Latcha Sheron, Jaimes Edgar A, Patil Sujata, Glezerman Ilya G, Mehta Swati, Flombaum Carlos D
Department of Medicine, Renal Service and.
Renal Division, Weill-Cornell Medical College, New York, New York.
Clin J Am Soc Nephrol. 2016 Jul 7;11(7):1173-1179. doi: 10.2215/CJN.08070715. Epub 2016 Apr 12.
Nephrotoxicity remains the dose-limiting side effect of cisplatin, an effective chemotherapeutic agent with applications across diverse tumor types. This study presents data on renal outcomes across multiple tumor types in 821 adults. We report on incidence of AKI, initial and long-term changes in eGFR after cisplatin, and relationships between cumulative dose, initial eGFR, age, sex, and long-term renal function.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was a retrospective study of adult patients treated with cisplatin from January 1, 2000 to September 21, 2011 who had survived ≥5 years after initial dose. The Modification of Diet in Renal Disease equation was used to calculate eGFR. AKI was defined as an increase from the baseline creatinine of >25% within 30 days after the first cycle of cisplatin. Chi-squared tests were done to evaluate the relationships between categorical or ordinal variables; ANOVAs or t tests were used to evaluate continuous or categorical variables. Changes in eGFR over time were evaluated in a growth curve model.
Mean follow-up was 6 years (25th and 75th percentiles, 4 and 9 years). AKI occurred in 31.5% of patients, with a median initial decline in eGFR of 10 ml/min per 1.73 m(2) (25th and 75th percentiles, -41.5 and -23.3 ml/min per 1.73 m(2)). At any time point after the first cycle of cisplatin, <3% of patients progressed to eGFR<29 ml/min per 1.73 m(2), and none were known to be on dialysis. Age was associated with a higher risk for AKI after cisplatin. Compared with age <25 years old, the odds ratios for AKI versus no AKI are 1.22 for >26-44 years old (95% confidence interval [95% CI], 0.60 to 2.4), 1.54 for >45-65 years old (95% CI, 0.78 to 3), and 2.96 for >66 years old (95% CI, 1.4 to 6.1). The lowest dose categories of cisplatin (≤100 and 101-250 mg/m(2)) are associated with increases in eGFR (P=0.06 and P=0.02, respectively) compared with the highest dose category (>701 mg/m(2)).
This is the largest study of adult patients with cancer who received cisplatin for treatment across multiple tumor types. Most patients experience small but permanent declines in eGFR, but none progressed to ESRD requiring hemodialysis.
肾毒性仍然是顺铂的剂量限制性副作用，顺铂是一种有效的化疗药物，应用于多种肿瘤类型。本研究展示了821名成年人中多种肿瘤类型的肾脏结局数据。我们报告急性肾损伤（AKI）的发生率、顺铂治疗后估算肾小球滤过率（eGFR）的初始和长期变化，以及累积剂量、初始eGFR、年龄、性别与长期肾功能之间的关系。
设计、设置、参与者与测量：这是一项对2000年1月1日至2011年9月21日接受顺铂治疗且初始剂量后存活≥5年的成年患者的回顾性研究。采用肾脏病饮食改良公式计算eGFR。AKI定义为顺铂首个疗程后30天内肌酐较基线升高>25%。采用卡方检验评估分类或有序变量之间的关系；采用方差分析或t检验评估连续或分类变量。在生长曲线模型中评估eGFR随时间的变化。
平均随访6年（第25和第75百分位数分别为4年和9年）。31.5%的患者发生AKI，eGFR初始下降中位数为每1.73 m² 10 ml/min（第25和第75百分位数分别为每1.73 m² -41.5和-23.3 ml/min）。在顺铂首个疗程后的任何时间点，<3%的患者进展至eGFR<每1.73 m² 29 ml/min，且无人进行透析。年龄与顺铂治疗后发生AKI的较高风险相关。与年龄<25岁相比，26 - 44岁AKI与无AKI的比值比为1.22（95%置信区间[95% CI]，0.60至2.4），45 - 65岁为1.54（95% CI，0.78至3），>66岁为2.96（95% CI，1.4至6.1）。与最高剂量类别（>701 mg/m²）相比，顺铂最低剂量类别（≤100和101 - 250 mg/m²）与eGFR升高相关（分别为P = 0.06和P = 0.02）。
这是对接受顺铂治疗的多种肿瘤类型成年癌症患者进行的最大规模研究。大多数患者的eGFR出现小幅度但永久性的下降，但无人进展至需要血液透析的终末期肾病（ESRD）。
