Early Enteral Nutrition and Sepsis-Associated Acute Kidney Injury: A Propensity Score Matched Cohort Study Based on the MIMIC-III Database

Yonsei Medical Journal · 10 authors, 1 centre

AI SUMMARY

FIDELITY 100%

POPULATION2364 adult septic patients from the MIMIC-III database who received enteral nutrition during their first ICU admission (median age 66.32 years, 56.6% male).

INTERVENTIONEarly enteral nutrition (EEN) initiated within 53 hours of ICU admission (optimal cut-off determined by ROC curve analysis).

COMPARISONDelayed enteral nutrition (DEN) initiated after 53 hours of ICU admission.

This summary was generated by AI from a single paper. It has not been reviewed by a clinician and is not clinical advice. Verify against the source before acting on it.

AGENT 01 · STRUCTURED SUMMARY

TRACE TO SOURCE

“

TL;DR

This retrospective cohort study using the MIMIC-III database found that early enteral nutrition (EEN) initiated within 53 hours of ICU admission was associated with a significantly reduced risk of sepsis-associated acute kidney injury (SA-AKI) (OR 0.319, 95% CI 0.245–0.413, p<0.001). EEN patients received less intravenous fluid (3750 mL vs. 5513.23 mL, p<0.001), and causal mediation analysis suggested that 20.54% of the beneficial effect of EEN on AKI was mediated by reduced IVF volume. These findings support early initiation of enteral nutrition in septic patients as a strategy to potentially reduce AKI incidence and severity.

Full summary

3,436 CHARS

**Background:** Sepsis-associated acute kidney injury (SA-AKI) is a severe complication of sepsis, affecting 40–50% of AKI cases in the ICU and approximately 60% of septic patients, with mortality ranging from 38.2% to 70.2%. Early enteral nutrition (EEN) is recommended in sepsis guidelines for its benefits in maintaining gut integrity and reducing inflammation, but its association with AKI incidence had not been well studied. Additionally, the optimal timing of EEN had not been statistically determined.

**Methods:** This retrospective cohort study used the MIMIC-III database, which includes over 60,000 ICU admissions from Beth Israel Deaconess Medical Center (2001–2012). Patients over 18 years with sepsis (diagnosed via Angus methodology) who received enteral nutrition during their first ICU stay were included; those with ICU stays <24 hours were excluded. Among 61,532 admissions, 17,420 had sepsis, and 2,364 met all inclusion criteria. Receiver operating characteristic (ROC) curve analysis with AKI as the outcome variable determined the optimal cut-off time for EEN. Propensity score matching (PSM) with 1:1 nearest neighbor matching (caliper 0.05) was used to control confounding. Logistic regression, inverse probability of treatment weighting (IPTW), and causal mediation analysis (CMA) were performed. AKI was diagnosed per KDIGO criteria.

**Key Results:** ROC analysis identified 53.331 hours after ICU admission as the optimal EEN cut-off (sensitivity 0.5467, specificity 0.7673, AUC 0.7005, Youden index 0.3141). Of 2,364 patients, 1,212 were assigned to EEN (≤53 hours) and 1,152 to DEN (>53 hours). The overall AKI incidence was 80.5%. After PSM, EEN was associated with significantly lower AKI risk (OR 0.204, 95% CI 0.097–0.429, p<0.001), consistent with logistic regression (OR 0.319, 95% CI 0.245–0.413, p<0.001) and IPTW (OR 0.393, 95% CI 0.337–0.458, p<0.001). AKI incidence was 74.2% in EEN vs. 88.4% in DEN (p<0.001). EEN patients had more stage 1 AKI (15% vs. 12.1%) and less stage 3 AKI (29% vs. 42.4%, p<0.001). EEN patients received less IVF (3750 mL vs. 5513.23 mL, p<0.001), had shorter ICU stays (7.54 vs. 11.67 days, p<0.001) and hospital stays (13.85 vs. 18.03 days, p<0.001), and more ventilator-free days (23.87 vs. 21.33, p<0.001), vasopressor-free days (27.92 vs. 27.2, p<0.001), and CRRT-free days (27.73 vs. 27.2, p<0.001). 28-day mortality did not differ significantly. CMA showed that IVF volume mediated 20.54% (95% CI 11.74–32, p<0.001) of EEN's beneficial effect on AKI. Within the EEN group, no significant differences in AKI outcomes were found between 0–48h and 48–53h subgroups, except shorter ICU and hospital stays with earlier initiation.

**Clinical Implications:** This study provides evidence that early enteral nutrition (within 53 hours of ICU admission) is associated with reduced incidence and severity of SA-AKI in septic patients, with the effect partially mediated by reduced intravenous fluid requirements. The findings support current guidelines recommending early EN initiation in sepsis and suggest a potential mechanism through fluid volume management. However, as a single-center retrospective study, the optimal timing of 53 hours should not be interpreted as a precise clinical threshold without further prospective validation. Limitations include missing data on EN composition, rate, and CVP values, and the inability to establish definitive causality.

PICO

PPOPULATION

2364 adult septic patients from the MIMIC-III database who received enteral nutrition during their first ICU admission (median age 66.32 years, 56.6% male).

IINTERVENTION

Early enteral nutrition (EEN) initiated within 53 hours of ICU admission (optimal cut-off determined by ROC curve analysis).

OOUTCOME

Primary: incidence of AKI. Secondary: AKI stages, 28-day mortality, length of ICU and hospital stay, ventilator-/CRRT-/vasopressor-free days, and volume of intravenous fluid during ICU stay.

STUDY TYPE

cohort

SPECIALTY

critical care

SUMMARISED BY

AI pipeline

FIDELITY CHECK

100% · A

ORIGINAL PAPER

PMC10067798

Early Enteral Nutrition and Sepsis-Associated Acute Kidney Injury: A Propensity Score Matched Cohort Study Based on the MIMIC-III Database

Yonsei Medical Journal

READ THE FULL PAPER

ABSTRACT

Purpose We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.) Materials and Methods The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. Results 2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245–0.413, p <0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p <0.001). The mediating effect of IVF was significant ( p <0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0–48 hours vs. 48–53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. Conclusion EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.

CITATION EXPORT

Jun Wang, Li Jiang, Sheng Ding et al.. Early Enteral Nutrition and Sepsis-Associated Acute Kidney Injury: A Propensity Score Matched Cohort Study Based on the MIMIC-III Database. Yonsei Medical Journal. (2023). https://doi.org/10.3349/ymj.2022.0276

AUTHORS

10 · 1 CENTRES

Jun Wang, Li Jiang, Sheng Ding, Si-Yi He, Shun-Bi Liu, Zhong-Jie Lu, Yuan-Zhang Liu, Li-Wen Hou, Bin-Su Wang, Jin-Bao Zhang

Department of Cardiovascular Surgery, People’s Liberation Army The General Hospital of Western Theater Command, Chengdu, Sichuan, China.