The impact of higher protein dosing on outcomes in critically ill patients with acute kidney injury: a post hoc analysis of the EFFORT protein trial

Stoppe C 1 , Patel JJ 2 , Zarbock A 3 , Lee ZY 4 , Rice TW 5 , Mafrici B 6 Show all authors , Wehner R 7 , Chan MHM 8 , Lai PCK 8 , MacEachern K 9 , Myrianthefs P 10 , Tsigou E 10 , Ortiz-Reyes L 11 , Jiang X 11 , Day AG 12 , Hasan MS 13 , Meybohm P 14 , Ke L 15 , Heyland DK 16

Affiliations 

  • 1 University Hospital Würzburg, Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Oberdürrbacher Str. 6, 97080, Würzburg, Germany. christian.stoppe@gmail.com
  • 2 Division of Pulmonary and Critical Care Medicine, Medical College of Wisconsin, Milwaukee, WI, USA
  • 3 Department of Anaesthesiology and Intensive Care Medicine, University of Münster, Münster, Germany
  • 4 Department of Cardiac Anesthesiology and Intensive Care Medicine, Charité Berlin, Berlin, Germany
  • 5 Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
  • 6 Renal and Transplantation Unit, Department of Dietetics and Nutrition, Nottingham University Hospitals NHS Trust, City Campus, Nottingham, UK
  • 7 Department of Clinical Nutrition, The Ohio State University Wexner Medical Center, Columbus, OH, USA
  • 8 Department of Adult Intensive Care, Queen Mary Hospital, Hong Kong, China
  • 9 Intensive Care Unit, Mount Sinai Hospital, Sinai Health System, Toronto, Canada
  • 10 Intensive Care Unit, Agioi Anargiroi Hospital, Athens, Greece
  • 11 Clinical Evaluation Research Unit, Queen's University, Watkins 5, Kingston General Hospital, Kingston, ON, K7L 2V7, Canada
  • 12 Department of Critical Care Medicine, Queen's University, Watkins 5, Kingston General Hospital, Kingston, ON, K7L 2V7, Canada
  • 13 Department of Anaesthesiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
  • 14 University Hospital Würzburg, Department of Anaesthesiology, Intensive Care, Emergency and Pain Medicine, Oberdürrbacher Str. 6, 97080, Würzburg, Germany
  • 15 Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, China
  • 16 Clinical Evaluation Research Unit, Queen's University, Watkins 5, Kingston General Hospital, Kingston, ON, K7L 2V7, Canada. dkh2@queensu.ca
Crit Care, 2023 Oct 18;27(1):399.
PMID: 37853490 DOI: 10.1186/s13054-023-04663-8

Abstract

BACKGROUND: Based on low-quality evidence, current nutrition guidelines recommend the delivery of high-dose protein in critically ill patients. The EFFORT Protein trial showed that higher protein dose is not associated with improved outcomes, whereas the effects in critically ill patients who developed acute kidney injury (AKI) need further evaluation. The overall aim is to evaluate the effects of high-dose protein in critically ill patients who developed different stages of AKI.

METHODS: In this post hoc analysis of the EFFORT Protein trial, we investigated the effect of high versus usual protein dose (≥ 2.2 vs. ≤ 1.2 g/kg body weight/day) on time-to-discharge alive from the hospital (TTDA) and 60-day mortality and in different subgroups in critically ill patients with AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria within 7 days of ICU admission. The associations of protein dose with incidence and duration of kidney replacement therapy (KRT) were also investigated.

RESULTS: Of the 1329 randomized patients, 312 developed AKI and were included in this analysis (163 in the high and 149 in the usual protein dose group). High protein was associated with a slower time-to-discharge alive from the hospital (TTDA) (hazard ratio 0.5, 95% CI 0.4-0.8) and higher 60-day mortality (relative risk 1.4 (95% CI 1.1-1.8). Effect modification was not statistically significant for any subgroup, and no subgroups suggested a beneficial effect of higher protein, although the harmful effect of higher protein target appeared to disappear in patients who received kidney replacement therapy (KRT). Protein dose was not significantly associated with the incidence of AKI and KRT or duration of KRT.

CONCLUSIONS: In critically ill patients with AKI, high protein may be associated with worse outcomes in all AKI stages. Recommendation of higher protein dosing in AKI patients should be carefully re-evaluated to avoid potential harmful effects especially in patients who were not treated with KRT.

TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT03160547) on May 17th 2017.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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