Nakagawa Shunsaku, Ikuta Keiko, Masuda Takashi, Terada Tomohiro
Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, 54 Shogoin-Kawahara-Cho, Sakyo-Ku, Kyoto, 606-8507, Japan.
Int J Clin Oncol. 2025 Jul 17. doi: 10.1007/s10147-025-02832-z.
Renal dysfunction is common in patients with cancer and affects their pharmacokinetics, thereby altering treatment efficacy and safety. This review outlines the principles of dose adjustment based on renal function and highlights specific issues in patients undergoing dialysis or with proteinuria. In patients undergoing dialysis, dose adjustment can be rational if drug properties such as molecular weight and protein binding are considered. Metabolites of some drugs, such as fluorouracil (5-FU), may accumulate in patients with impaired renal function, thereby increasing the risk of toxicity. For oxaliplatin, increased platinum exposure in patients undergoing dialysis does not necessarily increase toxicity, possibly because reactive platinum species are eliminated independent of renal function. Proteinuria can lead to reduced drug exposure to monoclonal antibodies owing to abnormal urinary excretion. The early detection and management of drug-induced kidney injuries are essential. These strategies include identifying risk factors, adjusting doses, and implementing monitoring systems. Protocol-based approaches, such as pharmacist-led monitoring, can improve cancer pharmacotherapy. Automated systems and AI-based models have also been explored for risk prediction. Future studies should focus on deepening our understanding of pharmacokinetics in patients with advanced chronic kidney disease (CKD) or those on dialysis. Multidisciplinary collaboration in onco-nephrology is important to improve cancer care in this growing population.
肾功能不全在癌症患者中很常见,会影响其药代动力学,从而改变治疗效果和安全性。本综述概述了基于肾功能进行剂量调整的原则,并强调了透析患者或蛋白尿患者的具体问题。对于透析患者,如果考虑分子量和蛋白结合等药物特性,剂量调整可能是合理的。一些药物的代谢产物,如氟尿嘧啶(5-FU),可能在肾功能受损的患者中蓄积,从而增加毒性风险。对于奥沙利铂,透析患者铂暴露增加不一定会增加毒性,可能是因为活性铂物种的消除与肾功能无关。蛋白尿可导致单克隆抗体的药物暴露减少,原因是尿液排泄异常。药物性肾损伤的早期检测和管理至关重要。这些策略包括识别风险因素、调整剂量和实施监测系统。基于方案的方法,如药剂师主导的监测,可以改善癌症药物治疗。自动系统和基于人工智能的模型也已用于风险预测。未来的研究应侧重于加深我们对晚期慢性肾脏病(CKD)患者或透析患者药代动力学的理解。肿瘤肾脏病学的多学科合作对于改善这一不断增长人群的癌症护理至关重要。