Megan Henderson, Linda Awdishu, Gerald P Morris, Kassandra Fabbri, Mita Shah, Adnan Khan, Janice Kerr
{"title":"他克莫司水平的细微变化对肾移植早期供体特异性抗体有影响。","authors":"Megan Henderson, Linda Awdishu, Gerald P Morris, Kassandra Fabbri, Mita Shah, Adnan Khan, Janice Kerr","doi":"10.1177/15269248231212923","DOIUrl":null,"url":null,"abstract":"<p><p><b>Introduction:</b> The impact of each immunosuppressive agent on de novo donor-specific antibodies in kidney transplant recipients varies among extant literature. <b>Project aims:</b> Patterns in immunosuppression and the effects on incidence of de novo donor-specific antibodies were evaluated. <b>Design:</b> Adult kidney transplant recipients from 2017 to 2019 without preformed antibodies were sampled. Allograft function, de novo donor-specific antibodies, tacrolimus concentrations, duration of goal-dose antiproliferatives, and steroid doses were recorded. Outcomes included incidence of de novo donor-specific antibodies, and their relation to tacrolimus concentrations, time at goal-dose antiproliferatives, and steroid doses. <b>Results:</b> Recipients (N = 153) were followed for 1 year; all were crossmatch negative and received rabbit antithymocyte globulin induction. Sixteen (10%) recipients developed de novo donor-specific antibodies in a median of 31 days [interquartile range, IQR: 12-67 days], most were Class II antibodies (87.5%). Incidence of de novo donor-specific antibodies did not differ based on induction dosing. Tacrolimus levels in the first month were lower for patients with de novo donor-specific antibodies (8.8 ng/mL vs 10.4 ng/mL, <i>P</i> < .01). There was no difference in time on goal antiproliferative doses, but higher steroid doses (0.4 vs 0.3 mg/kg/d; <i>P</i> = .02) were noted in patients with antibodies. Steroid dosing was likely impacted by baseline risk factors. <b>Conclusion:</b> A significant association was found between lower tacrolimus concentrations early post-transplant and incidence of de novo donor-specific antibodies. This highlighted the importance of clinician attention to subtle changes in tacrolimus and the impact it can have on antibody risk in the early post-transplant period.</p>","PeriodicalId":0,"journal":{"name":"","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Subtle Changes in Tacrolimus Levels Have an Impact on Early Donor-Specific Antibodies in Kidney Transplantation.\",\"authors\":\"Megan Henderson, Linda Awdishu, Gerald P Morris, Kassandra Fabbri, Mita Shah, Adnan Khan, Janice Kerr\",\"doi\":\"10.1177/15269248231212923\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Introduction:</b> The impact of each immunosuppressive agent on de novo donor-specific antibodies in kidney transplant recipients varies among extant literature. <b>Project aims:</b> Patterns in immunosuppression and the effects on incidence of de novo donor-specific antibodies were evaluated. <b>Design:</b> Adult kidney transplant recipients from 2017 to 2019 without preformed antibodies were sampled. Allograft function, de novo donor-specific antibodies, tacrolimus concentrations, duration of goal-dose antiproliferatives, and steroid doses were recorded. Outcomes included incidence of de novo donor-specific antibodies, and their relation to tacrolimus concentrations, time at goal-dose antiproliferatives, and steroid doses. <b>Results:</b> Recipients (N = 153) were followed for 1 year; all were crossmatch negative and received rabbit antithymocyte globulin induction. Sixteen (10%) recipients developed de novo donor-specific antibodies in a median of 31 days [interquartile range, IQR: 12-67 days], most were Class II antibodies (87.5%). Incidence of de novo donor-specific antibodies did not differ based on induction dosing. Tacrolimus levels in the first month were lower for patients with de novo donor-specific antibodies (8.8 ng/mL vs 10.4 ng/mL, <i>P</i> < .01). There was no difference in time on goal antiproliferative doses, but higher steroid doses (0.4 vs 0.3 mg/kg/d; <i>P</i> = .02) were noted in patients with antibodies. Steroid dosing was likely impacted by baseline risk factors. <b>Conclusion:</b> A significant association was found between lower tacrolimus concentrations early post-transplant and incidence of de novo donor-specific antibodies. This highlighted the importance of clinician attention to subtle changes in tacrolimus and the impact it can have on antibody risk in the early post-transplant period.</p>\",\"PeriodicalId\":0,\"journal\":{\"name\":\"\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/15269248231212923\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/11/9 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/15269248231212923","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/11/9 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
引言:每种免疫抑制剂对肾移植受者新的供体特异性抗体的影响因现有文献而异。项目目的:评估免疫抑制模式和对新供体特异性抗体发生率的影响。设计:对2017年至2019年没有预先形成抗体的成年肾移植受者进行采样。记录同种异体移植物功能、新供体特异性抗体、他克莫司浓度、目标剂量抗增殖剂的持续时间和类固醇剂量。结果包括新的供体特异性抗体的发生率,以及它们与他克莫司浓度、目标剂量抗增殖剂的时间和类固醇剂量的关系。结果:受试者(N=153)随访1年;均为交叉配型阴性,接受兔抗胸腺细胞球蛋白诱导。16(10%)受试者在中位31天内产生了新的供体特异性抗体[四分位间距,IQR:12-67天],大多数是II类抗体(87.5%)。新的供体特异性抗体的发生率根据诱导给药没有差异。具有新供体特异性抗体的患者在第一个月的他克莫司水平较低(8.8 ng/mL vs 10.4 ng/mL,P<0.01)。在达到目标抗增殖剂量的时间上没有差异,但在具有抗体的患者中观察到较高的类固醇剂量(0.4 vs 0.3 mg/kg/d;P=.02)。类固醇给药可能受到基线风险因素的影响。结论:移植后早期较低的他克莫司浓度与新的供体特异性抗体的发生率之间存在显著相关性。这突出了临床医生关注他克莫司细微变化的重要性,以及它对移植后早期抗体风险的影响。
Subtle Changes in Tacrolimus Levels Have an Impact on Early Donor-Specific Antibodies in Kidney Transplantation.
Introduction: The impact of each immunosuppressive agent on de novo donor-specific antibodies in kidney transplant recipients varies among extant literature. Project aims: Patterns in immunosuppression and the effects on incidence of de novo donor-specific antibodies were evaluated. Design: Adult kidney transplant recipients from 2017 to 2019 without preformed antibodies were sampled. Allograft function, de novo donor-specific antibodies, tacrolimus concentrations, duration of goal-dose antiproliferatives, and steroid doses were recorded. Outcomes included incidence of de novo donor-specific antibodies, and their relation to tacrolimus concentrations, time at goal-dose antiproliferatives, and steroid doses. Results: Recipients (N = 153) were followed for 1 year; all were crossmatch negative and received rabbit antithymocyte globulin induction. Sixteen (10%) recipients developed de novo donor-specific antibodies in a median of 31 days [interquartile range, IQR: 12-67 days], most were Class II antibodies (87.5%). Incidence of de novo donor-specific antibodies did not differ based on induction dosing. Tacrolimus levels in the first month were lower for patients with de novo donor-specific antibodies (8.8 ng/mL vs 10.4 ng/mL, P < .01). There was no difference in time on goal antiproliferative doses, but higher steroid doses (0.4 vs 0.3 mg/kg/d; P = .02) were noted in patients with antibodies. Steroid dosing was likely impacted by baseline risk factors. Conclusion: A significant association was found between lower tacrolimus concentrations early post-transplant and incidence of de novo donor-specific antibodies. This highlighted the importance of clinician attention to subtle changes in tacrolimus and the impact it can have on antibody risk in the early post-transplant period.