Identification and validation of chronic critical illness subphenotypes using urea–creatinine ratio trajectories

IF 7.4 2区医学 Q1 NUTRITION & DIETETICS

Clinical nutrition Pub Date : 2025-08-22 DOI:10.1016/j.clnu.2025.08.023

Wanting Su , Zhigang Cui , Jinhe Sun , He Miao , Qianhui Chen , Yuzhong Zhang , Shubo Zhang , Zhihua Yin , Renyu Ding

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引用次数: 0

Abstract

Background & aims

Chronic critical illness (CCI) is common in intensive care units (ICUs) and is highly heterogeneous. We utilized urea–creatinine ratio (UCR) trajectories to develop and validate subphenotypes and reveal the heterogeneous treatment effects of medical nutrition therapy.

Methods

This retrospective study included all CCI patients from three public critical care databases. Group-based trajectory modeling (GBTM) was applied to the UCR for subphenotype development and validation. A multivariate Cox regression model was used to assess the independent associations of these subphenotypes with mortality. Generalized estimation equations were used to reveal the potential heterogeneity in medical nutrition therapy between survivors and nonsurvivors in different subphenotypes.

Results

A total of 4047 CCI patients were divided into three subphenotypes on the basis of their UCR trajectories. Stable low subphenotype had a low UCR with a slight upwards trend, the youngest age, and the fewest comorbidities. Intermediate subphenotype was characterized by a medium UCR. Stable high subphenotype had a high UCR with a rapid increase and the highest ICU mortality (14.72 %), hospital mortality (36.20 %) and 28-day mortality (39.26 %) (p < 0.05). In the multivariate Cox regression with Stable low subphenotype as control, Stable high subphenotype had increased risks of hospitalization mortality (HR: 2.74; 95 % CI: 2.01–3.72; P < 0.001), 28-day mortality (HR: 3.20; 95 % CI: 2.36–4.34; P < 0.001) and ICU mortality (HR: 2.78; 95 % CI: 1.71–4.52; P < 0.001). In CCI patients, the dose of nutritional intake within 5 days after CCI diagnosis were greater in the survival group (P < 0.05), especially survivors in Intermediate and Stable high subphenotypes.

Conclusion

We demonstrated that longitudinal UCR trajectories during the first 10 days of ICU admission serve as robust biomarkers for predicting CCI into three distinct subphenotypes to understand patient heterogeneity. For CCI patients, higher doses of enteral nutrition and protein intake after CCI diagnosis may improve prognosis, especially for patients in the subphenotypes with the higher baseline UCR values showing an upward trend and poorer prognosis. A prospective study is needed to validate these findings, inform practice and guide future research on personalized care.

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使用尿素-肌酐比值轨迹识别和验证慢性危重疾病亚表型

背景目的慢性危重症（CCI）常见于重症监护病房（icu），且具有高度异质性。我们利用尿素-肌酐比值（UCR）轨迹来发展和验证亚表型，并揭示医学营养治疗的异质性治疗效果。方法回顾性研究纳入来自3个公共重症监护数据库的所有CCI患者。基于群体的轨迹建模（GBTM）应用于UCR进行亚表型的发展和验证。使用多变量Cox回归模型来评估这些亚表型与死亡率的独立关联。使用广义估计方程来揭示不同亚表型的幸存者和非幸存者之间医疗营养治疗的潜在异质性。结果4047例CCI患者根据其UCR轨迹可分为3个亚表型。稳定低亚表型的UCR低且有轻微上升趋势，年龄最小，合并症最少。中间亚表型以中等UCR为特征。稳定高亚表型患者UCR高且上升迅速，ICU病死率最高（14.72%），住院病死率最高（36.20%），28天病死率最高（39.26%）（p < 0.05）。在以稳定低亚表型为对照的多因素Cox回归中，稳定高亚表型患者住院死亡率（HR: 2.74; 95% CI: 2.01-3.72; P < 0.001）、28天死亡率（HR: 3.20; 95% CI: 2.36-4.34; P < 0.001）和ICU死亡率（HR: 2.78; 95% CI: 1.71-4.52; P < 0.001）的风险增加。在CCI患者中，生存组在CCI诊断后5天内的营养摄入剂量更大（P < 0.05），特别是中高亚表型和稳定高亚表型的幸存者。我们证明了ICU入院前10天的纵向UCR轨迹可以作为预测CCI分为三种不同亚表型的强有力的生物标志物，以了解患者的异质性。对于CCI患者，CCI诊断后高剂量的肠内营养和蛋白质摄入可能改善预后，特别是基线UCR值较高的亚表型患者呈上升趋势，预后较差。需要一项前瞻性研究来验证这些发现，为实践提供信息并指导未来个性化护理的研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical nutrition 医学-营养学

CiteScore

14.10

自引率

6.30%

发文量

356

审稿时长

28 days

期刊介绍： Clinical Nutrition, the official journal of ESPEN, The European Society for Clinical Nutrition and Metabolism, is an international journal providing essential scientific information on nutritional and metabolic care and the relationship between nutrition and disease both in the setting of basic science and clinical practice. Published bi-monthly, each issue combines original articles and reviews providing an invaluable reference for any specialist concerned with these fields.