顺铂治疗期间儿童急性肾损伤及其与顺铂治疗后2至6个月肾脏结局的关联：一项多中心前瞻性观察研究。
Acute kidney injury during cisplatin therapy and associations with kidney outcomes 2 to 6 months post-cisplatin in children: a multi-centre, prospective observational study.
作者信息
McMahon Kelly R, Lebel Asaf, Rassekh Shahrad Rod, Schultz Kirk R, Blydt-Hansen Tom D, Cuvelier Geoffrey D E, Mammen Cherry, Pinsk Maury, Carleton Bruce C, Tsuyuki Ross T, Ross Colin J D, Huynh Louis, Yordanova Mariya, Crépeau-Hubert Frédérik, Wang Stella, Palijan Ana, Lee Jasmine, Boyko Debbie, Zappitelli Michael
机构信息
Department of Pediatrics, Division of Nephrology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
Faculty of Medicine, Division of Experimental Medicine, McGill University, Montreal, QC, Canada.
出版信息
Pediatr Nephrol. 2023 May;38(5):1667-1685. doi: 10.1007/s00467-022-05745-5. Epub 2022 Oct 19.
BACKGROUND
Few studies describe acute kidney injury (AKI) burden during paediatric cisplatin therapy and post-cisplatin kidney outcomes. We determined risk factors for and rate of (1) AKI during cisplatin therapy, (2) chronic kidney disease (CKD) and hypertension 2-6 months post-cisplatin, and (3) whether AKI is associated with 2-6-month outcomes.
METHODS
This prospective cohort study enrolled children (aged < 18 years at cancer diagnosis) treated with cisplatin from twelve Canadian hospitals. AKI during cisplatin therapy (primary exposure) was defined based on Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (≥ stage one). Severe electrolyte abnormalities (secondary exposure) included ≥ grade three hypophosphatemia, hypokalemia, or hypomagnesemia (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0). CKD was albuminuria or decreased kidney function for age (KDIGO guidelines). Hypertension was defined based on the 2017 American Academy of Pediatrics guidelines.
RESULTS
Of 159 children (median [interquartile range [IQR]] age: 6 [2-12] years), 73/159 (46%) participants developed AKI and 55/159 (35%) experienced severe electrolyte abnormalities during cisplatin therapy. At median [IQR] 90 [76-110] days post-cisplatin, 53/119 (45%) had CKD and 18/128 (14%) developed hypertension. In multivariable analyses, AKI was not associated with 2-6-month CKD or hypertension. Severe electrolyte abnormalities during cisplatin were associated with having 2-6-month CKD or hypertension (adjusted odds ratio (AdjOR) [95% CI]: 2.65 [1.04-6.74]). Having both AKI and severe electrolyte abnormalities was associated with 2-6-month hypertension (AdjOR [95% CI]: 3.64 [1.05-12.62]).
CONCLUSIONS
Severe electrolyte abnormalities were associated with kidney outcomes. Cisplatin dose optimization to reduce toxicity and clear post-cisplatin kidney follow-up guidelines are needed. A higher resolution version of the Graphical abstract is available as Supplementary information.
背景
很少有研究描述儿童顺铂治疗期间急性肾损伤（AKI）的负担和顺铂治疗后肾脏的转归情况。我们确定了以下方面的危险因素及发生率：（1）顺铂治疗期间的AKI；（2）顺铂治疗后2至6个月的慢性肾脏病（CKD）和高血压；（3）AKI是否与2至6个月的转归相关。
方法
这项前瞻性队列研究纳入了来自加拿大12家医院接受顺铂治疗的儿童（癌症诊断时年龄＜18岁）。顺铂治疗期间的AKI（主要暴露因素）根据肾脏病改善全球预后（KDIGO）血清肌酐标准（≥1期）定义。严重电解质异常（次要暴露因素）包括≥3级低磷血症、低钾血症或低镁血症（美国国立癌症研究所不良事件通用术语标准第4.0版）。CKD根据年龄的蛋白尿或肾功能下降情况（KDIGO指南）定义。高血压根据2017年美国儿科学会指南定义。
结果
159名儿童（中位年龄[四分位间距[IQR]]：6[2 - 12]岁）中，73/159（46%）的参与者在顺铂治疗期间发生了AKI，55/159（35%）出现了严重电解质异常。在顺铂治疗后中位[IQR]90[76 - 110]天，53/119（45%）患有CKD，18/128（14%）发生了高血压。在多变量分析中，AKI与2至6个月时的CKD或高血压无关。顺铂治疗期间的严重电解质异常与2至6个月时的CKD或高血压相关（校正比值比（AdjOR）[95%置信区间]：2.65[1.04 - 6.74]）。同时发生AKI和严重电解质异常与2至6个月时的高血压相关（AdjOR[95%置信区间]：3.64[1.05 - 12.62]）。
结论
严重电解质异常与肾脏转归相关。需要优化顺铂剂量以降低毒性，并明确顺铂治疗后肾脏的随访指南。更高分辨率的图形摘要可作为补充信息获取。
Zotero 插件