# Association between Endothelial Activation and Stress Index and mortality in diabetic nephropathy ICU patients: A retrospective cohort study

**Authors:** Sheng Chen, Lin Guo, Xiaohan Ma, Shuaikang Wang, Junchao Wu, Lingling Wu, Ting Zhang, Hongjun Gao

PMC · DOI: 10.1371/journal.pone.0329233 · PLOS One · 2025-08-14

## TL;DR

Higher EASIX scores are linked to increased short-term mortality in critically ill diabetic nephropathy patients, suggesting it could help predict outcomes and guide treatment.

## Contribution

This study is the first to show EASIX as an independent predictor of mortality in diabetic nephropathy ICU patients.

## Key findings

- Higher EASIX scores correlated with increased ICU and in-hospital mortality rates.
- EASIX remained an independent predictor of mortality after adjusting for age, sex, and comorbidities.
- Subgroup analysis confirmed EASIX's association with mortality in older patients and those with severe complications.

## Abstract

Diabetic nephropathy (DN) is a serious complication of diabetes mellitus, often leading to poor outcomes in critically ill patients. Endothelial Activation and Stress Index (EASIX), a marker of endothelial dysfunction and systemic stress, has been associated with adverse outcomes in various diseases, but its role in predicting mortality in DN patients remains unclear.

A retrospective cohort study was conducted using the MIMIC-IV database. A total of 1,260 critically ill DN patients were included and stratified into tertiles based on their EASIX scores. Kaplan-Meier survival analysis, Cox proportional hazard models, and restricted cubic spline regression were applied to evaluate the association between EASIX and 30- and 60-day all-cause mortality. Subgroup analyses were also performed to assess interactions with key patient characteristics.

Patients with higher EASIX scores had significantly increased ICU and in-hospital mortality rates. Cox regression analyses revealed that EASIX was an independent predictor of mortality after adjusting for age, sex, and comorbidities (HR: 1.14; 95% CI: 1.03–1.26; p = 0.01). Kaplan-Meier analysis showed significantly worse survival rates in the highest EASIX tertile. Subgroup analysis showed that higher EASIX scores were still associated with short-term survival in patients with DN in the presence of older age, male gender, and severe complications.

Higher EASIX scores are associated with increased short-term mortality in critically ill DN patients, highlighting its value as a prognostic biomarker for risk stratification and personalized management. Further studies are needed to validate these findings and explore therapeutic interventions targeting endothelial dysfunction.

## Linked entities

- **Diseases:** diabetic nephropathy (MONDO:0005016), diabetes mellitus (MONDO:0005015)

## Full-text entities

- **Genes:** ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, SH2B2 (SH2B adaptor protein 2) [NCBI Gene 10603] {aka APS}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, VCAM1 (vascular cell adhesion molecule 1) [NCBI Gene 7412] {aka CD106, INCAM-100}
- **Diseases:** ill (MESH:D002908), consumptive coagulopathy (MESH:D004211), cardiovascular disease (MESH:D002318), release (MESH:C566759), renal function (MESH:D058186), necrosis (MESH:D009336), traumatic brain injury (MESH:D000070642), end-stage renal disease (MESH:D007676), EASIX (MESH:D000079225), atherosclerosis (MESH:D050197), RF (MESH:C538347), Death (MESH:D003643), Inflammation (MESH:D007249), albuminuria (MESH:D000419), coma (MESH:D003128), critically ill (MESH:D016638), Endothelial (MESH:D005642), Stroke (MESH:D020521), tubulointerstitial fibrosis (MESH:D005355), TIA (MESH:D002546), Sepsis (MESH:D018805), Organ Failure (MESH:D009102), septic (MESH:D001170), kidney damage (MESH:D007674), Atrial fibrillation (MESH:D001281), infection (MESH:D007239), Arterial fibrillation (MESH:D014693), diabetes mellitus (MESH:D003920), DN (MESH:D003928), hypertension (MESH:D006973), hyperglycemia (MESH:D006943), glomerulosclerosis (MESH:D005921), COVID-19 (MESH:D000086382), Heart failure (MESH:D006333), Paraplegia (MESH:D010264), Endothelial dysfunction (MESH:D014652), Respiratory failure (MESH:D012131)
- **Chemicals:** glucose (MESH:D005947), ROS (MESH:D017382), malondialdehyde (MESH:D008315), FBG (-), nitric oxide (MESH:D009569), lipid (MESH:D008055), creatinine (MESH:D003404), reactive nitrogen species (MESH:D026361), Sodium (MESH:D012964)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

36 references — full list in the complete paper: https://tomesphere.com/paper/PMC12352680/full.md

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Source: https://tomesphere.com/paper/PMC12352680