{"title":"移植前他克莫司波动预测肾移植患者BK病毒感染风险","authors":"Hisashi Sakurai, Teppei Okamoto, Anna Yonemaya, Fumiya Yonemaya, Tomoko Hamaya, Hirotake Kodama, Naoki Fujita, Hayato Yamamoto, Kazuyuki Mori, Takeshi Fujita, Atushi Imai, Reiichi Murakami, Hirofumi Tomita, Shingo Hatakeyama, Chikara Ohyama","doi":"10.1007/s10157-025-02649-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>BK virus (BKV) infection is a significant complication in kidney transplant recipients, potentially leading to graft loss. The relationship between pre-transplant tacrolimus (TAC) pharmacokinetics and BKV infection risk remains unclear. This study aimed to investigate whether pre-transplant TAC blood concentration fluctuations are associated with BKV infection risk.</p><p><strong>Methods: </strong>We conducted a retrospective study of 135 living donor kidney transplant recipients at Hirosaki University between 2006 and March 2024. Patients were divided into BKV-infected (BKV) and non-infected (non-BKV) groups. TAC blood concentrations were measured at 4 points, including 0 h (2 h before TAC administration), 4, 6, and 12 h on the day before transplantation. Changes in TAC concentration from baseline (0 h) were calculated for each time point. The concentration/dose (C0/D) ratio was used as an indicator of TAC metabolism rate.</p><p><strong>Results: </strong>During a median follow-up of 54 months, 29 recipients developed BKV infection. The BKV group had significantly older donors and showed a significantly larger decrease in TAC concentration at 12 h compared to the non-BKV group (-1.5 vs. 0 ng/mL, P = 0.008). There was no significant difference in pre-transplant C0/D ratios between the two groups. A decrease of ≥ 1.5 ng/mL at 12 h was identified as a significant risk factor for BKV infection (hazard ratio: 2.44, 95% confidence interval: 1.11-5.32, P = 0.026) in a propensity score-based inverse probability of treatment weighting multivariate Cox proportional hazards analysis.</p><p><strong>Conclusion: </strong>Pre-transplant TAC blood concentration fluctuations, particularly a large decrease at 12 h from baseline, may be associated with increased BKV infection risk.</p>","PeriodicalId":10349,"journal":{"name":"Clinical and Experimental Nephrology","volume":" ","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pre-transplant tacrolimus fluctuations predict BK virus infection risk in kidney transplants.\",\"authors\":\"Hisashi Sakurai, Teppei Okamoto, Anna Yonemaya, Fumiya Yonemaya, Tomoko Hamaya, Hirotake Kodama, Naoki Fujita, Hayato Yamamoto, Kazuyuki Mori, Takeshi Fujita, Atushi Imai, Reiichi Murakami, Hirofumi Tomita, Shingo Hatakeyama, Chikara Ohyama\",\"doi\":\"10.1007/s10157-025-02649-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>BK virus (BKV) infection is a significant complication in kidney transplant recipients, potentially leading to graft loss. The relationship between pre-transplant tacrolimus (TAC) pharmacokinetics and BKV infection risk remains unclear. This study aimed to investigate whether pre-transplant TAC blood concentration fluctuations are associated with BKV infection risk.</p><p><strong>Methods: </strong>We conducted a retrospective study of 135 living donor kidney transplant recipients at Hirosaki University between 2006 and March 2024. Patients were divided into BKV-infected (BKV) and non-infected (non-BKV) groups. TAC blood concentrations were measured at 4 points, including 0 h (2 h before TAC administration), 4, 6, and 12 h on the day before transplantation. Changes in TAC concentration from baseline (0 h) were calculated for each time point. The concentration/dose (C0/D) ratio was used as an indicator of TAC metabolism rate.</p><p><strong>Results: </strong>During a median follow-up of 54 months, 29 recipients developed BKV infection. The BKV group had significantly older donors and showed a significantly larger decrease in TAC concentration at 12 h compared to the non-BKV group (-1.5 vs. 0 ng/mL, P = 0.008). There was no significant difference in pre-transplant C0/D ratios between the two groups. A decrease of ≥ 1.5 ng/mL at 12 h was identified as a significant risk factor for BKV infection (hazard ratio: 2.44, 95% confidence interval: 1.11-5.32, P = 0.026) in a propensity score-based inverse probability of treatment weighting multivariate Cox proportional hazards analysis.</p><p><strong>Conclusion: </strong>Pre-transplant TAC blood concentration fluctuations, particularly a large decrease at 12 h from baseline, may be associated with increased BKV infection risk.</p>\",\"PeriodicalId\":10349,\"journal\":{\"name\":\"Clinical and Experimental Nephrology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.2000,\"publicationDate\":\"2025-03-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Experimental Nephrology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10157-025-02649-0\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Experimental Nephrology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10157-025-02649-0","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景：BKV病毒（BKV）感染是肾移植受者的重要并发症，可能导致移植物丢失。移植前他克莫司（TAC）药代动力学与BKV感染风险的关系尚不清楚。本研究旨在探讨移植前TAC血浓度波动是否与BKV感染风险相关。方法：我们对2006年至2024年3月期间hiroaki大学135名活体肾移植受者进行了回顾性研究。患者分为BKV感染组（BKV）和非BKV感染组（non-BKV）。在移植前一天0小时（给药前2小时）、4小时、6小时和12小时4点测定TAC血药浓度。计算每个时间点与基线（0 h）相比TAC浓度的变化。以浓度/剂量（C0/D）比作为TAC代谢率的指标。结果：在中位随访54个月期间，29名受者发生BKV感染。与非BKV组相比，BKV组的供者明显更老，并且在12 h时TAC浓度的下降幅度更大（-1.5 vs. 0 ng/mL, P = 0.008）。两组移植前C0/D比值无显著差异。在基于倾向评分的治疗加权多因素Cox比例风险分析中，12 h时降低≥1.5 ng/mL被确定为BKV感染的重要危险因素（风险比：2.44,95%置信区间：1.11-5.32,P = 0.026）。结论：移植前TAC血浓度波动，特别是在12小时较基线大幅下降，可能与BKV感染风险增加有关。
Pre-transplant tacrolimus fluctuations predict BK virus infection risk in kidney transplants.
Background: BK virus (BKV) infection is a significant complication in kidney transplant recipients, potentially leading to graft loss. The relationship between pre-transplant tacrolimus (TAC) pharmacokinetics and BKV infection risk remains unclear. This study aimed to investigate whether pre-transplant TAC blood concentration fluctuations are associated with BKV infection risk.
Methods: We conducted a retrospective study of 135 living donor kidney transplant recipients at Hirosaki University between 2006 and March 2024. Patients were divided into BKV-infected (BKV) and non-infected (non-BKV) groups. TAC blood concentrations were measured at 4 points, including 0 h (2 h before TAC administration), 4, 6, and 12 h on the day before transplantation. Changes in TAC concentration from baseline (0 h) were calculated for each time point. The concentration/dose (C0/D) ratio was used as an indicator of TAC metabolism rate.
Results: During a median follow-up of 54 months, 29 recipients developed BKV infection. The BKV group had significantly older donors and showed a significantly larger decrease in TAC concentration at 12 h compared to the non-BKV group (-1.5 vs. 0 ng/mL, P = 0.008). There was no significant difference in pre-transplant C0/D ratios between the two groups. A decrease of ≥ 1.5 ng/mL at 12 h was identified as a significant risk factor for BKV infection (hazard ratio: 2.44, 95% confidence interval: 1.11-5.32, P = 0.026) in a propensity score-based inverse probability of treatment weighting multivariate Cox proportional hazards analysis.
Conclusion: Pre-transplant TAC blood concentration fluctuations, particularly a large decrease at 12 h from baseline, may be associated with increased BKV infection risk.
期刊介绍：
Clinical and Experimental Nephrology is a peer-reviewed monthly journal, officially published by the Japanese Society of Nephrology (JSN) to provide an international forum for the discussion of research and issues relating to the study of nephrology. Out of respect for the founders of the JSN, the title of this journal uses the term “nephrology,” a word created and brought into use with the establishment of the JSN (Japanese Journal of Nephrology, Vol. 2, No. 1, 1960). The journal publishes articles on all aspects of nephrology, including basic, experimental, and clinical research, so as to share the latest research findings and ideas not only with members of the JSN, but with all researchers who wish to contribute to a better understanding of recent advances in nephrology. The journal is unique in that it introduces to an international readership original reports from Japan and also the clinical standards discussed and agreed by JSN.
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