Granata Simona, Carratù Pierluigi, Stallone Giovanni, Zaza Gianluigi
Renal Unit, Department of Medicine, University-Hospital of Verona, Verona, Italy.
Division of Internal Medicine, Clinica Medica "A. Murri", Department of Biomedical Sciences and Human Oncology, "Aldo Moro" University of Bari, Bari, Italy.
Front Pharmacol. 2021 Aug 23;12:710543. doi: 10.3389/fphar.2021.710543. eCollection 2021.
Kidney transplant recipients are at high risk of developing severe COVID-19 due to the coexistence of several transplant-related comorbidities (e.g., cardiovascular disease, diabetes) and chronic immunosuppression. As a consequence, a large part of SARS-CoV-2 infected patients have been managed with a reduction of immunosuppression. The mTOR-I, together with antimetabolites, have been often discontinued in order to minimize the risk of pulmonary toxicity and to antagonize pharmacological interaction with antiviral/anti-inflammatory drugs. However, at our opinion, this therapeutic strategy, although justified in kidney transplant recipients with severe COVID-19, should be carefully evaluated in asymptomatic/paucisymptomatic patients in order to avoid the onset of acute allograft rejections, to potentially exploit the mTOR-I antiviral properties, to reduce proliferation of conventional T lymphocytes (which could mitigate the cytokine storm) and to preserve Treg growth/activity which could reduce the risk of progression to severe disease. In this review, we discuss the current literature regarding the therapeutic potential of mTOR-Is in kidney transplant recipients with COVID-19 with a focus on pulmonary fibrosis.
由于存在多种与移植相关的合并症（如心血管疾病、糖尿病）以及慢性免疫抑制，肾移植受者感染重症 COVID-19 的风险很高。因此，很大一部分感染 SARS-CoV-2 的患者接受了免疫抑制的减量治疗。为了将肺部毒性风险降至最低并对抗与抗病毒/抗炎药物的药理相互作用，mTOR 抑制剂与抗代谢药物常常被停用。然而，我们认为，这种治疗策略虽然在患有重症 COVID-19 的肾移植受者中是合理的，但在无症状/症状轻微的患者中应仔细评估，以避免急性移植肾排斥反应的发生，有可能利用 mTOR 抑制剂的抗病毒特性，减少传统 T 淋巴细胞的增殖（这可能减轻细胞因子风暴），并维持调节性 T 细胞的生长/活性，这可能降低进展为重症疾病的风险。在这篇综述中，我们讨论了当前关于 mTOR 抑制剂在 COVID-19 肾移植受者中的治疗潜力的文献，重点关注肺纤维化。
