Kacew S, Bergeron M G
Department of Pharmacology, Faculty of Health Sciences, University of Ottawa, Ontario, Canada.
Toxicol Lett. 1990 May;51(3):241-59; discussion 237-9. doi: 10.1016/0378-4274(90)90067-v.
Aminoglycoside antibiotics play an integral role in antimicrobial chemotherapy. Unfortunately, these drugs are known to cause nephrotoxicity in man and experimental animals. In fact, the incidence of renal dysfunction during the course of clinical treatment with aminoglycoside antibiotics is approximately 10%. Over the past two decades the elucidation of the pathogenesis of aminoglycoside-induced nephrotoxicity has been the subject of numerous investigations. This review describes the recent theories postulated to play a role in the pathogenesis of antibiotic-induced renal damage. In particular, the importance of amino-glycoside levels in the renal cortex or at the membrane binding site is examined in detail. The relevance of antibiotic tissue levels is reflected in the ability of other drugs to modify nephrotoxicity through an alteration in renal aminoglycoside content. The role of factors including age and diet in drug-induced nephrotoxicity is described. In clinical practice, aminoglycoside antibiotics may often be with other agents. The influence of aminoglycoside interaction with other drugs including vancomycin, cephalosporins and cytotoxic drugs is examined in the light of reports that nephrotoxicity is potentiated in these situations. In addition, this review focuses on the role of infection (pyelonephritis and septicemia) and bacterial endotoxin as pathogenic factors involved in aminoglycoside nephrotoxicity. Both the direct influence of endotoxin and the indirect effects of vasoactive mediators and inflammatory processes will be discussed. A multiplicity of factors is involved in the pathogenesis of aminoglycoside-induced nephrotoxicity and these are further amplified in the presence of infection.
氨基糖苷类抗生素在抗菌化疗中发挥着不可或缺的作用。不幸的是，已知这些药物会在人和实验动物中引起肾毒性。事实上，在使用氨基糖苷类抗生素进行临床治疗的过程中，肾功能障碍的发生率约为10%。在过去的二十年里，氨基糖苷类诱导的肾毒性发病机制的阐明一直是众多研究的主题。这篇综述描述了最近提出的在抗生素诱导的肾损伤发病机制中起作用的理论。特别是，详细研究了肾皮质或膜结合位点处氨基糖苷水平的重要性。抗生素组织水平的相关性体现在其他药物通过改变肾脏氨基糖苷含量来改变肾毒性的能力上。描述了包括年龄和饮食等因素在药物诱导的肾毒性中的作用。在临床实践中，氨基糖苷类抗生素经常可能与其他药物联合使用。鉴于有报道称在这些情况下肾毒性会增强，研究了氨基糖苷与其他药物（包括万古霉素、头孢菌素和细胞毒性药物）相互作用的影响。此外，这篇综述重点关注感染（肾盂肾炎和败血症）和细菌内毒素作为参与氨基糖苷肾毒性的致病因素的作用。将讨论内毒素的直接影响以及血管活性介质和炎症过程的间接影响。氨基糖苷类诱导的肾毒性发病机制涉及多种因素，并且在存在感染的情况下这些因素会进一步加剧。
