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Research Article | Open Access

Early protein delivery in critically ill patients with acute kidney injury: post hoc analysis of a multicenter cluster-randomized controlled trial

Cheng Lv1,†, Lingliang Zhou2,†, Yufeng Zhou3, Charles Chin Han Lew4, Zheng-Yii Lee5,6, M. Shahnaz Hasan6,7, Baiqiang Li1,8,9, Yang Liu2, Jiajia Lin1, Wenjian Mao1, Christian Stoppe5,10, Arthur Raymond Hubert van Zanten11,12, Weiqin Li1,8,9, Yuxiu Liu3,8,9( ), Lu Ke1,8,9 ( )
Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, 22 Hankou Road, Gulou District, Nanjing 210093, China
Department of Critical Care Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Southeast University, 87 Ding Jiaqiao, Gulou District, Nanjing 210009, China
Department of Biostatistics, School of Public Health, Southern Medical University, 1023-1063 Shatai South Road, Baiyun District, Guangzhou 510515, China
Department of Dietetics and Nutrition, Ng Teng Fong General Hospital, Singapore, Singapore 1 Jurong East Street 21, Singapore
Department of Cardiac Anesthesiology and Intensive Care Medicine, Charité Berlin, Charitéplatz 1, 10117 Berlin, Germany
Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur 50603, Malaysia
Department of Anaesthesiology, Universiti Malaya Medical Centre, Lembah Pantai, Kuala Lumpur 59100, Malaysia
National Institute of Healthcare Data Science, Nanjing University, 22 Hankou Road, Gulou District, Nanjing 210093, China
Research Institute of Critical Care Medicine and Emergency Rescue At Nanjing University, 22 Hankou Road, Gulou District, Nanjing 210093, Jiangsu Province, China
Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, University Hospital Würzburg, Oberdürrbacher Str. 6, 97080, Würzburg, Germany
Department of Intensive Care, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP Ede, The Netherlands
Division of Human Nutrition and Health, Wageningen University & Research, Helix (Building 124), Stippeneng 4, 6708 WE Wageningen, The Netherlands

†Cheng Lv and Lingliang Zhou contributed equally to this work.

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Highlights

• By analyzing data from a multicenter cluster-randomised controlled trial (n = 2772), we provide insights into optimal early protein delivery in critically ill patients with various AKI stages.

• Overall, in critically ill patients, increased early protein delivery (up to close to the guideline recommendation) was significantly associated with a reduction in 28-day mortality.

• Early protein delivery and 28-day mortality significantly interacted with baseline AKI stages. Increased early protein delivery was only associated with reduced 28-day mortality in patients without AKI and with AKI stage Ⅲ, but not in those with AKI stage Ⅰ or Ⅱ.

• More high-quality evidence is needed to evaluate the role of renal function in protein delivery in critically ill patients.

Abstract

Background

There is controversy over the optimal early protein delivery in critically ill patients with acute kidney injury (AKI). This study aims to evaluate whether the association between early protein delivery and 28-day mortality was impacted by the presence of AKI in critically ill patients.

Methods

This is a post hoc analysis of data from a multicenter cluster-randomised controlled trial enrolling newly admitted critically ill patients (n = 2772). Participants without chronic kidney disease and with complete data concerning baseline renal function were included in this study. The primary outcome was 28-day mortality. Cox proportional hazards models were used to analyze the association between early protein delivery, reflected by mean protein delivery from day 3–5 after enrollment, 28-day mortality and whether baseline AKI stages interacted with this association.

Results

Overall, 2552 patients were included, among whom 567 (22.2%) had AKI at enrollment (111 stage Ⅰ, 87 stage Ⅱ, 369 stage Ⅲ). Mean early protein delivery was 0.60 ± 0.38 g/kg/day among the study patients. In the overall study cohort, each 0.1 g/kg/day increase in protein delivery was associated with a 5% reduction in 28-day mortality[hazard ratio (HR) = 0.95; 95% confidence interval (CI) 0.92–0.98, p < 0.001]. The association between early protein delivery and 28-day mortality significantly interacted with baseline AKI stages (adjusted interaction p = 0.028). Each 0.1 g/kg/day increase in early protein delivery was associated with a 4% reduction in 28-day mortality (HR = 0.96; 95%CI 0.92–0.99, p = 0.011) among patients without AKI and 9% (HR = 0.91; 95%CI 0.84–0.99, p = 0.021) among those with AKI stage Ⅲ. However, such associations cannot be observed among patients with AKI stages Ⅰ and Ⅱ.

Conclusions

Increased early protein delivery (up to close to the guideline recommendation) was associated with reduced 28-day mortality in critically ill patients without AKI and with AKI stage Ⅲ, but not in those with AKI stage Ⅰ or Ⅱ.

Keywords

Protein deliveryMortalityAcute kidney injuryRenal replacement therapyCritical illness

References

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Burns & Trauma
Volume 12,
December 2024
Article number: tkae027
DOI: 10.1093/burnst/tkae027

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Cite this article:
Lv C, Zhou L, Zhou Y, et al. Early protein delivery in critically ill patients with acute kidney injury: post hoc analysis of a multicenter cluster-randomized controlled trial. Burns & Trauma, 2024, 12: tkae027. https://doi.org/10.1093/burnst/tkae027

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Received: 10 January 2024
Revised: 05 March 2024
Accepted: 30 April 2024
Published: 10 October 2026
© The Author(s) 2024. Published by Oxford University Press.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.