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基于静脉注射顺铂后发生严重急性肾损伤的预测,建立并外部验证一种简单风险评分的推导:队列研究。

Derivation and external validation of a simple risk score for predicting severe acute kidney injury after intravenous cisplatin: cohort study.

机构信息

Division of Renal Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA

Adult Survivorship Program, Dana-Farber Cancer Institute, Boston, MA, USA.

出版信息

BMJ. 2024 Mar 27;384:e077169. doi: 10.1136/bmj-2023-077169.

Abstract

OBJECTIVE

To develop and externally validate a prediction model for severe cisplatin associated acute kidney injury (CP-AKI).

DESIGN

Multicenter cohort study.

SETTING

Six geographically diverse major academic cancer centers across the US.

PARTICIPANTS

Adults (≥18 years) receiving their first dose of intravenous cisplatin, 2006-22.

MAIN OUTCOME MEASURES

The primary outcome was CP-AKI, defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of intravenous cisplatin. Independent predictors of CP-AKI were identified using a multivariable logistic regression model, which was developed in a derivation cohort and tested in an external validation cohort. For the primary model, continuous variables were examined using restricted cubic splines. A simple risk model was also generated by converting the odds ratios from the primary model into risk points. Finally, a multivariable Cox model was used to examine the association between severity of CP-AKI and 90 day survival.

RESULTS

A total of 24 717 adults were included, with 11 766 in the derivation cohort (median age 59 (interquartile range (IQR) 50-67)) and 12 951 in the validation cohort (median age 60 (IQR 50-67)). The incidence of CP-AKI was 5.2% (608/11 766) in the derivation cohort and 3.3% (421/12 951) in the validation cohort. Each of the following factors were independently associated with CP-AKI in the derivation cohort: age, hypertension, diabetes mellitus, serum creatinine level, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose. A simple risk score consisting of nine covariates was shown to predict a higher risk of CP-AKI in a monotonic fashion in both the derivation cohort and the validation cohort. Compared with patients in the lowest risk category, those in the highest risk category showed a 24.00-fold (95% confidence interval (CI) 13.49-fold to 42.78-fold) higher odds of CP-AKI in the derivation cohort and a 17.87-fold (10.56-fold to 29.60-fold) higher odds in the validation cohort. The primary model had a C statistic of 0.75 and showed better discrimination for CP-AKI than previously published models, the C statistics for which ranged from 0.60 to 0.68 (DeLong P<0.001 for each comparison). Greater severity of CP-AKI was monotonically associated with shorter 90 day survival (adjusted hazard ratio 4.63 (95% CI 3.56 to 6.02) for stage 3 CP-AKI versus no CP-AKI).

CONCLUSION

This study found that a simple risk score based on readily available variables from patients receiving intravenous cisplatin could predict the risk of severe CP-AKI, the occurrence of which is strongly associated with death.

摘要

目的

开发和外部验证用于预测严重顺铂相关急性肾损伤(CP-AKI)的预测模型。

设计

多中心队列研究。

地点

美国六个地理位置不同的主要学术癌症中心。

参与者

接受第一次静脉内顺铂治疗的成年人(≥18 岁),2006-22 年。

主要结局测量

主要结局是 CP-AKI,定义为首次静脉内顺铂治疗后 14 天内血清肌酐增加两倍或以上或需要肾脏替代治疗。使用多变量逻辑回归模型确定 CP-AKI 的独立预测因素,该模型在推导队列中进行开发,并在外部验证队列中进行测试。对于主要模型,连续变量使用受限立方样条进行检查。还通过将主要模型中的优势比转换为风险点来生成简单的风险模型。最后,使用多变量 Cox 模型来检查 CP-AKI 严重程度与 90 天生存率之间的关联。

结果

共纳入 24717 名成年人,其中推导队列 11766 人(中位年龄 59 岁(四分位距(IQR)50-67)),验证队列 12951 人(中位年龄 60 岁(IQR 50-67))。CP-AKI 在推导队列中的发生率为 5.2%(608/11766),在验证队列中的发生率为 3.3%(421/12951)。在推导队列中,以下每个因素均与 CP-AKI 独立相关:年龄、高血压、糖尿病、血清肌酐水平、血红蛋白水平、白细胞计数、血小板计数、血清白蛋白水平、血清镁水平和顺铂剂量。简单的风险评分由九个协变量组成,在推导队列和验证队列中均呈单调递增趋势,提示 CP-AKI 的风险更高。与风险最低类别中的患者相比,风险最高类别中的患者 CP-AKI 的比值比(95%置信区间(CI)为 13.49 倍至 42.78 倍)和验证队列中比值比(95%CI 为 10.56 倍至 29.60 倍)均更高。主要模型的 C 统计量为 0.75,与先前发表的模型相比,对 CP-AKI 的判别能力更好,后者的 C 统计量范围为 0.60 至 0.68(每种比较的 DeLong P<0.001)。CP-AKI 严重程度的增加与 90 天生存率的缩短呈单调相关(CP-AKI 3 期与无 CP-AKI 相比,调整后的危险比为 4.63(95%CI 3.56 至 6.02))。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e60/10964715/f6e2ed18bec0/gups077169.f1.jpg

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