Interdisciplinary Toxicology Program.
Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia 30602.
Toxicol Sci. 2018 Aug 1;164(2):379-390. doi: 10.1093/toxsci/kfy159.
The kidney consists of numerous cell types organized into the nephron, which is the basic functional unit of the kidney. Any stimuli that induce loss of these cells can induce kidney damage and renal failure. The cause of renal failure can be intrinsic or extrinsic. Extrinsic causes include cardiovascular disease, obesity, diabetes, sepsis, and lung and liver failure. Intrinsic causes include glomerular nephritis, polycystic kidney disease, renal fibrosis, tubular cell death, and stones. The kidney plays a prominent role in mediating the toxicity of numerous drugs, environmental pollutants and natural substances. Drugs known to be nephrotoxic include several cancer therapeutics, drugs of abuse, antibiotics, and radiocontrast agents. Environmental pollutants known to target the kidney include cadmium, mercury, arsenic, lead, trichloroethylene, bromate, brominated-flame retardants, diglycolic acid, and ethylene glycol. Natural nephrotoxicants include aristolochic acids and mycotoxins such as ochratoxin, fumonisin B1, and citrinin. There are several common characteristics between mechanisms of renal failure induced by nephrotoxicants and extrinsic causes. This common ground exists primarily due to similarities in the molecular mechanisms mediating renal cell death. This review summarizes the current state of the field of nephrotoxicity. It emphasizes integrating our understanding of nephrotoxicity with pathological-induced renal failure. Such approaches are needed to address major questions in the field, which include the diagnosis, prognosis and treatment of both acute and chronic renal failure, and the progression of acute kidney injury to chronic kidney disease.
肾脏由众多细胞类型组成，这些细胞类型组织成肾单位，这是肾脏的基本功能单位。任何导致这些细胞丢失的刺激都可能导致肾脏损伤和肾衰竭。肾衰竭的原因可以是内在的或外在的。外在原因包括心血管疾病、肥胖、糖尿病、败血症以及肺和肝功能衰竭。内在原因包括肾小球肾炎、多囊肾病、肾纤维化、肾小管细胞死亡和结石。肾脏在介导许多药物、环境污染物和天然物质的毒性方面起着重要作用。已知具有肾毒性的药物包括几种癌症治疗药物、滥用药物、抗生素和造影剂。已知靶向肾脏的环境污染物包括镉、汞、砷、铅、三氯乙烯、溴酸盐、溴化阻燃剂、二甘醇和乙二醇。天然肾毒物包括马兜铃酸和霉菌毒素，如黄曲霉毒素、伏马菌素 B1 和桔霉素。肾毒物和外在原因引起的肾衰竭机制之间有几个共同特征。这种共同点主要是由于介导肾细胞死亡的分子机制相似所致。这篇综述总结了肾毒性领域的现状。它强调了将我们对肾毒性的理解与病理性肾衰竭结合起来。这些方法是解决该领域的主要问题所必需的，这些问题包括急性和慢性肾衰竭的诊断、预后和治疗，以及急性肾损伤向慢性肾脏病的进展。
