Yao Xin, Panichpisal Kessarin, Kurtzman Neil, Nugent Kenneth
Department of Internal Medicine, Texas Tech University Health Science Center, Lubbock, Texas 79430, USA.
Am J Med Sci. 2007 Aug;334(2):115-24. doi: 10.1097/MAJ.0b013e31812dfe1e.
Cisplatin is a major antineoplastic drug for the treatment of solid tumors, but it has dose-dependent renal toxicity.
We reviewed clinical and experimental literature on cisplatin nephrotoxicity to identify new information on the mechanism of injury and potential approaches to prevention and/or treatment.
Unbound cisplatin is freely filtered at the glomerulus and taken up into renal tubular cells mainly by a transport-mediated process. The drug is at least partially metabolized into toxic species. Cisplatin has multiple intracellular effects, including regulating genes, causing direct cytotoxicity with reactive oxygen species, activating mitogen-activated protein kinases, inducing apoptosis, and stimulating inflammation and fibrogenesis. These events cause tubular damage and tubular dysfunction with sodium, potassium, and magnesium wasting. Most patients have a reversible decrease in glomerular filtration, but some have an irreversible decrease in glomerular filtration. Volume expansion and saline diuresis remain the most effective preventive strategies.
Understanding the mechanisms of injury has led to multiple approaches to prevention. Furthermore, the experimental approaches in these studies with cisplatin are potentially applicable to other drugs causing renal dysfunction.
顺铂是治疗实体瘤的主要抗肿瘤药物，但具有剂量依赖性肾毒性。
我们回顾了关于顺铂肾毒性的临床和实验文献，以确定损伤机制的新信息以及预防和/或治疗的潜在方法。
未结合的顺铂在肾小球自由滤过，主要通过转运介导的过程被肾小管细胞摄取。该药物至少部分代谢为有毒物质。顺铂具有多种细胞内效应，包括调节基因、通过活性氧导致直接细胞毒性、激活丝裂原活化蛋白激酶、诱导凋亡以及刺激炎症和纤维化形成。这些事件导致肾小管损伤和肾小管功能障碍，伴有钠、钾和镁的流失。大多数患者肾小球滤过率有可逆性下降，但有些患者肾小球滤过率有不可逆性下降。容量扩张和盐水利尿仍然是最有效的预防策略。
对损伤机制的理解带来了多种预防方法。此外，这些顺铂研究中的实验方法可能适用于其他导致肾功能障碍的药物。
