{"title":"免疫抑制药物浓度对肾移植受者微血管炎症、供体特异性抗体阴性和c4d阴性状态的影响","authors":"Yoichi Kakuta, Yoko Maegawa-Higa, Soichi Matsumura, Shota Fukae, Ryo Tanaka, Hiroaki Yonishi, Shigeaki Nakazawa, Tomoko Namba-Hamano, Yoshitaka Isaka, Norio Nonomura","doi":"10.1111/ctr.70112","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Introduction</h3>\n \n <p>This study investigated the impact of immunosuppressive drug concentrations on microvascular inflammation (MVI) in kidney transplant recipients with negative donor-specific antibodies (DSA) against human leukocyte antigen (HLA) and negative C4d deposition in peritubular capillaries.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We analyzed data from 268 living kidney transplant recipients at the Department of Urology, University of Osaka, Japan. Patients received immunosuppressive therapy comprising extended-release tacrolimus, mycophenolate mofetil (MMF), and/or everolimus, with or without steroids. Graft biopsies were routinely performed at 3, 12, 36 and 60 months post-surgery.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>No significant differences were observed between the MVI+DSA-C4d- and MVI-DSAC4d groups regarding graft survival rates (95.5% vs. 96.6%, <i>p</i> = 0.772) or patient survival rates (95.7% vs. 95.9%, <i>p</i> = 0.735). Lower tacrolimus and everolimus concentrations were significantly associated with an increased risk of MVI+DSA-C4d- (tacrolimus: OR, 0.169; 95% CI, 0.055–0.515; <i>p</i> = 0.002; everolimus: OR, 0.386; 95% CI, 0.171–0.874; <i>p</i> = 0.022). In contrast, MPA concentration was not significantly associated with MVI+DSA-C4d- (OR, 0.994; 95% CI, 0.554–1.780; <i>p</i> = 0.984). Steroid discontinuation did not significantly impact the risk of MVI+DSA-C4d- (OR, 1.980; 95% CI, 0.318–12.000; <i>p</i> = 0.470).</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Lower trough levels of tacrolimus and everolimus correlated with a higher incidence of antibody-independent MVI, supporting the need for tailored immunosuppressive regimens in kidney transplantation.</p>\n </section>\n </div>","PeriodicalId":10467,"journal":{"name":"Clinical Transplantation","volume":"39 2","pages":""},"PeriodicalIF":1.9000,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ctr.70112","citationCount":"0","resultStr":"{\"title\":\"Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor-Specific Antibodies, and C4d-Negative Status in Kidney Transplant Recipients\",\"authors\":\"Yoichi Kakuta, Yoko Maegawa-Higa, Soichi Matsumura, Shota Fukae, Ryo Tanaka, Hiroaki Yonishi, Shigeaki Nakazawa, Tomoko Namba-Hamano, Yoshitaka Isaka, Norio Nonomura\",\"doi\":\"10.1111/ctr.70112\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Introduction</h3>\\n \\n <p>This study investigated the impact of immunosuppressive drug concentrations on microvascular inflammation (MVI) in kidney transplant recipients with negative donor-specific antibodies (DSA) against human leukocyte antigen (HLA) and negative C4d deposition in peritubular capillaries.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We analyzed data from 268 living kidney transplant recipients at the Department of Urology, University of Osaka, Japan. Patients received immunosuppressive therapy comprising extended-release tacrolimus, mycophenolate mofetil (MMF), and/or everolimus, with or without steroids. Graft biopsies were routinely performed at 3, 12, 36 and 60 months post-surgery.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>No significant differences were observed between the MVI+DSA-C4d- and MVI-DSAC4d groups regarding graft survival rates (95.5% vs. 96.6%, <i>p</i> = 0.772) or patient survival rates (95.7% vs. 95.9%, <i>p</i> = 0.735). Lower tacrolimus and everolimus concentrations were significantly associated with an increased risk of MVI+DSA-C4d- (tacrolimus: OR, 0.169; 95% CI, 0.055–0.515; <i>p</i> = 0.002; everolimus: OR, 0.386; 95% CI, 0.171–0.874; <i>p</i> = 0.022). In contrast, MPA concentration was not significantly associated with MVI+DSA-C4d- (OR, 0.994; 95% CI, 0.554–1.780; <i>p</i> = 0.984). 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引用次数: 0
摘要
本研究探讨了免疫抑制药物浓度对抗人白细胞抗原（HLA）供体特异性抗体（DSA）阴性和肾小管周围毛细血管C4d沉积阴性肾移植受者微血管炎症（MVI）的影响。方法：我们分析了日本大阪大学泌尿外科268例活体肾移植受者的资料。患者接受免疫抑制治疗，包括缓释他克莫司、霉酚酸酯（MMF）和/或依维莫司，伴或不伴类固醇。术后3、12、36、60个月常规行移植物活检。结果MVI+DSA-C4d组和MVI- dsac4d组在移植物存活率（95.5% vs. 96.6%, p = 0.772）和患者生存率（95.7% vs. 95.9%, p = 0.735）方面无显著差异。较低的他克莫司和依维莫司浓度与MVI+DSA-C4d-的风险增加显著相关(他克莫司：OR， 0.169；95% ci, 0.055-0.515；p = 0.002；依维莫司：OR 0.386；95% ci, 0.171-0.874；p = 0.022)。MPA浓度与MVI+DSA-C4d-无显著相关性(OR, 0.994；95% ci, 0.554-1.780；p = 0.984)。停用类固醇对MVI+DSA-C4d-的风险无显著影响(OR, 1.980；95% ci, 0.318-12.000；p = 0.470)。结论他克莫司和依维莫司较低的谷值与较高的抗体非依赖性MVI发生率相关，支持在肾移植中定制免疫抑制方案的必要性。
Impact of Immunosuppressive Drug Concentrations on Microvascular Inflammation, Negative Donor-Specific Antibodies, and C4d-Negative Status in Kidney Transplant Recipients
Introduction
This study investigated the impact of immunosuppressive drug concentrations on microvascular inflammation (MVI) in kidney transplant recipients with negative donor-specific antibodies (DSA) against human leukocyte antigen (HLA) and negative C4d deposition in peritubular capillaries.
Methods
We analyzed data from 268 living kidney transplant recipients at the Department of Urology, University of Osaka, Japan. Patients received immunosuppressive therapy comprising extended-release tacrolimus, mycophenolate mofetil (MMF), and/or everolimus, with or without steroids. Graft biopsies were routinely performed at 3, 12, 36 and 60 months post-surgery.
Results
No significant differences were observed between the MVI+DSA-C4d- and MVI-DSAC4d groups regarding graft survival rates (95.5% vs. 96.6%, p = 0.772) or patient survival rates (95.7% vs. 95.9%, p = 0.735). Lower tacrolimus and everolimus concentrations were significantly associated with an increased risk of MVI+DSA-C4d- (tacrolimus: OR, 0.169; 95% CI, 0.055–0.515; p = 0.002; everolimus: OR, 0.386; 95% CI, 0.171–0.874; p = 0.022). In contrast, MPA concentration was not significantly associated with MVI+DSA-C4d- (OR, 0.994; 95% CI, 0.554–1.780; p = 0.984). Steroid discontinuation did not significantly impact the risk of MVI+DSA-C4d- (OR, 1.980; 95% CI, 0.318–12.000; p = 0.470).
Conclusion
Lower trough levels of tacrolimus and everolimus correlated with a higher incidence of antibody-independent MVI, supporting the need for tailored immunosuppressive regimens in kidney transplantation.
期刊介绍：
Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored.
Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include:
Immunology and immunosuppression;
Patient preparation;
Social, ethical, and psychological issues;
Complications, short- and long-term results;
Artificial organs;
Donation and preservation of organ and tissue;
Translational studies;
Advances in tissue typing;
Updates on transplant pathology;.
Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries.
Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.
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