Renal Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
Weill Cornell Medical College, New York, New York.
Kidney360. 2024 Aug 1;5(8):1094-1100. doi: 10.34067/KID.0000000000000464. Epub 2024 May 30.
Serotonin receptor antagonists reduce the incidence of AKI in patients receiving cisplatin as chemotherapy. New-generation serotonin receptors do not offer any additional advantage in terms of protection from cisplatin induced AKI.
Cisplatin is an effective first-line therapy for a variety of cancers. Cisplatin is highly emetogenic and resulting volume depletion can contribute to AKI. Antiemetic drugs, such as 5-hydroxytryptamine type 3 receptor antagonists (5-HTRAs), are commonly prescribed to prevent this complication. Preclinical studies suggest first-generation 5-HTRAs may alter the renal clearance and increase cisplatin toxicity. This retrospective study evaluated whether different 5-HTRAs modify the risk of AKI in patients receiving cisplatin.
Patients with cancer who received cisplatin between January 1, 2010, and December 31, 2016, were included. Patients older than 18 years with available data for baseline and post-treatment serum creatinine, cisplatin cumulative dose, and administration of 5-HTRAs, including first-generation (ondansetron, granisetron, and ramosetron) and second-generation (palonosetron), were analyzed. AKI was defined as 1.5× increase in serum creatinine. Fisher exact and Wilcoxon rank-sum tests were used to assess univariable associations between baseline covariates and AKI and logistic regression for multivariable associations with AKI.
Of 8703 patients identified with cisplatin exposure, 6889 were included. A total of 3881 patients (56.3%) received at least one 5-HTRA, including palonosetron (3750, 54.4%), ondansetron (1399, 20.3%), and granisetron (11, 0.2%). AKI developed in 1666 patients (24.2%) after cisplatin therapy. Patients who received any 5-HTRAs were less likely to experience AKI as compared with patients who did not (22.6% versus 26.2%, = 0.001). Older age, male sex, African ethnicity, and cumulative cisplatin dose were univariably associated with higher risk of AKI ( < 0.001). After adjusting for these variables, use of any of these antiemetic drugs was protective for AKI (odds ratio, 0.84; 95% confidence interval, 0.75 to 0.94; = 0.003) with no difference detected between type of 5-HTRA.
Nephrotoxicity continues to be a concern after cisplatin therapy. Given its emetogenic nature, use of antiemetic drugs, such as 5-HTRAs, can lessen emesis and lower risk of kidney injury. This retrospective analysis supports use of any 5-HTRAs to lower risk of AKI.
5-羟色胺受体拮抗剂可降低顺铂化疗患者急性肾损伤的发生率。新一代 5-羟色胺受体在预防顺铂引起的急性肾损伤方面没有任何额外的优势。
顺铂是多种癌症的有效一线治疗药物。顺铂具有高度致吐性，由此导致的血容量减少可能导致急性肾损伤。止吐药，如 5-羟色胺 3 型受体拮抗剂（5-HTRAs），通常被用于预防这种并发症。临床前研究表明，第一代 5-HTRAs 可能会改变肾脏清除率并增加顺铂的毒性。本回顾性研究评估了不同 5-HTRAs 是否会改变接受顺铂治疗的患者发生急性肾损伤的风险。
纳入 2010 年 1 月 1 日至 2016 年 12 月 31 日期间接受顺铂治疗的癌症患者。纳入年龄大于 18 岁、基线和治疗后血清肌酐、顺铂累积剂量以及 5-HTRAs（包括第一代[昂丹司琼、格拉司琼和雷莫司琼]和第二代[帕洛诺司琼]）使用数据均可用的患者。急性肾损伤定义为血清肌酐升高 1.5 倍。使用 Fisher 确切检验和 Wilcoxon 秩和检验评估基线协变量与急性肾损伤之间的单变量相关性，并使用 logistic 回归进行多变量相关性分析。
在确定的 8703 例接受顺铂暴露的患者中，有 6889 例被纳入研究。共有 3881 例（56.3%）患者接受了至少一种 5-HTRA，包括帕洛诺司琼（3750 例，54.4%）、昂丹司琼（1399 例，20.3%）和格拉司琼（11 例，0.2%）。在接受顺铂治疗后，有 1666 例（24.2%）患者发生急性肾损伤。与未使用 5-HTRAs 的患者相比，使用任何一种 5-HTRAs 的患者发生急性肾损伤的可能性较低（22.6%与 26.2%， < 0.001）。年龄较大、男性、非洲裔和累积顺铂剂量是与急性肾损伤风险增加相关的单变量因素（ < 0.001）。在校正这些变量后，使用这些止吐药物中的任何一种药物都可以预防急性肾损伤（比值比，0.84；95%置信区间，0.75 至 0.94； < 0.001），并且在使用不同类型 5-HTRA 时没有差异。
顺铂治疗后肾毒性仍然是一个令人关注的问题。鉴于其致吐作用，使用止吐药，如 5-HTRAs，可以减少呕吐并降低肾脏损伤的风险。本回顾性分析支持使用任何 5-HTRAs 来降低急性肾损伤的风险。
