measure adherence, and focus on clinically significant outcomes in non-adherent populations to develop meaningful, impactful interventions for long-term patient benefit.
背景:排斥反应和移植物衰竭在肾移植受者中仍然很常见。不坚持使用免疫抑制药物被认为是导致移植物长期存活率降低的主要因素,尤其是在年轻人中。基于依从性研究的临床实践的改进一直很小。方法:采用Joanna Briggs研究所的方法。检索了2000年1月至2023年12月期间的MedlineALL、Embase、Web of Science Core Collection和Scopus数据库。摘要和全文评审由两位审稿人独立进行。使用预先设计的提取工具对数据进行整理。结果:359篇文章符合纳入标准。非依从性通常通过自我报告的问卷或药房重新填充率来定义。不依从的发生率差别很大。测量方法与报告的不依从率之间几乎没有相关性。尽管较年轻的年龄被确定为不依从性的危险因素,但在报告儿童、青少年或年轻人与老年人患病率的研究中,汇总报告的患病率没有显着差异(36.0%对34.0%)。检测或改善依从性的介入研究是高度异质性的,通常报告的效果很小,并且由于缺乏衡量依从性的金标准方法而受到限制。讨论:本综述概述了肾移植受者免疫抑制药物不依从性的复杂性,强调了依从性定义、测量和干预效果的显著差异。报告的不依从率差异很大(2- 89%),强调了研究中不依从定义标准化的必要性。研究结果表明,不坚持使用免疫抑制药物是由人口统计学、社会心理和移植特异性因素共同驱动的。未来的研究应优先考虑依从性的标准化定义,有效的工具来衡量依从性,并将重点放在非依从性人群的临床显著结果上,以开发有意义的、有效的干预措施,以获得长期患者利益。
{"title":"Non-adherence to immunosuppressive medications in kidney transplant recipients- a systematic scoping review","authors":"Michael Corr , Andrew Walker , Alexander P. Maxwell , Gareth J. McKay","doi":"10.1016/j.trre.2024.100900","DOIUrl":"10.1016/j.trre.2024.100900","url":null,"abstract":"<div><h3>Background</h3><div>Rejection and graft failure remain common in kidney transplant recipients. Non-adherence to immunosuppressive medications is considered a major contributary factor to reduced long-term graft survival, particularly in younger people. Improvements in clinical practice based on adherence studies has been minimal.</div></div><div><h3>Methods</h3><div>Joanna Briggs' Institute Methodology was used. MedlineALL, Embase, Web of Science Core Collection and Scopus databases were searched from January 2000 through to December 2023. Abstract and full text reviews were undertaken independently by two reviewers. Data was collated using a pre-designed extraction tool.</div></div><div><h3>Results</h3><div>359 articles met the inclusion criteria. Non-adherence was commonly defined using self-reported questionnaires or pharmacy re-fill rates. Prevalence of non-adherence varied widely. There was little correlation between method of measurement and reported rates of non-adherence. Despite younger age being identified as a risk factor for non-adherence, pooled reported prevalence did not differ significantly in studies reporting prevalence in children, adolescents, or young adults vs. older adults (36.0 % vs. 34.0 %). Interventional studies to detect or improve adherence are highly heterogenous, often report small effects and are limited by the lack of gold-standard methods to measure adherence.</div></div><div><h3>Discussion</h3><div>This scoping review outlines the complexities of non-adherence to immunosuppressive medications among kidney transplant recipients, highlighting significant variability in adherence definitions, measurements, and intervention efficacy. Reported non-adherence rates vary widely (2–89 %), underscoring the need for standardisation of the definition of non-adherence in research. Findings suggest that non-adherence to immunosuppressive medication is driven by a mix of demographic, psychosocial, and transplant-specific factors. Future research should prioritise standardised definitions of adherence, validated tools to measure adherence, and focus on clinically significant outcomes in non-adherent populations to develop meaningful, impactful interventions for long-term patient benefit.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 1","pages":"Article 100900"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142789667","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}
Pub Date : 2025-01-01DOI: 10.1016/j.trre.2024.100880
Gavin G. Calpin , Cian Hehir , Matthew G. Davey , Benjamin M. MacCurtain , Dilly Little , Niall F. Davis
Introduction
The left kidney is preferable in living donor nephrectomy (LDN). We aimed to investigate the safety and efficacy of right versus left LDN in both donor and recipients. A subgroup analysis of outcomes based on operative approach was also performed.
Methods
A systematic review and meta-analysis was performed as per PRISMA guidelines. Outcomes of interest were extracted from included studies and analysed.
Results
There were 31 studies included with 79,912 transplants. Left LDN was performed in 84.1 % of cases and right LDN in 15.9 %. Right LDN was associated with reduced EBL (P = 0.010), intra-operative complications (P = 0.030) and operative time (P = 0.006), but higher rates of conversion to open surgery (1.4 % vs 0.9 %). However, right living donor renal transplantation (LDRT) had higher rates of delayed graft function (5.4 % vs 4.2 %, P < 0.0001) and graft loss (2.6 % vs 1.1 %, P < 0.0001). Graft survival was reduced in right LDRT at 3 years (92.0 % vs 94.2 %, P = 0.001) but comparable to left LDRT at 1- and 5-years. Otherwise, donor and recipient peri-operative outcomes and serum creatinine levels were comparable in both groups. Hand-assisted LDN was associated with shorter warm ischaemia time (P < 0.0001) but longer length of stay (LOS) than laparoscopic LDN and robotic-assisted LDN (P < 0.0001). RA-LDN was associated with less EBL and shorter LOS (both P < 0.0001) while patients who underwent L-LDN had a lower mean serum creatinine (SCr) level on discharge (P < 0.0001).
Conclusion
Right LDRT has higher rates of delayed graft function and graft loss compared to left LDRT. Minimally-invasive surgical approaches potentially offer improved outcomes but further large-scale randomised controlled trials studies are required to confirm this finding.
{"title":"Right and left living donor nephrectomy and operative approach: A systematic review and meta-analysis of donor and recipient outcomes","authors":"Gavin G. Calpin , Cian Hehir , Matthew G. Davey , Benjamin M. MacCurtain , Dilly Little , Niall F. Davis","doi":"10.1016/j.trre.2024.100880","DOIUrl":"10.1016/j.trre.2024.100880","url":null,"abstract":"<div><h3>Introduction</h3><div>The left kidney is preferable in living donor nephrectomy (LDN). We aimed to investigate the safety and efficacy of right versus left LDN in both donor and recipients. A subgroup analysis of outcomes based on operative approach was also performed.</div></div><div><h3>Methods</h3><div>A systematic review and meta-analysis was performed as per PRISMA guidelines. Outcomes of interest were extracted from included studies and analysed.</div></div><div><h3>Results</h3><div>There were 31 studies included with 79,912 transplants. Left LDN was performed in 84.1 % of cases and right LDN in 15.9 %. Right LDN was associated with reduced EBL (<em>P</em> = 0.010), intra-operative complications (<em>P</em> = 0.030) and operative time (<em>P</em> = 0.006), but higher rates of conversion to open surgery (1.4 % vs 0.9 %). However, right living donor renal transplantation (LDRT) had higher rates of delayed graft function (5.4 % vs 4.2 %, <em>P</em> < 0.0001) and graft loss (2.6 % vs 1.1 %, <em>P</em> < 0.0001). Graft survival was reduced in right LDRT at 3 years (92.0 % vs 94.2 %, <em>P</em> = 0.001) but comparable to left LDRT at 1- and 5-years. Otherwise, donor and recipient peri-operative outcomes and serum creatinine levels were comparable in both groups. Hand-assisted LDN was associated with shorter warm ischaemia time (<em>P</em> < 0.0001) but longer length of stay (LOS) than laparoscopic LDN and robotic-assisted LDN (<em>P</em> < 0.0001). RA-LDN was associated with less EBL and shorter LOS (both <em>P</em> < 0.0001) while patients who underwent L-LDN had a lower mean serum creatinine (SCr) level on discharge (<em>P</em> < 0.0001).</div></div><div><h3>Conclusion</h3><div>Right LDRT has higher rates of delayed graft function and graft loss compared to left LDRT. Minimally-invasive surgical approaches potentially offer improved outcomes but further large-scale randomised controlled trials studies are required to confirm this finding.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 1","pages":"Article 100880"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142147282","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}
Pub Date : 2024-11-26DOI: 10.1016/j.trre.2024.100897
Pooja Lokkur , Shyam Bihari Bansal
Transplantation is the treatment of choice in most patients with kidney failure. The complement system plays a vital role in transplantation. The complement system forms a major part of innate immunity and acts as a bridge between innate and acquired immunity. Many diseases, particularly concerning the kidneys, result from complement system dysregulation, like atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3GN), systemic lupus erythematosus (SLE and some other immune complex diseases. The complement system activation is a very important part of post-transplant events like ischemia-reperfusion injury (IRI), delayed graft function (DGF), antibody-mediated rejection (ABMR) and thrombotic microangiopathy (TMA). A better understanding of the complement cascade can help to plan strategies to prevent and manage complement-related problems before and after kidney transplantation. Many newer molecules are either being developed or in the pipeline, which target the complement system at various stages. These novel therapeutics are now considered additional measures to improve graft survival. This review summarises the complement cascade, its role in kidney diseases and kidney transplantation, and possible areas of target and novel therapeutics.
{"title":"Complement in Kidney Transplantation","authors":"Pooja Lokkur , Shyam Bihari Bansal","doi":"10.1016/j.trre.2024.100897","DOIUrl":"10.1016/j.trre.2024.100897","url":null,"abstract":"<div><div>Transplantation is the treatment of choice in most patients with kidney failure. The complement system plays a vital role in transplantation. The complement system forms a major part of innate immunity and acts as a bridge between innate and acquired immunity. Many diseases, particularly concerning the kidneys, result from complement system dysregulation, like atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3GN), systemic lupus erythematosus (SLE and some other immune complex diseases. The complement system activation is a very important part of post-transplant events like ischemia-reperfusion injury (IRI), delayed graft function (DGF), antibody-mediated rejection (ABMR) and thrombotic microangiopathy (TMA). A better understanding of the complement cascade can help to plan strategies to prevent and manage complement-related problems before and after kidney transplantation. Many newer molecules are either being developed or in the pipeline, which target the complement system at various stages. These novel therapeutics are now considered additional measures to improve graft survival. This review summarises the complement cascade, its role in kidney diseases and kidney transplantation, and possible areas of target and novel therapeutics.</div></div>","PeriodicalId":48973,"journal":{"name":"Transplantation Reviews","volume":"39 1","pages":"Article 100897"},"PeriodicalIF":3.6,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748171","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}