Rycen Jack, Jefferis Julia, Mudge David
Department of Kidney and Transplant Services, Princess Alexandra Hospital, Brisbane, Australia.
Faculty of Medicine, The University of Queensland, Brisbane, Australia.
J Med Case Rep. 2024 Dec 20;18(1):629. doi: 10.1186/s13256-024-04990-6.
Kidney transplant recipients with severe acute respiratory syndrome-coronavirus-2 infection have an increased risk of severe disease and mortality. Nirmaltrevir/ritonavir (Paxlovid) is an effective oral disease-modifying therapy that has been shown to reduce risk of progression to severe disease in high-risk, nonhospitalized adults. However, owing to the potential for serious drug-drug interactions owing to ritonavir-induced inhibition of the CYP3A enzyme, this drug is not suitable option for transplant recipients with mild-moderate severe acute respiratory syndrome-coronavirus-2 infection.
A 57-year-old Caucasian man presented to the emergency department with 48 hours of nausea, vomiting, headaches, and lethargy. At 5 days earlier, he was diagnosed with a mild severe acute respiratory syndrome-coronavirus-2 infection by his general practitioner, who commenced treatment with Paxlovid at 300 mg/100 mg twice daily. Past medical history included kidney transplantation in 2018 for end-stage kidney secondary to hypertensive nephrosclerosis, managed with prednisone, tacrolimus, and mycophenolate. Vaccination status was up-to-date and prophylactic tixagevimab/cilgavimab (Evusheld) had been given > 6 months prior owing to lack of seroconversion. Examination showed a blood pressure of 176/94 mmHg and normal respiratory parameters. Investigations demonstrated a serum creatinine of 213 µmol/L (baseline 130 µmol/L) and tacrolimus trough level of 118 µg/L (baseline 6.9-8.7 µg/L). Treatment included intravenous rehydration, Evusheld and tacrolimus were withheld for 7 days, with recommencement guided by regular therapeutic drug monitoring.
This acute kidney injury was attributed to tacrolimus toxicity resulting from a drug-drug interaction with Paxlovid. While transplant recipients have an increased risk of severe disease, current Australian guidelines recommend against Paxlovid use in adults taking medications that are heavily dependent on CYP3A4 for clearance, including calcineurin and mammalian target of rapamycin inhibitors.
感染严重急性呼吸综合征冠状病毒2的肾移植受者发生重症疾病和死亡的风险增加。奈玛特韦/利托那韦（帕罗韦德）是一种有效的口服病情改善疗法，已被证明可降低高危、非住院成人进展为重症疾病的风险。然而，由于利托那韦诱导的细胞色素P450 3A酶抑制作用可能导致严重的药物相互作用，该药物不适用于轻度至中度感染严重急性呼吸综合征冠状病毒2的移植受者。
一名57岁的白人男性因恶心、呕吐、头痛和嗜睡48小时就诊于急诊科。5天前，他被全科医生诊断为轻度感染严重急性呼吸综合征冠状病毒2，开始接受帕罗韦德治疗，剂量为300毫克/100毫克，每日两次。既往病史包括2018年因高血压性肾硬化继发终末期肾病接受肾移植，使用泼尼松、他克莫司和霉酚酸酯治疗。疫苗接种情况最新，因血清转化未成功，在6个月前已给予预防性替沙格韦单抗/西加韦单抗（恩适得）。检查显示血压为176/94毫米汞柱，呼吸参数正常。检查发现血清肌酐为213微摩尔/升（基线为130微摩尔/升），他克莫司谷浓度为118微克/升（基线为6.9 - 8.7微克/升）。治疗包括静脉补液，停用恩适得和他克莫司7天，并根据定期治疗药物监测结果重新开始用药。
此次急性肾损伤归因于与帕罗韦德的药物相互作用导致的他克莫司毒性。虽然移植受者发生重症疾病的风险增加，但澳大利亚现行指南建议，对于服用严重依赖细胞色素P450 3A4进行清除的药物（包括钙调神经磷酸酶抑制剂和雷帕霉素靶蛋白抑制剂）的成人，不建议使用帕罗韦德。
