Clinical assessment and pathophysiology of Bothrops venom-related acute kidney injury: a scoping review

Abstract Bothrops are one of the most common medically important snakes found in Latin America. Its venom is predominantly hemotoxic and proteolytic, which means that local lesion (edema and redness) and hemorrhagic symptoms are recurrent in envenoming by this snake. Although hemorrhage is usually the major cause of death, snakebite-related acute kidney injury is another potentially fatal clinical complication that may lead to chronic kidney disease. The present review highlights the main studies on Bothrops venom-related acute kidney injury, including observational, cross-sectional, case-control and cohort human studies available up to December 2019. The following descriptors were used according to Medical Subject Headings (MeSH): on Medline/Pubmed and Google Scholar “acute kidney injury” or “kidney disease” and “Bothrops”; on Lilacs and SciELO “kidney disease” or “acute kidney injury” and “Bothrops”. Newcastle-Ottawa quality assessment scale was used to appraise the quality of the cross-sectional and cohort studies included. The selection of more severe patients who looked for health care units and tertiary centers is a risk of bias. Due to the methodological heterogeneity of the studies, a critical analysis of the results was performed based on the hypothesis that the design of the included studies influences the incidence of acute kidney injury. Fifteen human studies (total participants 4624) were included according to stablished criteria. The coagulation abnormalities (hemorrhagic symptoms, abnormal fibrinogen and activated partial thromboplastin time) were associated with acute kidney injury in the most recent studies reported. The findings observed in this review provide up-to-date evidence about the acute kidney injury pathogenesis following Bothrops syndrome. Studies pointed out that coagulation abnormalities comprise the major pathway for acute kidney injury development. This review may improve patient management by primary healthcare providers, allowing earlier diagnosis and treatment of Bothrops venom-related acute kidney injury.

摘要：矛头蝮属（Bothrops）蛇类是拉丁美洲地区最常见的具有医学重要性的蛇类之一。其毒液主要为血液毒性与蛋白水解毒性，因此被该蛇咬伤中毒后，局部损伤（水肿与红斑）及出血症状较为常见。尽管出血通常是致死的主要原因，但蛇伤相关急性肾损伤（acute kidney injury）是另一类潜在致命的临床并发症，可进展为慢性肾脏病。本综述梳理了截至2019年12月已发表的所有矛头蝮毒液相关急性肾损伤的相关研究，涵盖观察性研究、横断面研究、病例对照研究及队列研究等以人为研究对象的研究类型。本研究按照医学主题词表（Medical Subject Headings, MeSH）制定检索策略：在Medline/Pubmed及Google Scholar数据库中，检索式为"急性肾损伤"或"肾脏病" AND "Bothrops"；在Lilacs及SciELO数据库中，检索式为"肾脏病"或"急性肾损伤" AND "Bothrops"。采用纽卡斯尔-渥太华质量评价量表（Newcastle-Ottawa Quality Assessment Scale）对纳入的横断面研究及队列研究进行质量评估。仅纳入前往医疗机构及三级医疗中心就诊的重症患者，该纳入方式可能引入偏倚风险。鉴于纳入研究存在方法学异质性，本综述基于"纳入研究的研究设计会影响急性肾损伤的发生率"这一假说，对研究结果进行了批判性分析。按照既定标准，本综述共纳入15项以人为研究对象的研究，总样本量为4624例受试者。在已发表的最新研究中，凝血功能异常（包括出血症状、纤维蛋白原异常及活化部分凝血活酶时间（activated partial thromboplastin time））与急性肾损伤存在关联。本综述的研究结果为矛头蝮蛇伤综合征后急性肾损伤的发病机制提供了最新证据。多项研究表明，凝血功能异常是急性肾损伤发生的主要通路。本综述可为基层医疗人员优化患者管理提供参考，有助于更早地诊断和治疗矛头蝮毒液相关急性肾损伤。