Money Mary Elizabeth, Hamroun Aghiles, Shu Yan, Matthews Carolyn, Ahmed Eltayeb Sara, Ciarimboli Giuliano, Metz Christine Noel
Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD, United States.
Department of Medicine, Meritus Medical Center, Hagerstown, MD, United States.
Front Oncol. 2021 Feb 26;11:607574. doi: 10.3389/fonc.2021.607574. eCollection 2021.
After more than four decades of post-approval, cisplatin is still an important treatment for numerous cancers. However, acute kidney injury (AKI), defined as significant impairment of renal filtration as discussed below, is the major limiting side effect of cisplatin, occurring in approximately 30% of patients (25-33% after the first course). Cisplatin also damages the kidneys' ability to reabsorb magnesium in 40-100% of patients, with collateral health risks due to subsequent hypomagnesemia. Multiple methods and drugs have been proposed for preventing cisplatin-induced AKI, including saline infusion with or without mannitol, which has not always prevented AKI and has been found to activate a cellular stress response in renal tubular cells. While numerous reports and trials, as well as the National Comprehensive Cancer Network (NCCN), support premedication with magnesium and hydration, this practice has not been universally accepted. Many clinics administer intravenous magnesium (IV) only after identification of hypomagnesemia post-cisplatin treatment, thus placing patients at risk for AKI and chronic renal loss of magnesium. We present the following case report and additional supporting evidence identifying the immediate effect of IV magnesium prior to intraperitoneal cisplatin for cycle 4 because of documented hypomagnesemia resulting in normalization of oliguria, which had been experienced for the first three cycles. The patient subsequently requested and received IV magnesium before cisplatin for the next two cycles with continuation of normal urinary output. The effect of pretreatment with IV magnesium on urine output following cisplatin has not been previously reported and further supports pre-cisplatin administration. In addition, two recent meta-analyses of clinical trials and pre-clinical research are reviewed that demonstrate effectiveness of magnesium pretreatment to preventing AKI without reducing its chemotherapeutic efficacy. This case report with additional evidence supports the adoption of administration of 1-3 g IV magnesium before cisplatin as best practice to prevent cisplatin induced AKI and hypomagnesemia regardless of patient baseline serum magnesium levels.
在获批上市四十多年后,顺铂仍是众多癌症的重要治疗药物。然而,急性肾损伤(AKI),如下文所述,定义为肾脏滤过功能的显著损害,是顺铂的主要限制性副作用,约30%的患者会出现(首个疗程后发生率为25 - 33%)。顺铂还会损害40 - 100%患者肾脏重吸收镁的能力,随后的低镁血症会带来附带的健康风险。已提出多种预防顺铂诱导的AKI的方法和药物,包括输注生理盐水(加或不加甘露醇),但这并不总能预防AKI,且已发现其会激活肾小管细胞中的细胞应激反应。尽管众多报告、试验以及美国国立综合癌症网络(NCCN)都支持使用镁剂预处理和水化,但这种做法尚未被普遍接受。许多诊所仅在顺铂治疗后发现低镁血症时才给予静脉注射镁剂(IV),从而使患者面临发生AKI和慢性肾脏镁流失的风险。我们呈现以下病例报告及其他支持性证据,该证据表明由于记录到低镁血症导致少尿在第4周期腹腔内注射顺铂前静脉注射镁剂后少尿恢复正常,在前三个周期中患者一直存在少尿情况。该患者随后在接下来的两个周期中在顺铂治疗前要求并接受了静脉注射镁剂,尿量持续正常。此前尚未报道静脉注射镁剂预处理对顺铂治疗后尿量的影响,这进一步支持了顺铂治疗前给药。此外,本文回顾了两项近期的临床试验和临床前研究的荟萃分析,这些分析表明镁剂预处理可有效预防AKI且不降低其化疗疗效。该病例报告及其他证据支持在顺铂治疗前静脉注射1 - 3 g镁剂作为预防顺铂诱导的AKI和低镁血症的最佳做法,无论患者基线血清镁水平如何。