儿童急性肾损伤临床亚表型的探索及其与预后的关系

Clinical sub-phenotypes of acute kidney injury in children and their association with prognosis

摘要:

目的 探索儿童急性肾损伤（acute kidney injury, AKI）临床亚表型（sub-phenotype, SP）的存在及其与临床结局的关系。方法 记录推导队列（n=650）和验证队列（n=177）AKI患儿入住儿科重症监护室（pediatric intensive care unit, PICU）首个24 h内的一般情况、实验室指标初始值。在推导队列中，运用最小绝对收缩和选择算子筛选与病死相关的指标并用于二阶聚类以寻找AKI临床SP。运用logistic回归简化分类模型，采用受试者操作特征曲线评估简化后模型价值，并应用于验证队列和推导+验证队列。以所有AKI患儿为研究对象，分析各SP与临床结局的关系。结果 在推导队列中将筛选出的20个变量用于二阶聚类识别出2个AKI临床SP（SP1、SP2），即SP_推1组（n=536）和SP_推2组（n=114）。包含8个指标（P<0.05）的简化分类模型鉴别2类AKI临床SP的曲线下面积为0.965（P<0.001）。验证队列聚类成SP_验1组（n=156）和SP_验2组（n=21），推导+验证队列聚类成SP1组（n=694）和SP2组（n=133）。校正混杂因素后，SP2组患儿入住PICU期间多器官功能障碍综合征的发生率及病死率显著高于SP1组（P<0.001）；SP2与PICU 28 d内的死亡风险显著相关（P<0.001）。结论 该研究建立了一个简单的分类模型并确定了2种具有不同临床特征及结局的AKI临床SP，其中SP2组患儿疾病严重程度更重，临床预后更差。

Abstract:

Objective To investigate the clinical sub-phenotype (SP) of pediatric acute kidney injury (AKI) and their association with clinical outcomes.Methods General status and initial values of laboratory markers within 24 hours after admission to the pediatric intensive care unit (PICU) were recorded for children with AKI in the derivation cohort (n=650) and the validation cohort (n=177). In the derivation cohort, a least absolute shrinkage and selection operator (LASSO) regression analysis was used to identify death-related indicators, and a two-step cluster analysis was employed to obtain the clinical SP of AKI. A logistic regression analysis was used to develop a parsimonious classifier model with simplified metrics, and the area under the curve (AUC) was used to assess the value of this model. This model was then applied to the validation cohort and the combined derivation and validation cohort. The association between SPs and clinical outcomes was analyzed with all children with AKI as subjects.Results In the derivation cohort, two clinical SPs of AKI (SP1 and SP2) were identified by the two-step cluster analysis using the 20 variables screened by LASSO regression, namely SP_d1 group (n=536) and SP_d2 group (n=114). The simplified classifier model containing eight variables (P<0.05) had an AUC of 0.965 in identifying the two clinical SPs of AKI (P<0.001). The validation cohort was clustered into SP_v1 group (n=156) and SP_v2 group (n=21), and the combined derivation and validation cohort was clustered into SP1 group (n=694) and SP2 group (n=133). After adjustment for confounding factors, compared with the SP1 group, the SP2 group had significantly higher incidence rates of multiple organ dysfunction syndrome and death during the PICU stay (P<0.001), and SP2 was significantly associated with the risk of death within 28 days after admission to the PICU (P<0.001).Conclusions This study establishes a parsimonious classifier model and identifies two clinical SPs of AKI with different clinical features and outcomes.The SP2 group has more severe disease and worse clinical prognosis.