Pub Date : 2023-10-30DOI: 10.3389/frtra.2023.1165320
C. Dudreuilh, S. Basu, O. Shaw, H. Burton, N. Mamode, F. Harris, T. Tree, P. Nedyalko, M. Terranova-Barberio, G. Lombardi, C. Scottà, A. Dorling
Introduction Highly sensitised (HS) patients represent up to 30% of patients on the kidney transplant waiting list. When they are transplanted, they have a high risk of acute/chronic rejection and long-term allograft loss. Regulatory T cells (Tregs) (CD4 + CD25 hi CD127 lo ) are T cells involved in the suppression of immune alloresponses. A particular subset, called T follicular regulatory T cells (Tfr, CXCR5 + Bcl-6 + ), is involved in regulating interactions between T effectors and B cells within the germinal centre and can be found in peripheral blood. Therefore, we wanted to identify specific subsets of Tregs in the peripheral blood of HS individuals. Methods We recruited prospectively healthy volunteers (HV) ( n = 9), non-sensitised patients on haemodialysis (HD) ( n = 9) and HS individuals, all of whom were on haemodialysis ( n = 15). Results We compared the Treg phenotypes of HV, HD and HS. HS patients had more CD161 + Tregs ( p = 0.02) and more CD45RA − CCR7 − T effectors (Teffs) ( p = 0.04, memory Teffs able to home to the germinal centre) compared to HVs. HS patients had more Bcl-6 + Tregs ( p < 0.05), fewer Th1-like Tregs, more Th2-like Tregs ( p < 0.001) and more CD161 + ( p < 0.05) Tregs compared to HD patients. This population has been described to be highly suppressive. HD had a deficiency in a Th17-like CD161 + effector Treg cluster (cluster iii., CCR6 + CCR4 + CXCR3 − CD39 + CD15s + ICOS − CCR7 − CD161 + ) ( p < 0.05). Discussion This is the first study presenting a deep Treg phenotype in HS patients. We confirmed that HS patients had more of a Th17-like CD161 + effector Treg from population III (CD4 + CD25 hi CD127 lo CD45RA − ) compared to non-sensitised patients on HD. The clinical relevance of this highly suppressive Tregs population remains to be determined in the context of transplantation.
{"title":"Highly sensitised individuals present a distinct Treg signature compared to unsensitised individuals on haemodialysis","authors":"C. Dudreuilh, S. Basu, O. Shaw, H. Burton, N. Mamode, F. Harris, T. Tree, P. Nedyalko, M. Terranova-Barberio, G. Lombardi, C. Scottà, A. Dorling","doi":"10.3389/frtra.2023.1165320","DOIUrl":"https://doi.org/10.3389/frtra.2023.1165320","url":null,"abstract":"Introduction Highly sensitised (HS) patients represent up to 30% of patients on the kidney transplant waiting list. When they are transplanted, they have a high risk of acute/chronic rejection and long-term allograft loss. Regulatory T cells (Tregs) (CD4 + CD25 hi CD127 lo ) are T cells involved in the suppression of immune alloresponses. A particular subset, called T follicular regulatory T cells (Tfr, CXCR5 + Bcl-6 + ), is involved in regulating interactions between T effectors and B cells within the germinal centre and can be found in peripheral blood. Therefore, we wanted to identify specific subsets of Tregs in the peripheral blood of HS individuals. Methods We recruited prospectively healthy volunteers (HV) ( n = 9), non-sensitised patients on haemodialysis (HD) ( n = 9) and HS individuals, all of whom were on haemodialysis ( n = 15). Results We compared the Treg phenotypes of HV, HD and HS. HS patients had more CD161 + Tregs ( p = 0.02) and more CD45RA − CCR7 − T effectors (Teffs) ( p = 0.04, memory Teffs able to home to the germinal centre) compared to HVs. HS patients had more Bcl-6 + Tregs ( p &lt; 0.05), fewer Th1-like Tregs, more Th2-like Tregs ( p &lt; 0.001) and more CD161 + ( p &lt; 0.05) Tregs compared to HD patients. This population has been described to be highly suppressive. HD had a deficiency in a Th17-like CD161 + effector Treg cluster (cluster iii., CCR6 + CCR4 + CXCR3 − CD39 + CD15s + ICOS − CCR7 − CD161 + ) ( p &lt; 0.05). Discussion This is the first study presenting a deep Treg phenotype in HS patients. We confirmed that HS patients had more of a Th17-like CD161 + effector Treg from population III (CD4 + CD25 hi CD127 lo CD45RA − ) compared to non-sensitised patients on HD. The clinical relevance of this highly suppressive Tregs population remains to be determined in the context of transplantation.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"964 ","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136068107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-30DOI: 10.3389/frtra.2023.1284740
Stephanie Ji, Hao Liu, Laura Pachella, Ryan D. Stephenson, Roman Groisberg, Sarah A. Weiss
Background Immune checkpoint inhibitors (ICI) are standard of care therapy for patients with cutaneous malignancies, the most frequently diagnosed cancers in solid organ transplant (SOT) recipients. The activity and rate of allograft rejection in SOT recipients with advanced skin cancers treated with ICI is understudied. Methods We conducted a retrospective analysis of SOT recipients with advanced melanoma, cutaneous squamous cell carcinoma (cSCC), and merkel cell carcinoma (MCC) who were treated with ICI. Unpublished cases from our institution and published cases from the literature were aggregated. Demographics, type of immunosuppressive therapy, type of ICI(s) administered, prior systemic therapies, tumor response to ICI, and evidence of organ rejection and/or failure were recorded. Objective response rates (ORR) and rates of graft rejection and failure are reported. Results Ninety patients were identified; four patients from our institution and 86 unique patients from a literature review. ORR to first-line ICI for the entire cohort was 41.1% (37/90). ORR by tumor type was 31% (18/58), 64.3% (18/28), and 25.0% (1/4) for melanoma, cSCC, and MCC, respectively. The rate of graft rejection was 37.8% (34/90) with 61.8% (21/34) of these cases progressing to graft failure. Number of immunosuppressive agents (0, 1, 2, or 3) was inversely associated with rate of graft failure. Conclusions In this retrospective analysis, ICIs demonstrate clinical activity in SOT recipients with cutaneous malignancies; however, the rate of graft rejection is high. Treatment plans should be individualized through thorough interdisciplinary discussion. Immunosuppressive modifications may be considered prior to starting treatment, but when feasible, enrollment on clinical trials is preferred.
{"title":"Use of immune checkpoint inhibitors in solid organ transplant recipients with advanced cutaneous malignancies","authors":"Stephanie Ji, Hao Liu, Laura Pachella, Ryan D. Stephenson, Roman Groisberg, Sarah A. Weiss","doi":"10.3389/frtra.2023.1284740","DOIUrl":"https://doi.org/10.3389/frtra.2023.1284740","url":null,"abstract":"Background Immune checkpoint inhibitors (ICI) are standard of care therapy for patients with cutaneous malignancies, the most frequently diagnosed cancers in solid organ transplant (SOT) recipients. The activity and rate of allograft rejection in SOT recipients with advanced skin cancers treated with ICI is understudied. Methods We conducted a retrospective analysis of SOT recipients with advanced melanoma, cutaneous squamous cell carcinoma (cSCC), and merkel cell carcinoma (MCC) who were treated with ICI. Unpublished cases from our institution and published cases from the literature were aggregated. Demographics, type of immunosuppressive therapy, type of ICI(s) administered, prior systemic therapies, tumor response to ICI, and evidence of organ rejection and/or failure were recorded. Objective response rates (ORR) and rates of graft rejection and failure are reported. Results Ninety patients were identified; four patients from our institution and 86 unique patients from a literature review. ORR to first-line ICI for the entire cohort was 41.1% (37/90). ORR by tumor type was 31% (18/58), 64.3% (18/28), and 25.0% (1/4) for melanoma, cSCC, and MCC, respectively. The rate of graft rejection was 37.8% (34/90) with 61.8% (21/34) of these cases progressing to graft failure. Number of immunosuppressive agents (0, 1, 2, or 3) was inversely associated with rate of graft failure. Conclusions In this retrospective analysis, ICIs demonstrate clinical activity in SOT recipients with cutaneous malignancies; however, the rate of graft rejection is high. Treatment plans should be individualized through thorough interdisciplinary discussion. Immunosuppressive modifications may be considered prior to starting treatment, but when feasible, enrollment on clinical trials is preferred.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"431 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136068061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-30DOI: 10.3389/frtra.2023.1178505
Eric Perakslis, Brian McCourt, Stuart Knechtle
The United States system of solid organ transplantation is overseen by the Organ Procurement Transplantation Network (OPTN). Recent announcements from the Health Resources and Services Administration (HRSA) indicate their clear intention to reform the system. We suggest that the original intention of the National Organ Transplant Act (NOTA) to require one entity to oversee transplantation is critical to integrate policy with the complex realities of organ procurement and transplantation practice. We suggest that a contemporary business platform model best captures the appropriate structure for coordinating organ transplantation, as the seamless exchange of organs between related groups is the essential function to facilitate. A business platform framework that includes public and private, academic and industry partners can best accomplish the important goal of equitable and efficient organ transplantation.
{"title":"Reimagining the United States organ procurement and transplant network","authors":"Eric Perakslis, Brian McCourt, Stuart Knechtle","doi":"10.3389/frtra.2023.1178505","DOIUrl":"https://doi.org/10.3389/frtra.2023.1178505","url":null,"abstract":"The United States system of solid organ transplantation is overseen by the Organ Procurement Transplantation Network (OPTN). Recent announcements from the Health Resources and Services Administration (HRSA) indicate their clear intention to reform the system. We suggest that the original intention of the National Organ Transplant Act (NOTA) to require one entity to oversee transplantation is critical to integrate policy with the complex realities of organ procurement and transplantation practice. We suggest that a contemporary business platform model best captures the appropriate structure for coordinating organ transplantation, as the seamless exchange of organs between related groups is the essential function to facilitate. A business platform framework that includes public and private, academic and industry partners can best accomplish the important goal of equitable and efficient organ transplantation.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136068268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-27DOI: 10.3389/frtra.2023.1264903
Wolfgang Arns, Aurélie Philippe, Vanessa Ditt, Ingeborg A. Hauser, Friedrich Thaiss, Claudia Sommerer, Barbara Suwelack, Duska Dragun, Jan Hillen, Christiane Schiedel, Anja Elsässer, Björn Nashan
Background Studies prospectively monitoring de novo donor-specific antibodies (dnDSAs) and their clinical impact are sparse. This substudy of ATHENA was initiated to evaluate the effect of everolimus (EVR) or mycophenolic acid (MPA) in combination with reduced calcineurin inhibitor (CNI, tacrolimus [TAC] or cyclosporine [CsA]) on the formation of human leukocyte antibodies (HLA), including dnDSA, and the impact on clinical outcomes in kidney transplant (KTx) recipients. Methods All eligible patients were randomized 1:1:1 to receive either EVR + TAC, EVR + CsA or MPA + TAC, with basiliximab induction plus steroids after transplantation up to Month 12. The incidence of dnDSA by treatment group and the association with clinical events were evaluated descriptively as an exploratory objective in the intent-to-treat (ITT) and per-protocol (PP) populations with at least one antibody assessment. Results Overall, none of the patients in the EVR + TAC group had either dnDSA or antibody mediated rejection (PP or ITT population) and only one patient with dnDSA in the TAC + MPA group had antibody mediated rejection. Conclusion The EVR regimen was comparable to MPA regimen with an extremely low incidence of dnDSA over 1 year of treatment.
{"title":"Everolimus plus reduced calcineurin inhibitor prevents de novo anti-HLA antibodies and humoral rejection in kidney transplant recipients: 12-month results from the ATHENA study","authors":"Wolfgang Arns, Aurélie Philippe, Vanessa Ditt, Ingeborg A. Hauser, Friedrich Thaiss, Claudia Sommerer, Barbara Suwelack, Duska Dragun, Jan Hillen, Christiane Schiedel, Anja Elsässer, Björn Nashan","doi":"10.3389/frtra.2023.1264903","DOIUrl":"https://doi.org/10.3389/frtra.2023.1264903","url":null,"abstract":"Background Studies prospectively monitoring de novo donor-specific antibodies (dnDSAs) and their clinical impact are sparse. This substudy of ATHENA was initiated to evaluate the effect of everolimus (EVR) or mycophenolic acid (MPA) in combination with reduced calcineurin inhibitor (CNI, tacrolimus [TAC] or cyclosporine [CsA]) on the formation of human leukocyte antibodies (HLA), including dnDSA, and the impact on clinical outcomes in kidney transplant (KTx) recipients. Methods All eligible patients were randomized 1:1:1 to receive either EVR + TAC, EVR + CsA or MPA + TAC, with basiliximab induction plus steroids after transplantation up to Month 12. The incidence of dnDSA by treatment group and the association with clinical events were evaluated descriptively as an exploratory objective in the intent-to-treat (ITT) and per-protocol (PP) populations with at least one antibody assessment. Results Overall, none of the patients in the EVR + TAC group had either dnDSA or antibody mediated rejection (PP or ITT population) and only one patient with dnDSA in the TAC + MPA group had antibody mediated rejection. Conclusion The EVR regimen was comparable to MPA regimen with an extremely low incidence of dnDSA over 1 year of treatment.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"13 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136317328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-27DOI: 10.3389/frtra.2023.1244093
So-Yoon Won, Sean M. Kinney, Michael V. Sefton
Islet transplantation is a promising treatment for type I diabetes (T1D). Despite the high loss of islets during transplantation, current islet transplant protocols continue to rely on portal vein infusion and intrahepatic engraftment. Because of the risk of portal vein thrombosis and the loss of islets to instant blood mediated inflammatory reaction (IBMIR), other transplantation sites like the subcutaneous space have been pursued for its large transplant volume, accessibility, and amenability for retrieval. To overcome the minimal vasculature of the subcutaneous space, prevascularization approaches or vascularizing biomaterials have been used to subcutaneously deliver islets into diabetic mice to return them to normoglycemia. Previous vascularization methods have relied on a 4 to 6 week prevascularization timeframe. Here we show that a vascularizing MAA-coated silicone tube can generate sufficient vasculature in 2 to 3 weeks to support a therapeutic dose of islets in mice. In order to fully harness the potential of this prevascularized site, we characterize the unique, subcutaneous immune response to allogeneic islets in the first 7 days following transplantation, a critical stage in successful engraftment. We identify neutrophils as a specific cellular target, a previously overlooked cell in the context of subcutaneous allogeneic islet transplantation. By perioperatively depleting neutrophils, we show that neutrophils are a key, innate immune cell target for successful early engraftment of allogeneic islets in a prevascularized subcutaneous site.
{"title":"Neutrophil depletion for early allogeneic islet survival in a methacrylic acid (MAA) copolymer-induced, vascularized subcutaneous space","authors":"So-Yoon Won, Sean M. Kinney, Michael V. Sefton","doi":"10.3389/frtra.2023.1244093","DOIUrl":"https://doi.org/10.3389/frtra.2023.1244093","url":null,"abstract":"Islet transplantation is a promising treatment for type I diabetes (T1D). Despite the high loss of islets during transplantation, current islet transplant protocols continue to rely on portal vein infusion and intrahepatic engraftment. Because of the risk of portal vein thrombosis and the loss of islets to instant blood mediated inflammatory reaction (IBMIR), other transplantation sites like the subcutaneous space have been pursued for its large transplant volume, accessibility, and amenability for retrieval. To overcome the minimal vasculature of the subcutaneous space, prevascularization approaches or vascularizing biomaterials have been used to subcutaneously deliver islets into diabetic mice to return them to normoglycemia. Previous vascularization methods have relied on a 4 to 6 week prevascularization timeframe. Here we show that a vascularizing MAA-coated silicone tube can generate sufficient vasculature in 2 to 3 weeks to support a therapeutic dose of islets in mice. In order to fully harness the potential of this prevascularized site, we characterize the unique, subcutaneous immune response to allogeneic islets in the first 7 days following transplantation, a critical stage in successful engraftment. We identify neutrophils as a specific cellular target, a previously overlooked cell in the context of subcutaneous allogeneic islet transplantation. By perioperatively depleting neutrophils, we show that neutrophils are a key, innate immune cell target for successful early engraftment of allogeneic islets in a prevascularized subcutaneous site.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"167 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136233962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-23DOI: 10.3389/frtra.2023.1269706
Yanis Berkane, Justine Hayau, Irina Filz von Reiterdank, Anil Kharga, Laura Charlès, Abele B. Mink van der Molen, J. Henk Coert, Nicolas Bertheuil, Mark A. Randolph, Curtis L. Cetrulo, Alban Longchamp, Alexandre G. Lellouch, Korkut Uygun
Ex vivo preservation of transplanted organs is undergoing spectacular advances. Machine perfusion is now used in common practice for abdominal and thoracic organ transportation and preservation, and early results are in favor of substantially improved outcomes. It is based on decreasing ischemia-reperfusion phenomena by providing physiological or sub-physiological conditions until transplantation. Alternatively, supercooling techniques involving static preservation at negative temperatures while avoiding ice formation have shown encouraging results in solid organs. Here, the rationale is to decrease the organ's metabolism and need for oxygen and nutrients, allowing for extended preservation durations. The aim of this work is to review all advances of supercooling in transplantation, browsing the literature for each organ. A specific objective was also to study the initial evidence, the prospects, and potential applications of supercooling preservation in Vascularized Composite Allotransplantation (VCA). This complex entity needs a substantial effort to improve long-term outcomes, marked by chronic rejection. Improving preservation techniques is critical to ensure the favorable evolution of VCAs, and supercooling techniques could greatly participate in these advances.
{"title":"Supercooling: a promising technique for prolonged preservation in solid organ transplantation, and early perspectives in vascularized composite allografts","authors":"Yanis Berkane, Justine Hayau, Irina Filz von Reiterdank, Anil Kharga, Laura Charlès, Abele B. Mink van der Molen, J. Henk Coert, Nicolas Bertheuil, Mark A. Randolph, Curtis L. Cetrulo, Alban Longchamp, Alexandre G. Lellouch, Korkut Uygun","doi":"10.3389/frtra.2023.1269706","DOIUrl":"https://doi.org/10.3389/frtra.2023.1269706","url":null,"abstract":"Ex vivo preservation of transplanted organs is undergoing spectacular advances. Machine perfusion is now used in common practice for abdominal and thoracic organ transportation and preservation, and early results are in favor of substantially improved outcomes. It is based on decreasing ischemia-reperfusion phenomena by providing physiological or sub-physiological conditions until transplantation. Alternatively, supercooling techniques involving static preservation at negative temperatures while avoiding ice formation have shown encouraging results in solid organs. Here, the rationale is to decrease the organ's metabolism and need for oxygen and nutrients, allowing for extended preservation durations. The aim of this work is to review all advances of supercooling in transplantation, browsing the literature for each organ. A specific objective was also to study the initial evidence, the prospects, and potential applications of supercooling preservation in Vascularized Composite Allotransplantation (VCA). This complex entity needs a substantial effort to improve long-term outcomes, marked by chronic rejection. Improving preservation techniques is critical to ensure the favorable evolution of VCAs, and supercooling techniques could greatly participate in these advances.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"333 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135368319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-10-16DOI: 10.3389/frtra.2023.1279940
Arlisson Macedo Rodrigues, Mariana Tavares Tanno, Mariana Moraes Contti, Hong Si Nga, Mariana Farina Valiatti, Silvana Daher Costa, Tainá Veras de Sandes-Freitas, Ronaldo de Matos Esmeraldo, Camila Marinho Assunção, Juliana Bastos Campos Tassi, Gustavo Fernandes Ferreira, Claudia Rosso Felipe, Jose Osmar Medina Pestana, Helio Tedesco Silva, Luis Gustavo Modelli de Andrade
Introduction The combination of tacrolimus/mTORi compared to tacrolimus/mycophenolate (MMF) was shown to be safe in the TRANSFORM trial. For donors with a high KDPI (Kidney Donor Profile Index), however, there are no data to support the effectiveness of this regimen. The main objective of this study was to explore the influence of the KDPI on 12-month renal function (eGFR) in patients receiving mTORi or MMF. Methods Multicenter cohort study of four Brazilian services that use the tacrolimus with mTORi as a protocol. Data from 2008 to 2018 of the tacrolimus/mycophenolate (MMF) and tacrolimus/mTORi (mTORi) regimens in renal transplant recipients over 18 years old were collected. For better homogeneity, the propensity score was used. Afterward, the method used for group selection (“match”) was the K-nearest neighbor (KNN) method. New analyses were performed on this new balanced sample, and two different subsamples were constituted based on the median KDPI. Results The global analysis ( n = 870) showed that the major determinant of worse kidney function was high KDPI. Afterward, the three strata were analyzed. In the first stratum (KDPI up to 50), 242 patients were evaluated, with 121 in each group. The eGFR was 64 ml/min/1.73 m2 in the mTORi group compared to 63 in the MMF group, p = 0.4, and when imputed eGFR was evaluated, 61 in the mTORi and 53 in the MMF, p = 0.065. In the second stratum (KDPI from 50 to 85), 282 patients were evaluated, with 141 in each group. eGFR was 46 ml/min/1.73 m2 in mTORi compared to 48 in MMF, p = 0.4, and when imputed eGFR was evaluated, 40 mTORi and 41 MMF, p = 0.8. In the last stratum (KDPI higher than 85) with n = 126 and 63 cases per group, eGFR was 36 ml/min/1.73 m2 in mTORi compared to 39 in MMF, p = 0.2, and when imputed eGFR was evaluated, 30 mTORi and 34 MMF, p = 0.2. Discussion The regimen using mTOR inhibitor is an effective and safe regimen when compared to the standard regimen. In addition, the scheme seems to offer additional protection against infections and may be an important ally in cases of high risk for these pathologies.
在TRANSFORM试验中，与他克莫司/霉酚酸酯(MMF)相比，他克莫司/mTORi联合用药是安全的。然而，对于高KDPI(肾脏供者概况指数)的供者，没有数据支持该方案的有效性。本研究的主要目的是探讨KDPI对mTORi或MMF患者12个月肾功能(eGFR)的影响。方法对巴西4家使用他克莫司联合mTORi治疗方案的医院进行多中心队列研究。收集了2008年至2018年18岁以上肾移植受者他克莫司/霉酚酸酯(MMF)和他克莫司/mTORi (mTORi)方案的数据。为了更好的同质性，使用倾向评分。之后，用于分组选择(“匹配”)的方法是k最近邻(KNN)方法。对这个新的平衡样本进行了新的分析，并根据中位数KDPI构成了两个不同的子样本。结果全球分析(n = 870)显示肾功能恶化的主要决定因素是高KDPI。随后，对三层进行了分析。在第一阶段(KDPI为50)，242例患者接受评估，每组121例。mTORi组的eGFR为64 ml/min/1.73 m2，而MMF组为63 ml/min/1.73 m2, p = 0.4，当计算eGFR时，mTORi组为61 ml/min, MMF组为53 ml/min, p = 0.065。在第二阶段(KDPI从50到85)，282例患者被评估，每组141例。mTORi组eGFR为46 ml/min/1.73 m2，而MMF组为48 ml/min/1.73 m2, p = 0.4，当计算eGFR时，mTORi组为40 ml/min, MMF组为41 ml/min, p = 0.8。在最后一层(KDPI高于85)，n = 126，每组63例，mTORi的eGFR为36 ml/min/1.73 m2，而MMF为39 ml/min/1.73 m2, p = 0.2，当估算估算eGFR时，mTORi为30 ml/min, MMF为34,p = 0.2。与标准方案相比，使用mTOR抑制剂的方案是一种有效且安全的方案。此外，该方案似乎提供了额外的预防感染的保护，并可能是这些疾病高风险病例的重要盟友。
{"title":"Renal function at 12 months of kidney transplantation comparing tacrolimus and mycophenolate with tacrolimus and mTORi in donors with different KDPI ranges. A multicenter cohort study using propensity scoring","authors":"Arlisson Macedo Rodrigues, Mariana Tavares Tanno, Mariana Moraes Contti, Hong Si Nga, Mariana Farina Valiatti, Silvana Daher Costa, Tainá Veras de Sandes-Freitas, Ronaldo de Matos Esmeraldo, Camila Marinho Assunção, Juliana Bastos Campos Tassi, Gustavo Fernandes Ferreira, Claudia Rosso Felipe, Jose Osmar Medina Pestana, Helio Tedesco Silva, Luis Gustavo Modelli de Andrade","doi":"10.3389/frtra.2023.1279940","DOIUrl":"https://doi.org/10.3389/frtra.2023.1279940","url":null,"abstract":"Introduction The combination of tacrolimus/mTORi compared to tacrolimus/mycophenolate (MMF) was shown to be safe in the TRANSFORM trial. For donors with a high KDPI (Kidney Donor Profile Index), however, there are no data to support the effectiveness of this regimen. The main objective of this study was to explore the influence of the KDPI on 12-month renal function (eGFR) in patients receiving mTORi or MMF. Methods Multicenter cohort study of four Brazilian services that use the tacrolimus with mTORi as a protocol. Data from 2008 to 2018 of the tacrolimus/mycophenolate (MMF) and tacrolimus/mTORi (mTORi) regimens in renal transplant recipients over 18 years old were collected. For better homogeneity, the propensity score was used. Afterward, the method used for group selection (“match”) was the K-nearest neighbor (KNN) method. New analyses were performed on this new balanced sample, and two different subsamples were constituted based on the median KDPI. Results The global analysis ( n = 870) showed that the major determinant of worse kidney function was high KDPI. Afterward, the three strata were analyzed. In the first stratum (KDPI up to 50), 242 patients were evaluated, with 121 in each group. The eGFR was 64 ml/min/1.73 m2 in the mTORi group compared to 63 in the MMF group, p = 0.4, and when imputed eGFR was evaluated, 61 in the mTORi and 53 in the MMF, p = 0.065. In the second stratum (KDPI from 50 to 85), 282 patients were evaluated, with 141 in each group. eGFR was 46 ml/min/1.73 m2 in mTORi compared to 48 in MMF, p = 0.4, and when imputed eGFR was evaluated, 40 mTORi and 41 MMF, p = 0.8. In the last stratum (KDPI higher than 85) with n = 126 and 63 cases per group, eGFR was 36 ml/min/1.73 m2 in mTORi compared to 39 in MMF, p = 0.2, and when imputed eGFR was evaluated, 30 mTORi and 34 MMF, p = 0.2. Discussion The regimen using mTOR inhibitor is an effective and safe regimen when compared to the standard regimen. In addition, the scheme seems to offer additional protection against infections and may be an important ally in cases of high risk for these pathologies.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136113464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-29DOI: 10.3389/frtra.2023.1248284
William Brandon, Colin Dunn, Srinivas Bollineni, John Joerns, Adrian Lawrence, Manish Mohanka, Irina Timofte, Fernando Torres, Vaidehi Kaza
The formation of antibodies against donor human leukocyte antigens poses a challenging problem both for donor selection as well as postoperative graft function in lung transplantation. These donor-specific antibodies limit the pool of potential donor organs and are associated with episodes of antibody-mediated rejection, chronic lung allograft dysfunction, and increased mortality. Optimal management strategies for clearance of DSAs are poorly defined and vary greatly by institution; most of the data supporting any particular strategy is limited to small-scale retrospective cohort studies. A typical approach to antibody depletion may involve the use of high-dose steroids, plasma exchange, intravenous immunoglobulin, and possibly other immunomodulators or small-molecule therapies. This review seeks to define the current understanding of the significance of DSAs in lung transplantation and outline the literature supporting strategies for their management.
{"title":"Management of donor-specific antibodies in lung transplantation","authors":"William Brandon, Colin Dunn, Srinivas Bollineni, John Joerns, Adrian Lawrence, Manish Mohanka, Irina Timofte, Fernando Torres, Vaidehi Kaza","doi":"10.3389/frtra.2023.1248284","DOIUrl":"https://doi.org/10.3389/frtra.2023.1248284","url":null,"abstract":"The formation of antibodies against donor human leukocyte antigens poses a challenging problem both for donor selection as well as postoperative graft function in lung transplantation. These donor-specific antibodies limit the pool of potential donor organs and are associated with episodes of antibody-mediated rejection, chronic lung allograft dysfunction, and increased mortality. Optimal management strategies for clearance of DSAs are poorly defined and vary greatly by institution; most of the data supporting any particular strategy is limited to small-scale retrospective cohort studies. A typical approach to antibody depletion may involve the use of high-dose steroids, plasma exchange, intravenous immunoglobulin, and possibly other immunomodulators or small-molecule therapies. This review seeks to define the current understanding of the significance of DSAs in lung transplantation and outline the literature supporting strategies for their management.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135245972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-29DOI: 10.3389/frtra.2023.1130086
Davinia Beaver, Ioannis Jason Limnios
Stem cell therapies can potentially treat various retinal degenerative diseases, including age-related macular degeneration (AMD) and inherited retinal diseases like retinitis pigmentosa. For these diseases, transplanted cells may include stem cell-derived retinal pigmented epithelial (RPE) cells, photoreceptors, or a combination of both. Although stem cell-derived RPE cells have progressed to human clinical trials, therapies using photoreceptors and other retinal cell types are lagging. In this review, we discuss the potential use of human pluripotent stem cell (hPSC)-derived photoreceptors for the treatment of retinal degeneration and highlight the progress and challenges for their efficient production and clinical application in regenerative medicine.
{"title":"A treatment within sight: challenges in the development of stem cell-derived photoreceptor therapies for retinal degenerative diseases","authors":"Davinia Beaver, Ioannis Jason Limnios","doi":"10.3389/frtra.2023.1130086","DOIUrl":"https://doi.org/10.3389/frtra.2023.1130086","url":null,"abstract":"Stem cell therapies can potentially treat various retinal degenerative diseases, including age-related macular degeneration (AMD) and inherited retinal diseases like retinitis pigmentosa. For these diseases, transplanted cells may include stem cell-derived retinal pigmented epithelial (RPE) cells, photoreceptors, or a combination of both. Although stem cell-derived RPE cells have progressed to human clinical trials, therapies using photoreceptors and other retinal cell types are lagging. In this review, we discuss the potential use of human pluripotent stem cell (hPSC)-derived photoreceptors for the treatment of retinal degeneration and highlight the progress and challenges for their efficient production and clinical application in regenerative medicine.","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"54 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135199691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Time for transplant care professionals to face recipients' fear of graft rejection—an opinion paper","authors":"Anna Forsberg, Nichon Jansen, David Paredes, Hannah Maple","doi":"10.3389/frtra.2023.1277053","DOIUrl":"https://doi.org/10.3389/frtra.2023.1277053","url":null,"abstract":"OPINION article Front. Transplant., 29 September 2023Sec. Transplantation Immunology Volume 2 - 2023 | https://doi.org/10.3389/frtra.2023.1277053","PeriodicalId":483606,"journal":{"name":"Frontiers in Transplantation","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135245794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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