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.

中文翻译：

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用于预测静脉注射顺铂后严重急性肾损伤的简单风险评分的推导和外部验证：队列研究

目的 开发并外部验证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。在美国设立六个不同地理位置的主要学术癌症中心。参与者 2006 年 22 月接受第一剂静脉注射顺铂的成人（≥18 岁）。主要结局指标 主要结局指标为 CP-AKI，定义为首次静脉注射顺铂后 14 天内血清肌酐或肾脏替代治疗增加两倍或以上。使用多变量逻辑回归模型确定了 CP-AKI 的独立预测因子，该模型在推导队列中开发并在外部验证队列中进行测试。对于主要模型，使用受限三次样条检查连续变量。通过将主要模型的比值比转换为风险点，还生成了一个简单的风险模型。最后，使用多变量 Cox 模型检查 CP-AKI 严重程度与 90 天生存率之间的关联。结果 总共纳入了 24 717 名成年人，其中推导队列中有 11 766 名成年人（中位年龄 59 岁（四分位距 (IQR) 50-67）），验证队列中有 12 951 名成年人（中位年龄 60 岁（IQR 50-67）） 。推导队列中 CP-AKI 的发生率为 5.2% (608/11 766)，验证队列中 CP-AKI 的发生率为 3.3% (421/12 951)。在衍生队列中，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。在推导队列和验证队列中，由 9 个协变量组成的简单风险评分可以以单调方式预测 CP-AKI 的较高风险。与最低风险类别的患者相比，最高风险类别的患者在衍生队列中出现 CP-AKI 的几率高 24.00 倍（95% 置信区间 (CI) 13.49 倍至 42.78 倍），并且 17.87 倍。验证队列中的几率高出 10.56 倍至 29.60 倍。主要模型的 C 统计量为 0.75，并且比之前发布的模型表现出更好的 CP-AKI 辨别能力，其 C 统计量范围为 0.60 至 0.68（每次比较的 DeLong P<0.001）。更严重的 CP-AKI 与更短的 90 天生存率单调相关（3 期 CP-AKI 与无 CP-AKI 相比，调整后的风险比为 4.63（95% CI 3.56 至 6.02））。结论 这项研究发现，基于接受静脉注射顺铂的患者的现成变量进行的简单风险评分可以预测严重 CP-AKI 的风险，而严重 CP-AKI 的发生与死亡密切相关。