Guideline for clinical diagnosis and treatment of tuberculosis in kidney transplant recipients in China (2023 edition)
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摘要: 本指南旨在为肾移植受者结核病的临床管理提供全面而实用的指导。首先，概述了肾移植受者结核病的特殊性，强调了其高发生率及临床表现的多样性。为了更好地理解患者的病情，建议在移植前进行结核病相关的评估，并注意移植术后对结核病的监测。在诊断方面，详细介绍了目前常用的结核病诊断方法，并提供了在肾移植受者中的适用性评估。在确诊后，讨论了在免疫抑制药应用的背景下，如何平衡结核病治疗和排斥反应的策略，并关注了潜在的药物相互作用。预防方面，强调了在肾移植前对结核病的筛查。本指南旨在提高医务人员对肾移植受者结核病管理的认知，促进更有效的临床实践，提高受者的生活质量。Abstract: This guideline aims to provide comprehensive and practical guidance for clinical management of tuberculosis in kidney transplant recipients. First, it summarizes the particularity of tuberculosis in kidney transplant recipients, and highlights the high incidence and diverse clinical manifestations. To better understand the patients' conditions, relevant assessment of tuberculosis is recommended before kidney transplantation. Extensive attention should be paid to the monitoring of tuberculosis after kidney transplantation. Regarding the diagnosis, the guideline explicitly introduces common diagnostic approaches for tuberculosis, and evaluates the applicability in kidney transplant recipients. After the diagnosis is confirmed, it discusses how to balance the treatment and rejection of tuberculosis under the background of immunosuppressants, and focuses upon the potential drug interaction. In terms of prevention, it emphasizes the screening of tuberculosis prior to kidney transplantation. This guideline is designed to deepen the understanding of medical staff for tuberculosis management in kidney transplant recipients, promote more effective clinical practice and improve the quality of life of the recipients.
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表 1 证据质量与推荐强度分级
Table 1. Level of evidence and recommended grades
推荐强度 证据级别 治疗或危害 A 1a RCT的系统评价 1b 结果可信区间小的RCT 1c 显示“全或无效应”的任何证据 B 2a 队列研究的系统评价 2b 单个的队列研究（包括低质量的RCT，如失访率>20%者） 2c 基于患者结局的研究 3a 病例对照研究的系统评价 3b 单个病例对照研究 C 4 病例系列报告、低质量队列研究和低质量病例对照研究 D 5 专家意见（即无临床研究支持的仅依据基础研究或临床经验的推测） 
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表 2 推荐意见汇总
Table 2. Summary of recommended opinions
序号 推荐意见 推荐强度 证据级别 1 肾移植受者结核病临床症状多不典型，不同部位的结核病临床表现存在较多差异。发热是多数肾移植术后结核病患者（尤其是肺结核患者）的共同临床表现，常为首发症状，但不具有特异性。对于病原体不明确但仍持续发热的患者，需排除结核病的可能 C 4 2 痰液、支气管冲洗液或支气管肺泡灌洗液、经支气管肺活组织检查、尿液、肺结核和肺外结核病变处行组织活组织检查标本等发现结核分枝杆菌是诊断肾移植术后结核病的金标准，标本应送抗酸杆菌涂片、分枝杆菌分离培养、进一步菌种鉴定和药敏试验以及组织病理检测，但阳性率和培养分离率相对较低，且受标本质量的影响 A 1a 3 Xpert结核分枝杆菌/利福平耐药检测（一种基于Xpert技术的分子诊断试剂盒，可以同时快速检测结核分枝杆菌及是否对利福平耐药）可以在几个小时内提供检测结果，迅速指导诊断和治疗决策，试验灵敏度较高，可用于结核病初筛 D 5 4 Xpert和二代测序技术对结核病均有诊断价值，Xpert联合二代测序、二代测序诊断结核病的灵敏度均高于Xpert检测，特异度相差不大 C 4 5 结核菌素皮肤试验（目前常用的是结核菌素纯蛋白衍生物试验）、γ-干扰素释放试验可用于辅助诊断结核病，两者联合检测阳性率高 B 2a 6 结核菌素皮肤试验可应用于移植前后各个阶段，48~72 h硬结直径>5 mm考虑阳性结果 A 1a 7 影像学检查是肾移植术后结核病的重要诊断手段，特别是肺结核的诊断 B 2c 8 与非移植结核病患者相比，移植受者肺外结核较多见，各器官结核影像学表现与非移植患者类似，缺乏特异性表现，需针对具体临床病例进行综合分析 D 5 9 典型结核组织病理学诊断联合结核病原学依据是结核病诊断的重要标准 D 5 10 所有等待移植的受者及供者均应详细询问卡介苗接种史、结核相关病史、结核病患者接触史及结核菌素皮肤试验和γ-干扰素释放试验筛查史；在移植术前常规对受者行胸部影像学、结核菌素皮肤试验及γ-干扰素释放试验筛查 B 2a 11 活动性结核病是器官捐献和移植的禁忌证 B 2a 12 对潜伏结核感染的活体供者、受者及等待者进行预防性抗结核治疗前，均应仔细评估，以排除活动性结核病 D 5 13 存在潜伏结核感染的活体供者、受者和等待者的预防性治疗方案建议与普通人群基本相同 D 5 14 预防性抗结核治疗尽量在移植前完成，若不能在移植前完成，移植术后应尽快重启；中断治疗后，需对患者病情进行密切监测，并重新评估以判断是否已转变为活动性结核病，并确定是否需要调整或延长抗结核药物治疗的时间 D 5 15 等待移植的患者有肺结核病史并接受过联合、适量、规律及全程治疗，痊愈后可以行移植 D 5 16 建议对肾移植受者肺结核治疗使用与普通人群相同的抗结核药物治疗方案 D 5 初治敏感肺结核患者推荐2HRZE/4HR的标准治疗方案：即4联强化用药（异烟肼、利福平、吡嗪酰胺和乙胺丁醇）2个月，然后持续用药（异烟肼和利福平）4个月 A 1b 17 肺外结核治疗疗程推荐至少12个月；中枢神经系统结核治疗疗程推荐不少于12个月；治疗周期的长短取决于对抗结核治疗的反应性和维持治疗阶段中的用药方案 D 5 18 利福霉素类抗结核药物与免疫抑制药之间的代谢干扰明显增加肾移植术后结核病患者抗结核治疗的复杂性，并明显增加了抗结核药物自身不良反应的发生率 C 4 19 对于接受利福平治疗的受者，推荐及时监测钙调磷酸酶抑制剂和哺乳动物雷帕霉素靶蛋白抑制剂类药物的血药浓度，并增加血药浓度的监测频率，依据血药浓度监测结果及时调整免疫抑制药的剂量 C 4 20 对于接受利福平治疗的受者，推荐应用提高免疫抑制药血药浓度的药物如中药制剂五味子提取物五酯滴丸、五酯胶囊和五酯片，避免因免疫抑制药血药浓度过低导致移植肾排斥反应的发生 B 2b 21 可考虑使用利福布汀代替利福平，以减少利福平与钙调磷酸酶抑制剂和哺乳动物雷帕霉素靶蛋白抑制剂类药物的相互作用 C 4
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表 3 部分抗结核药物对免疫抑制药的影响
Table 3. Effect of some antituberculosis drugs on immunosuppressive agents
免疫抑制药 异烟肼 利福平或利福喷丁 利福布汀 吡嗪
酰胺乙胺
丁醇链霉素 莫西沙星或左氧氟沙星 糖皮质激素 提高糖皮质激素水平，增加其不良反应（肝代谢抑制） 降低糖皮质激素水平及效果（肝代谢诱导） 影响较小（肝代谢诱导较弱） 无影响 无影响 无影响 增加肌腱相关的不良反应 环孢素 无影响 降低环孢素血药浓度及疗效（肝代谢诱导） 影响较小（肝代谢诱导较弱） 无影响 无影响 增加肾毒性的风险（增加毒性） 增加环孢素血药浓度（仅左氧氟沙星） 他克莫司 无影响 降低他克莫司血药浓度及疗效（肝代谢诱导） 影响较小（肝代谢诱导较弱） 无影响 无影响 增加肾毒性的风险（增加毒性） 无影响 西罗莫司 无影响 降低西罗莫司血药浓度及疗效（肝代谢诱导） 影响较小（肝代谢诱导较弱） 无影响 无影响 无影响 无影响 吗替麦考酚酯 无影响 使用替代或监测吗替麦考酚酯水平，与之联合使用可降低吗替麦考酚酯血药浓度及疗效（肠肝循环障碍） 降低吗替麦考酚酯的血药浓度 无影响 无影响 无影响 降低吗替麦考酚酯的血药浓度
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