Prognostic implications of the arginine metabolism in patients at nutritional risk: A secondary analysis of the randomized EFFORT trial.

Franziska Stumpf, Peter Neyer, Luca Bernasconi, Stephan C Bischoff, Carla Wunderle, Pascal Tribolet, Beat Mueller, Philipp Schuetz, Zeno Stanga, Jacqueline Ritz

Journal: Clinical nutrition (Edinburgh, Scotland) 2024;43(3):660-673

PMID: 38309228

Full Text on Elsevier Science View on PubMed

Abstract

BACKGROUND

Arginine, a conditionally essential amino acid, is key component in metabolic pathways including immune regulation and protein synthesis. Depletion of arginine contributes to worse outcomes in severely ill and surgical patient populations. We assessed prognostic implications of arginine levels and its metabolites and ratios in polymorbid medical inpatients at nutritional risk regarding clinical outcomes and treatment response.

METHODS

Within this secondary analysis of the randomized controlled Effect of early nutritional support on Frailty, Functional Outcomes, and Recovery of malnourished medical inpatients Trial (EFFORT), we investigated the association of arginine, its metabolites and ratios (i.e., ADMA and SDMA, ratios of arginine/ADMA, arginine/ornithine, and global arginine bioavailability ratio) measured on hospital admission with short-term and long-term mortality by means of regression analysis.

RESULTS

Among the 231 patients with available measurements, low arginine levels ≤90.05 μmol/l (n = 86; 37 %) were associated with higher all-cause mortality at 30 days (primary endpoint, adjusted HR 3.27, 95 % CI 1.86 to 5.75, p < 0.001) and at 5 years (adjusted HR 1.50, 95 % CI 1.07 to 2.12, p = 0.020). Arginine metabolites and ratios were also associated with adverse outcome, but had lower prognostic value. There was, however, no evidence that treatment response was influenced by admission arginine levels.

CONCLUSION

This secondary analysis focusing on medical inpatients at nutritional risk confirms a strong association of low plasma arginine levels and worse clinical courses. The potential effects of arginine-enriched nutritional supplements should be investigated in this population of patients.

CLINICAL TRIAL REGISTRATION

clinicaltrials.gov as NCT02517476 (registered 7 August 2015).

Address: Medical University Department, Division of General Internal and Emergency Medicine, Kantonsspital Aarau, Tellstrasse 25, 5001 Aarau, Switzerland; Institute of Nutritional Medicine, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany.; Medical University Department, Division of General Internal and Emergency Medicine, Kantonsspital Aarau, Tellstrasse 25, 5001 Aarau, Switzerland.; Institute of Laboratory Medicine, Kantonsspital Aarau, Tellstrasse 25, 5001 Aarau, Switzerland.; Medical University Department, Division of General Internal and Emergency Medicine, Kantonsspital Aarau, Tellstrasse 25, 5001 Aarau, Switzerland; Department of Health Professions, Bern University of Applied Sciences, Falkenplatz 24, 3012 Bern, Switzerland; Faculty of Life Sciences University of Vienna, Djerassiplatz 1, 1030 Vienna, Austria.; Division of Diabetes, Endocrinology, Nutritional Medicine, and Metabolism, Bern University Hospital and University of Bern, Freiburgstrasse 15, 3010 Bern, Switzerland.; Medical University Department, Division of General Internal and Emergency Medicine, Kantonsspital Aarau, Tellstrasse 25, 5001 Aarau, Switzerland; Medical Faculty of the University of Basel, Klingelbergstrasse 61, 4056 Basel, Switzerland.; Institute of Nutritional Medicine, University of Hohenheim, Garbenstraße 30, 70599 Stuttgart, Germany.; Medical University Department, Division of General Internal and Emergency Medicine, Kantonsspital Aarau, Tellstrasse 25, 5001 Aarau, Switzerland; Medical Faculty of the University of Basel, Klingelbergstrasse 61, 4056 Basel, Switzerland. Electronic address: [email protected].

DOI: 10.1016/j.clnu.2024.01.012

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MeSH Terms: Humans, Prognosis, Inpatients, Arginine, Biological Availability, Amino Acids, Essential