Renal Service, Memorial Sloan Kettering Cancer Center, New York, NY.
Semin Nephrol. 2020 Jan;40(1):49-58. doi: 10.1016/j.semnephrol.2019.12.006.
The incidence of kidney cancer has been increasing steadily and, until recently, there was a substantial lack of effective therapies for a cancer that is now among the 10 most common cancers in men and women. During the past 10 years, novel therapies have been developed including antiangiogenic drugs targeting vascular endothelial growth factor and its receptors, immune checkpoint inhibitors, and mammalian target of rapamycin inhibitors that have resulted in a significant improvement in clinical outcomes in a traditionally difficult-to-treat cancer. These new drugs, however, also have important side effects and toxicities that often have an impact on the treatment of these patients. The use of anti-angiogenic drugs often results in the development of hypertension and, less frequently, varying degrees of proteinuria including nephrotic range proteinuria. A variety of agents are used for the treatment of hypertension and proteinuria including blockers of the renin angiotensin system and calcium channel blockers, but there are no randomized clinical trials comparing different therapeutic agents in these patients. Immune checkpoint inhibitors have become one of the cornerstones of therapy in kidney cancer, but their use is linked to a variety of side effects that affect almost every organ and resemble autoimmune diseases. In the kidney, these drugs can induce acute interstitial nephritis in close to 5% of patients with varying degrees of severity that in some cases require discontinuation of treatment and systemic treatment with corticosteroids. Although mammalian target of rapamycin inhibitors now also are part of the therapeutic armamentarium available for these patients, all clinical trials have been performed in patients with normal renal function and therefore their effects in patients with abnormal renal function are not known.
肾癌的发病率一直在稳步上升，直到最近，对于这种在男性和女性中最常见的癌症之一，仍然缺乏有效的治疗方法。在过去的 10 年中，已经开发出了新型疗法，包括针对血管内皮生长因子及其受体的抗血管生成药物、免疫检查点抑制剂和哺乳动物雷帕霉素靶蛋白抑制剂，这些疗法显著改善了传统上难以治疗的癌症的临床结局。然而，这些新药也有重要的副作用和毒性，经常会影响这些患者的治疗。抗血管生成药物的使用常常导致高血压的发生，并且不太常见的是，蛋白尿的程度不同，包括肾病范围的蛋白尿。有多种药物可用于治疗高血压和蛋白尿，包括肾素-血管紧张素系统阻滞剂和钙通道阻滞剂，但在这些患者中，尚无比较不同治疗药物的随机临床试验。免疫检查点抑制剂已成为肾癌治疗的基石之一，但它们的使用与各种副作用相关，这些副作用几乎影响到每个器官，并类似于自身免疫性疾病。在肾脏中，这些药物可导致近 5%的患者发生不同程度的急性间质性肾炎，在某些情况下需要停止治疗并使用皮质类固醇进行全身治疗。尽管雷帕霉素靶蛋白抑制剂现在也成为这些患者的治疗手段之一，但所有临床试验都是在肾功能正常的患者中进行的，因此，这些药物在肾功能异常的患者中的作用尚不清楚。
