Inflammation and kidney involvement in human viral diseases caused by SARS-CoV-2, HIV, HCV and HBV

Abstract Inflammation is closely related to renal diseases. This is particularly true for renal diseases caused by infections as in viral diseases. In this review, we highlight the inflammatory mechanisms that underlie kidney dysfunction in SARS-CoV-2, human immunodeficiency (HIV), hepatitis C (HCV), and hepatitis B (HBV) infections. The pathophysiology of renal involvement in COVID-19 is complex, but kidney damage is frequent, and the prognosis is worse when it happens. Virus-like particles were demonstrated mostly in renal tubular epithelial cells and podocytes, which suggest that SARS-CoV-2 directly affects the kidneys. SARS-CoV-2 uses the angiotensin-converting enzyme 2 receptor, which is found in endothelial cells, to infect the human host cells. Critical patients with SARS-CoV-2-associated acute kidney injury (AKI) show an increase in inflammatory cytokines (IL-1β, IL-8, IFN-γ, TNF-α), known as cytokine storm that favors renal dysfunction by causing intrarenal inflammation, increased vascular permeability, volume depletion, thromboembolic events in microvasculature and persistent local inflammation. Besides AKI, SARS-CoV-2 can also cause glomerular disease, as other viral infections such as in HIV, HBV and HCV. HIV-infected patients present chronic inflammation that can lead to a number of renal diseases. Proinflammatory cytokines and TNF-induced apoptosis are some of the underlying mechanisms that may explain the virus-induced renal diseases that are here reviewed.

摘要 炎症与肾脏疾病密切相关，对于病毒性感染引发的肾脏疾病而言尤为如此。本综述重点阐述了严重急性呼吸综合征冠状病毒2（SARS-CoV-2）、人类免疫缺陷病毒（HIV）、丙型肝炎病毒（HCV）以及乙型肝炎病毒（HBV）感染所导致的肾功能异常的炎症机制。新型冠状病毒肺炎（COVID-19）中肾脏受累的病理生理学机制较为复杂，肾脏损伤十分常见，且一旦发生则预后更差。研究人员多在肾小管上皮细胞（renal tubular epithelial cells）和足细胞（podocytes）中观察到病毒样颗粒，这提示严重急性呼吸综合征冠状病毒2可直接侵袭肾脏。该病毒可通过内皮细胞（endothelial cells）表面表达的血管紧张素转换酶2（ACE2）受体感染人体宿主细胞。合并严重急性呼吸综合征冠状病毒2相关急性肾损伤（AKI）的重症患者体内促炎细胞因子（IL-1β、IL-8、IFN-γ、TNF-α）水平升高，即所谓的细胞因子风暴（cytokine storm），该风暴可通过引发肾内炎症、血管通透性增加、血容量不足、微血管血栓栓塞事件以及持续性局部炎症，进而诱发肾功能异常。除急性肾损伤外，严重急性呼吸综合征冠状病毒2还可引发肾小球疾病（glomerular disease），这与人类免疫缺陷病毒、乙型肝炎病毒以及丙型肝炎病毒等其他病毒感染所致的肾脏病变类似。人类免疫缺陷病毒感染者会出现慢性炎症状态，进而引发多种肾脏疾病。促炎细胞因子以及肿瘤坏死因子（TNF）诱导的细胞凋亡（apoptosis），是本综述所探讨的病毒诱导肾脏疾病的部分潜在发病机制。