Transplantation最新文献

{"title":"The Effect of Adding Dapagliflozin on Chronic Renal Allograft Dysfunction: A Randomized, Prospective, Double-blind, Placebo-controlled Trial.","authors":"Elias David-Neto, Alberto Elias Ribeiro David, Bruna Alves, Jose Otto Reusing, Carolina Lembe, Nelson Zocoler Galante, Rayra Silva, Patricia Soares de Souza, Monica Nakamura, Helio Tedesco Silva","doi":"10.1097/TP.0000000000005741","DOIUrl":"https://doi.org/10.1097/TP.0000000000005741","url":null,"abstract":"<p><strong>Background: </strong>Chronic allograft dysfunction (CAD) remains a leading cause of graft loss after kidney transplantation. Dapagliflozin (DAPA) has shown renal and cardiometabolic benefits in nontransplanted patients with chronic kidney disease. However, data on recipients with CAD are lacking.</p><p><strong>Methods: </strong>Adult kidney transplant recipients (n = 208), with estimated glomerular filtration rate (eGFR) 25-45 mL/min/1.73 m2 or 45-60 mL/min/1.73 m2 with ≥10% annual decline, were randomized to receive DAPA 10 mg/d or placebo for 12 mo. The outcomes were differences in eGFR, in eGFR slopes, proteinuria, blood pressure, body mass index (BMI), and safety.</p><p><strong>Results: </strong>There was no difference in eGFR between groups (P = 0.611). However, at month 12, eGFR was higher in the PLACEBO group (n = 102; 39.4 ± 0.9 vs 36.5 ± 0.9 mL/min/1.73 m2 (P = 0.029). In the DAPA group (n = 106), the least square means (LSM) of eGFR slopes was -0.86 ± 0.65 mL/min/1.73 m2 at the third month while remaining at -0.75 ± 0.65 mL/min/1.73 m2 at 12 mo. The PLACEBO group presented an LSM slope of -0.34 ± 067 mL/min/1.73 m2 at 3 mo and +0.51 ± 66 mL/min/1.73 m2 at 12 mo. In a per-protocol analysis, patients in the DAPA group (n = 86) under angiotensin-converting enzyme inhibitor/ angiotensin receptor blockers (n = 23) did not present an eGFR dip, but those not under angiotensin-converting enzyme inhibitor/ angiotensin receptor blockers (n = 63) did. DAPA reduced proteinuria from 267 to 84 mg/g (P < 0.001), body weight by 2 kg (P = 0.02), BMI by 0.7 kg/m2 (P = 0.023), systolic blood pressure by 7 mm Hg (P = 0.014), diastolic blood pressure from baseline to 9 mo (80.5 ± 1.2 vs 76.8 ± 1.2 mm Hg, P = 0.021), and glycated hemoglobin in patients with diabetes by 0.5% (P = 0.04). The incidence of serious adverse events did not differ between groups.</p><p><strong>Conclusions: </strong>In kidney transplant recipients with CAD, DAPA did not improve eGFR compared with placebo, but presented reductions in proteinuria, blood pressure, BMI, and glycated hemoglobin, with acceptable safety.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Initial Kidney Graft Function on Long-term Outcomes: A Matter of Definition?","authors":"Umberto Maggiore, Paolo Cravedi","doi":"10.1097/TP.0000000000005722","DOIUrl":"https://doi.org/10.1097/TP.0000000000005722","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk Profiles and Outcomes in Living Donor Liver Transplantation Recipients Aged 70 y and Older: A Korean National Registry Analysis.","authors":"Deok-Gie Kim, Mun Chae Choi, Shin Hwang, Kwang-Woong Lee, Jongman Kim, Donglak Choi, Je Ho Ryu, Bong-Wan Kim, Dong-Sik Kim, Hae Won Lee, Yang Won Nah, Man Ki Ju, Tae-Seok Kim, Soo Jin Na Choi, Young Kyoung You, Dong Jin Joo","doi":"10.1097/TP.0000000000005716","DOIUrl":"https://doi.org/10.1097/TP.0000000000005716","url":null,"abstract":"<p><strong>Background: </strong>As the global population ages, older-aged candidates increasingly undergo living donor liver transplantation (LDLT). Outcomes and risk factors in recipients aged ≥70 y remain unclear. This study assessed graft survival and age-specific risk factors using nationwide registry data.</p><p><strong>Methods: </strong>From the Korean Organ Transplantation Registry, 4802 adult LDLT recipients were categorized into age <70 (n = 4660) and age ≥70 (n = 142) groups. Graft survival was analyzed using Kaplan-Meier and multivariable Cox regression to evaluate real-world outcomes. Propensity score matching was additionally performed as a sensitivity analysis to confirm the robustness of the findings. Subgroup analyses were used to identify risk factors specific to the age ≥70 group.</p><p><strong>Results: </strong>In unmatched analyses, recipients aged ≥70 y demonstrated significantly lower graft survival than younger recipients (5-y survival: 74.4% versus 87.2%; P < 0.001). However, after multivariable adjustment, age ≥70 was not an independent predictor of graft loss (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 0.83-1.87; P = 0.29). Similar findings were observed in the propensity-matched cohort. Subgroup analyses demonstrated that, among recipients aged ≥70 y, pretransplant hospitalization (adjusted hazard ratio [aHR], 1.94; 95% CI, 1.14-3.29), graft steatosis ≥5% (aHR, 1.74; 95% CI, 1.03-2.95), and vascular complications (aHR, 3.11; 95% CI, 1.31-7.43) were each associated with significantly elevated risk of graft failure.</p><p><strong>Conclusions: </strong>Chronological age alone did not independently predict graft failure, but age ≥70 y may amplify risk when combined with steatosis, pretransplant hospitalization, or vascular complications. Therefore, LDLT eligibility in elderly candidates may be better guided by clinical risk profiling rather than age alone.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Decade of Progress in Uterus Transplantation in the United States: Results From the World Transplant Congress 2025.","authors":"Paige M Porrett, Liza Johannesson","doi":"10.1097/TP.0000000000005746","DOIUrl":"https://doi.org/10.1097/TP.0000000000005746","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Impact of Probabilistic Survival Information on Kidney Accept/Decline Decisions: A Survey of the National Kidney Foundation's Community.","authors":"Diwakar Gupta, Paola Martin, Timothy L Pruett","doi":"10.1097/TP.0000000000005737","DOIUrl":"https://doi.org/10.1097/TP.0000000000005737","url":null,"abstract":"<p><strong>Background: </strong>Decisions to accept or decline kidney offers hinge on candidates and clinician's expectations of post-transplant outcomes. Yes, no study has quantified the impact of information provided to candidates on the willingness to accept a kidney for transplantation.</p><p><strong>Methods: </strong>National Kidney Foundation members who were either waitlisted or had received a kidney transplant were surveyed to quantify the impact of probabilistic post-transplant survival information on acceptance of kidneys offered for transplant. Survey participants were randomly assigned to 3 groups with similar proportions of (self-identified) White, Black, and other race people, age distribution, and whether the participant received a transplant or was waitlisted. Each participant group received a different hypothetical kidney offer with different donor quality (12%, 48%, and 85% kidney donor profile index, respectively).</p><p><strong>Results: </strong>Participants' responses were recorded first with only 1-y post-transplant survival information and subsequently with 5- and 10-y survival probabilities. Participants' level of confidence in their responses and factors most important to them when making acceptance decisions were also recorded. With 1-y survival information 79%, 73%, and 55% of participants accepted offers 1, 2, and 3, respectively. With additional 5- and 10-y survival information, the acceptance rates increased to 88%, 86%, and 73% for each of the 3 offers (P < 0.001).</p><p><strong>Conclusions: </strong>Participants frequently identified the likelihood of the kidney surviving 5 and 10 y as being the most important information in choosing their acceptance decisions.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Pharmacokinetics, and Pharmacodynamics of Fixed-dose, Subcutaneous, and Intravenous Administration of VEL-101, an Anti-CD28 PEGylated Monoclonal Antibody Fragment, in Healthy Participants: A Randomized, Double-blind, Placebo-controlled, Dose Escalation, Phase 1 Study.","authors":"Simon Tremblay, Ana Abaigar, Pamela Allton, Duarte Sardinha, Samir J Patel, Kamal Shah, James Maynard, Babatunde Otulana","doi":"10.1097/TP.0000000000005701","DOIUrl":"https://doi.org/10.1097/TP.0000000000005701","url":null,"abstract":"<p><strong>Background: </strong>VEL-101, also known as pegrizeprument, is a monovalent, humanized, anti-CD28 PEGylated monoclonal antibody fragment that selectively blocks CD28 costimulation, under development as a maintenance immunosuppressant in kidney transplant recipients. In development as a fixed-dose subcutaneous maintenance immunosuppressant in kidney transplant recipients, the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of VEL-101 were evaluated in this randomized, double-blind, placebo-controlled, dose escalation, phase 1 study (NCT05238493).</p><p><strong>Methods: </strong>Sixty healthy participants were randomly assigned 3:1 to receive 1 of 7 dose levels of VEL-101 or placebo (2 intravenous and 5 subcutaneous) and followed for 50 d. Safety, pharmacokinetic, and pharmacodynamic analyses evaluated the nature and severity of treatment-emergent adverse events, serum VEL-101 levels, and CD28 receptor occupancy, respectively.</p><p><strong>Results: </strong>Most adverse events were mild to moderate, with injection site pain the most frequently reported. One serious adverse event (rhabdomyolysis, grade 3) resolved with supportive care. No case of clinically elevated cytokines or cytokine release syndrome was observed. Following subcutaneous administration, all participants had detectable serum concentrations of VEL-101. Dose-exposure proportionality was maintained, and VEL-101 elimination was consistent regardless of subcutaneous or intravenous administration.</p><p><strong>Conclusions: </strong>Subcutaneous administration of VEL-101 resulted in dose-proportional increases in maximum concentration and area under the time-concentration curve0-inf across the doses tested and a sustained receptor occupancy of ≥50% to ≥80%. Subcutaneous administration of VEL-101 was generally well-tolerated, yielding detectable CD28 receptor occupancy levels acceptable for future study in kidney transplant recipients.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alveolus-on-a-Chip: A Novel Tool for Modeling Lung Transplant Cold Storage Ischemia/Reperfusion Injury.","authors":"Logan Langerude, Blake Gill, Griffin Taylor, Kunal Patel, Satish Nadig, Jason McCarthy, Jennifer Mulligan, ZhenXiao Tu, Carl Atkinson","doi":"10.1097/TP.0000000000005682","DOIUrl":"https://doi.org/10.1097/TP.0000000000005682","url":null,"abstract":"<p><strong>Background: </strong>Current in vitro models used to investigate lung transplant cold storage (CS) ischemia/reperfusion injury (IRI) use single-cell lines in static culture. Although these models have informed our understanding of CS-IRI, they lack physiological complexity. We hypothesized that using a lung alveolus-on-a-chip model would facilitate the development of more physiologically relevant CS-IRI in vitro models.</p><p><strong>Methods: </strong>We used the Emulate Organ-on-a-Chip 3-dimensional microfluidic air-liquid interface alveolus-on-a-chip model seeded with human primary alveolar epithelial cells and human lung microvascular endothelial cells. To simulate CS and IRI, alveolus chips were removed from the perfusion, and endothelial channels were perfused with Perfadex and stored at 4 °C for 6 h to recapitulate CS. Following CS, alveolar chips were reperfused under laminar media flow and stretch conditions for 24 h at 37 °C to simulate IRI. The impact of CS-IRI was compared with that of control alveolus chips using immunofluorescent staining for cellular markers, chemokine/adhesion molecule arrays to assess epithelial and endothelial injury/activation, and mRNA collected for NanoString analysis.</p><p><strong>Results: </strong>Brightfield imaging and immunostaining indicated a loss of barrier function after CS-IRI. Assessment of chemokines and adhesion molecules demonstrated significant increases in markers of inflammation. NanoString analysis identified 42 human primary alveolar epithelial cell and 49 human lung microvascular endothelial cell genes that were significantly differentially expressed between the normal and CS-IRI groups (P < 0.01).</p><p><strong>Conclusions: </strong>Here, we report a novel CS-IRI model that incorporates physiological flow, stretch, and cell-cell interactions. We demonstrated key changes associated with IRI and hypothesized that future studies will provide novel insights into the pathophysiology of CS-IRI post-lung transplantation.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A New Costimulatory Blockage Agent in the Pipeline.","authors":"Enver Akalin","doi":"10.1097/TP.0000000000005733","DOIUrl":"https://doi.org/10.1097/TP.0000000000005733","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Declining All-cause Allograft Survival in the Modern era: A 50-y Single-center Consecutive Cohort Study.","authors":"Elijah Wiebe, Robert Balshaw, Kaleb Chartier, Ian W Gibson, Julie Ho, Jamie Shaw, Martin Karpinski, Aaron Trachtenberg, Denise Pochinco Mlt, Aviva Goldberg, Patricia Birk, Maury Pinsk, David N Rush, Peter W Nickerson, Chris Wiebe","doi":"10.1097/TP.0000000000005740","DOIUrl":"https://doi.org/10.1097/TP.0000000000005740","url":null,"abstract":"<p><strong>Background: </strong>Kidney transplantation outcomes have improved in the short term, but long-term graft survival gains have plateaued. Aging donors and recipients with increasing comorbidities may alter contemporary allograft outcomes.</p><p><strong>Methods: </strong>We retrospectively analyzed 2076 consecutive kidney transplants performed at a single Canadian center from 1969 to 2024, representing up to 50 y of complete follow-up. All-cause graft survival (ACGS) and death-censored graft survival were compared across 5 transplant eras using era-stratified Cox regression.</p><p><strong>Results: </strong>The median recipient age increased significantly across the eras from 35 to 54 y (P < 0.01) and the donor age from 28 to 45 y (P < 0.01), paralleled by 3-5-fold increases in pretransplant diabetes and obesity. Death-censored graft survival improved through the early 2000s but has since plateaued, whereas ACGS declined in the modern era (2018-2024) compared with the 1998-2009 peak (P = 0.007). Death with function accounted for >60% of graft losses in recent years, with infectious deaths rising from 21% to 45% (P < 0.01). Increasing donor and recipient age, comorbidities, and delayed graft function independently predicted inferior survival.</p><p><strong>Conclusions: </strong>These findings reveal a reversal in ACGS gains in the contemporary era, highlighting the need for precision immunosuppression strategies tailored to the aging, comorbid transplant population.</p>","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Mitochondrial Vulnerability During Prolonged Cold Ischemia.","authors":"Christoph Knosalla, Anna Stegmann","doi":"10.1097/TP.0000000000005669","DOIUrl":"10.1097/TP.0000000000005669","url":null,"abstract":"","PeriodicalId":23316,"journal":{"name":"Transplantation","volume":" ","pages":"e975-e976"},"PeriodicalIF":5.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228430","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}