Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial
Abstract
Importance Acute kidney injury (AKI) is characterized by severe loss of glomerular filtration rate (GFR) and is associated with a prolonged intensive care unit (ICU) stay and increased risk of death. No interventions have yet been shown to prevent AKI or preserve GFR in critically ill patients. Evidence from mammalian physiology and small clinical trials suggests higher amino acid intake may protect the kidney from ischemic insults and thus may preserve GFR during critical illness. Objective To determine whether amino acid therapy, achieved through daily intravenous (IV) supplementation with standard amino acids, preserves kidney function in critically ill patients. Design, setting, and participants Multicenter, phase II, randomized clinical trial conducted between December 2010 and February 2013 in the ICUs of 16 community and tertiary hospitals in Australia and New Zealand. Participants were adult critically ill patients expected to remain in the study ICU for longer than 2 days. Interventions Random allocation to receive a daily supplement of up to 100 g of IV amino acids or standard care. Main outcomes and measures Duration of renal dysfunction (primary outcome); estimated GFR (eGFR) derived from creatinine; eGFR derived from cystatin C; urinary output; renal replacement therapy (RRT) use; fluid balance and other measures of renal function. Results 474 patients were enrolled and randomized (235 to standard care, 239 to IV amino acid therapy). At time of enrollment, patients allocated to receive amino acid therapy had higher APACHE II scores (20.2 ± 6.8 vs. 21.7 ± 7.6, P = 0.02) and more patients had pre-existing renal dysfunction (29/235 vs. 44/239, P = 0.07). Duration of renal dysfunction after enrollment did not differ between groups (mean difference 0.21 AKI days per 10 patient ICU days, 95 % CI -0.27 to 1.04, P = 0.45). Amino acid therapy significantly improved eGFR (treatment group × time interaction, P = 0.004), with an early peak difference of 7.7 mL/min/1.73 m(2) (95 % CI 1.0-14.5 mL/min/1.73 m(2), P = 0.02) on study day 4. Daily urine output was also significantly increased (+300 mL/day, 95 % CI 145-455 mL, P = 0.0002). There was a trend towards increased RRT use in patients receiving amino acid therapy (13/235 vs. 25/239, P = 0.062); however, this trend was not present after controlling for baseline imbalance (P = 0.21). Conclusion and relevance Treatment with a daily IV supplement of standard amino acids did not alter our primary outcome, duration of renal dysfunction. Trial registration anzctr.org.au Identifier: ACTRN12609001015235.
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Looijaard et al. showed that sarcopenic ICU patients benefit more from protein intake >1.2 g/kg per day.
“Looijaard et al. (168) showed that sarcopenic ICU patients benefit more from protein intake > 1.2 g/kg per day.”
From ESPEN guideline on clinical nutrition in the intensive care unit. (2019) · cites this paper as [168]
Cites
(1992) · PubMed · Cited by 33,716 · see citing works
The MOS 36-ltem Short-Form Health Survey (SF-36): I. Conceptual Framework and Item Selection
Ware, J. E., & Sherbourne, C. D. (1992) · Medical Care · doi:10.1097/00005650-199206000-00002 · Cited by 30,033 · see citing works
Toprak, Ö., Kurt, H., Sarı, Y., Şarkış, C., Us, H., & Kırık, A. (2017) · Kidney & Blood Pressure Research · doi:10.1159/000468530 · Cited by 29,769 · see citing works
A New Equation to Estimate Glomerular Filtration Rate
Levey, A. S., Stevens, L. A., Schmid, C. H., Zhang, Y. (., Castro, A. F., Feldman, H. I., Kusek, J. W., Eggers, P., Van Lente, F., Greene, T., et al. (2009) · Annals of Internal Medicine · doi:10.7326/0003-4819-150-9-200905050-00006 · Cited by 25,603 · see citing works
Knaus, W. A., Draper, E. A., Wagner, D. P., & Zimmerman, J. E. (1985) · Critical Care Medicine · doi:10.1097/00003246-198510000-00009 · Cited by 15,333 · see citing works
APACHE II-A Severity of Disease Classification System
Knaus, W. A., Draper, E. A., Wagner, D. P., & Zimmerman, J. E. (1986) · Critical Care Medicine · doi:10.1097/00003246-198608000-00028 · Cited by 13,379 · see citing works
Peto, R., Pike, M. C., Armitage, P., Breslow, N. E., Cox, D. R., Howard, S. V., Mantel, N., McPherson, K., Peto, J., & Smith, P. G. (1977) · British Journal of Cancer · doi:10.1038/bjc.1977.1 · Cited by 8,285 · see citing works
Bellomo, R., Ronco, C., Kellum, J. A., Mehta, R. L., Palevsky, P. M., & workgroup, T. A. (2004) · Critical Care · doi:10.1186/cc2872 · Cited by 6,769 · see citing works
Self-citationAPACHE II: a severity of disease classification system.
Knaus, W. A., Draper, E. S., Wagner, D. P., & Zimmerman, J. E. (1985) · PubMed · Cited by 6,034 · see citing works
Rosa, S. D., Samoni, S., Villa, G., & Ronco, C. (2017) · Blood Purification · doi:10.1159/000452650 · Cited by 5,037 · see citing works
Acute Renal Failure in Critically Ill Patients A Multinational, Multicenter Study
Uchino, S. (2005) · JAMA · doi:10.1001/jama.294.7.813 · Cited by 4,183 · see citing works
Comparison of Two Fluid-Management Strategies in Acute Lung Injury
(2006) · New England Journal of Medicine · doi:10.1056/nejmoa062200 · Cited by 3,538 · see citing works
A Comparison of Albumin and Saline for Fluid Resuscitation in the Intensive Care Unit
The SAFE Study Investigators (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040232 · Cited by 2,827 · see citing works
Peto, R., Pike, M. C., Armitage, P., Breslow, N. E., Cox, D. R., Howard, S. V., Mantel, N., McPherson, K., Peto, J., & Smith, P. G. (1976) · British Journal of Cancer · doi:10.1038/bjc.1976.220 · Cited by 2,294 · see citing works
Intensity of Continuous Renal-Replacement Therapy in Critically Ill Patients
The RENAL Replacement Therapy Study Investigators (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0902413 · Cited by 1,475 · see citing works
Zubrod, C. G., Schneiderman, M. A., Frei, E., Brindley, C. O., Gold, G. L., Shnider, B. I., Oviedo, R., Gorman, J. G., Jones, R., Jonsson, U., et al. (1960) · Journal of Chronic Diseases · doi:10.1016/0021-9681(60)90137-5 · Cited by 1,034 · see citing works
Stevens, L. A., Coresh, J., Schmid, C. H., Feldman, H. I., Froissart, M., Kusek, J. W., Rossert, J., Lente, F. V., Bruce, R. D., Zhang, Y., et al. (2008) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2007.11.018 · Cited by 1,031 · see citing works
Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial
Bellomo, R., Chapman, M. J., Finfer, S. R., Hickling, K. G., & Myburgh, J. (2000) · The Lancet · doi:10.1016/s0140-6736(00)03495-4 · Cited by 987 · see citing works
Self-citationAllocation concealment in randomised trials: defending against deciphering
Schulz, K. F., & Grimes, D. A. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07750-4 · Cited by 923 · see citing works
Acute kidney injury-epidemiology, outcomes and economics
Rewa, O., & Bagshaw, S. M. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2013.282 · Cited by 734 · see citing works
Early acute kidney injury and sepsis: a multicentre evaluation
Bagshaw, S. M., George, C., & Bellomo, R. (2008) · Critical Care · doi:10.1186/cc6863 · Cited by 700 · see citing works
Self-citationRepeated assessment of results in clinical trials of cancer treatment
Haybittle, J. L. (1971) · British Journal of Radiology · doi:10.1259/0007-1285-44-526-793 · Cited by 519 · see citing works
Bagshaw, S. M., George, C., Dinu, I. A., & Bellomo, R. (2007) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfm744 · Cited by 492 · see citing works
Self-citationAbel, R. M., Beck, C. H., Abbott, W. M., Ryan, J. A., Barnett, G. O., & Fischer, J. E. (1973) · New England Journal of Medicine · doi:10.1056/nejm197304052881401 · Cited by 471 · see citing works
Renal Functional Reserve and Renal Recovery after Acute Kidney Injury
Sharma, A., Mucino, M. J., & Ronco, C. (2014) · Nephron Clinical Practice · doi:10.1159/000363721 · Cited by 298 · see citing works
Bove, T., Zangrillo, A., Guarracino, F., Alvaro, G., Persi, B., Maglioni, E., Galdieri, N., Comis, M., Caramelli, F., Pasero, D., et al. (2014) · JAMA · doi:10.1001/jama.2014.13573 · Cited by 181 · see citing works
Self-citationMechanisms of renal hemodynamic regulation in response to protein feeding
Woods, L. L. (1993) · Kidney International · doi:10.1038/ki.1993.299 · Cited by 150 · see citing works
Comparison of different equations to assess glomerular filtration in critically ill patients
Carlier, M., Dumoulin, A., Janßen, A., Picavet, S., Vanthuyne, S., Eynde, R. V., Vanholder, R. C., Delanghe, J., Schoenmakere, G. D., Waele, J. J. D., et al. (2015) · Intensive Care Medicine · doi:10.1007/s00134-014-3641-9 · Cited by 135 · see citing works
Effect of a High-Protein Diet on Kidney Function in Healthy Adults: Results From the OmniHeart Trial
Juraschek, S. P., Appel, L. J., Anderson, C. A. M., & Miller, E. R. (2012) · American Journal of Kidney Diseases · doi:10.1053/j.ajkd.2012.10.017 · Cited by 108 · see citing works
Delanaye, P., Cavalier, E., Morel, J., Mehdi, M., Maillard, N., Claisse, G., Lambermont, B. C., Dubois, B., Damas, P., Krzesinski, J.-M., et al. (2014) · BMC Nephrology · doi:10.1186/1471-2369-15-9 · Cited by 90 · see citing works
The renal hemodynamic response to amino acid infusion in the rat.
Meyer, T. W., Ichikawa, I., Zatz, R., & Brenner, B. M. (1983) · PubMed · Cited by 75 · see citing works
Singer, P. (2007) · Wiener klinische Wochenschrift · doi:10.1007/s00508-007-0794-3 · Cited by 73 · see citing works
Hypocaloric, High‐Protein Nutrition Therapy in Older vs Younger Critically Ill Patients With Obesity
Dickerson, R. N., Medling, T. L., Smith, A. C., Maish, G. O., Croce, M. A., Minard, G., & Brown, R. O. (2012) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607112466894 · Cited by 65 · see citing works
Roberts, P. R., BLACK, K. W., & Zaloga, G. P. (1997) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.156.4.9607003 · Cited by 55 · see citing works
Bagshaw, S. M., Uchino, S., Kellum, J. A., Morimatsu, H., Morgera, S., Schetz, M., Tan, I. K. S., Bouman, C. S. C., Macedo, E. M., Gibney, R. T. N., et al. (2013) · Journal of Critical Care · doi:10.1016/j.jcrc.2013.08.002 · Cited by 48 · see citing works
Self-citationRenal plasma flow and glomerular filtration rate duringacute kidney injury in man
Prowle, J. R., Ishikawa, K., May, C. N., & Bellomo, R. (2010) · Renal Failure · doi:10.3109/08860221003611695 · Cited by 28 · see citing works
Self-citationSimpson, F. O., Sweetman, E. A., & Doig, G. S. (2010) · Trials · doi:10.1186/1745-6215-11-17 · Cited by 24 · see citing works
Self-citationRegulation of renal hemodynamics after protein feeding: effects of proximal and distal diuretics
Woods, L. L., Smith, B. E., & Young, D. R. D. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.264.2.r337 · Cited by 16 · see citing works
Doig, G., Simpson, F., Sweetmant, E., & Bellomo, R. (2009) · doi:10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a1567 · Cited by 7 · see citing works
Self-citationDoig, G. S. (2008) · JAMA · doi:10.1001/jama.2008.826 · Cited by 1 · see citing works
Self-citation
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ESPEN guideline on clinical nutrition in the intensive care unit.
Singer, P., Blaser, A. R., Berger, M. M., Alhazzani, W., Calder, P. C., Casaer, M. P., Hiesmayr, M., Mayer, K., Montejo, J. C., Pichard, C., et al. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.08.037 · Cited by 2,904 · see citing works
Compher, C., Bingham, A. L., McCall, M., Patel, J., Rice, T. W., Braunschweig, C., & McKeever, L. (2022) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2267 · Cited by 747 · see citing works
Renal recovery after acute kidney injury
Forni, L. G., Darmon, M., Ostermann, M., Straaten, H. M. O., Pettilä, V., Prowle, J. R., Schetz, M., & Joannidis, M. (2017) · Intensive Care Medicine · doi:10.1007/s00134-017-4809-x · Cited by 442 · see citing works
van Zanten, A. R. H., Waele, E. D., & Wischmeyer, P. E. (2019) · Critical Care · doi:10.1186/s13054-019-2657-5 · Cited by 348 · see citing works
Joannidis, M., Druml, W., Forni, L. G., Groeneveld, A. B. J., Honoré, P. M., Hoste, E. A. J., Ostermann, M., Straaten, H. M. O., & Schetz, M. (2017) · Intensive Care Medicine · doi:10.1007/s00134-017-4832-y · Cited by 345 · see citing works
Egi, M., Ogura, H., Yatabe, T., Atagi, K., Inoue, S., Iba, T., Kakihana, Y., Kawasaki, T., Kushimoto, S., Kuroda, Y., et al. (2021) · Journal of Intensive Care · doi:10.1186/s40560-021-00555-7 · Cited by 226 · see citing works
The intensive care medicine research agenda in nutrition and metabolism
Arabi, Y. M., Casaer, M. P., Chapman, M. J., Heyland, D. K., Ichaï, C., Marik, P. E., Martindale, R. G., McClave, S. A., Preiser, J., Reignier, J., et al. (2017) · Intensive Care Medicine · doi:10.1007/s00134-017-4711-6 · Cited by 203 · see citing works
A Randomized Trial of Intravenous Amino Acids for Kidney Protection
Landoni, G., Monaco, F., Ti, L. K., Redaelli, M. B., Bradić, N., Comis, M., Kotani, Y., Brambillasca, C., Garofalo, E., Scandroglio, A. M., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2403769 · Cited by 193 · see citing works
Self-citationMonitoring nutrition in the ICU
Berger, M. M., Reintam-Blaser, A., Calder, P. C., Casaer, M., Hiesmayr, M. J., Mayer, K., Montejo, J. C., Pichard, C., Preiser, J.-C., van Zanten, A. R. H., et al. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2018.07.009 · Cited by 171 · see citing works
A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice
Preiser, J.-C., Arabi, Y. M., Berger, M. M., Casaer, M., McClave, S., Montejo-González, J. C., Peake, S., Reintam Blaser, A., Van den Berghe, G., van Zanten, A., et al. (2021) · Critical Care · doi:10.1186/s13054-021-03847-4 · Cited by 166 · see citing works
Intensive care unit–acquired weakness: unanswered questions and targets for future research
Piva, S., Fagoni, N., & Latronico, N. (2019) · F1000Research · doi:10.12688/f1000research.17376.1 · Cited by 150 · see citing works
Elke, G., Hartl, W. H., Kreymann, K. G., Adolph, M., Felbinger, T. W., Graf, T., de Heer, G., Heller, A. R., Kampa, U., Mayer, K., et al. (2019) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2019.05.002 · Cited by 150 · see citing works
Nutrition therapy in critical illness: a review of the literature for clinicians
Lambell, K., Tatucu-Babet, O. A., Chapple, L. S., Gantner, D. C., & Ridley, E. J. (2020) · Critical Care · doi:10.1186/s13054-020-2739-4 · Cited by 142 · see citing works
Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness
McNelly, A. S., Bear, D. E., Connolly, B. A., Arbane, G., Allum, L., Tarbhai, A., Cooper, J. A., Hopkins, P. A., Wise, M. P., Brealey, D. A., et al. (2020) · CHEST Journal · doi:10.1016/j.chest.2020.03.045 · Cited by 141 · see citing works
Renal functional reserve: from physiological phenomenon to clinical biomarker and beyond
Jufar, A. H., Lankadeva, Y. R., May, C. N., Cochrane, A. D., Bellomo, R., & Evans, R. G. (2020) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00237.2020 · Cited by 140 · see citing works
Self-citationLee, Z., Yap, C. S. L., Hasan, M. S., Engkasan, J. P., Yusof, B. N. M., Day, A. G., Patel, J. J., & Heyland, D. K. (2021) · Critical Care · doi:10.1186/s13054-021-03693-4 · Cited by 137 · see citing works
Understanding renal functional reserve
Ronco, C., Bellomo, R., & Kellum, J. A. (2017) · Intensive Care Medicine · doi:10.1007/s00134-017-4691-6 · Cited by 127 · see citing works
Self-citationNakamura, K., Nakano, H., Naraba, H., Mochizuki, M., Takahashi, Y., Sonoo, T., Hashimoto, H., & Morimura, N. (2020) · Clinical Nutrition · doi:10.1016/j.clnu.2020.07.036 · Cited by 114 · see citing works
Nutrition in the Intensive Care Unit—A Narrative Review
Hill, A., Elke, G., & Weimann, A. (2021) · Nutrients · doi:10.3390/nu13082851 · Cited by 114 · see citing works
on behalf of the Enhanced Recovery After Critical Illness Programme Group (ERACIP) investigators, Bear, D. E., Wandrag, L., Merriweather, J. L., Connolly, B. A., Hart, N., & Grocott, M. P. W. (2017) · Critical Care · doi:10.1186/s13054-017-1810-2 · Cited by 105 · see citing works
Husain‐Syed, F., Ferrari, F., Sharma, A., Danesi, T. H., Bezerra, P., López-Giacoman, S. R., Samoni, S., de Cal, M., Corradi, V., Virzì, G. M., et al. (2018) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfy227 · Cited by 103 · see citing works
Self-citationvan Zanten, A. R. H., Petit, L., Waele, J. J. D., Kieft, H., de Wilde, J., van Horssen, P., Klebach, M., & Hofman, Z. (2018) · Critical Care · doi:10.1186/s13054-018-2070-5 · Cited by 92 · see citing works
Post‐intensive care syndrome: Recent advances and future directions
Inoue, S., Nakanishi, N., Amaya, F., Fujinami, Y., Hatakeyama, J., Hifumi, T., Iida, Y., Kawakami, D., Kawai, Y., Kondo, Y., et al. (2024) · Acute Medicine & Surgery · doi:10.1002/ams2.929 · Cited by 98 · see citing works
Egi, M., Ogura, H., Yatabe, T., Atagi, K., Inoue, S., Iba, T., Kakihana, Y., Kawasaki, T., Kushimoto, S., Kuroda, Y., et al. (2021) · Acute Medicine & Surgery · doi:10.1002/ams2.659 · Cited by 86 · see citing works
Nutrition in the intensive care unit: from the acute phase to beyond
de Man, A., Gunst, J., & Blaser, A. R. (2024) · Intensive Care Medicine · doi:10.1007/s00134-024-07458-9 · Cited by 94 · see citing works
Preserving the quality of life: nutrition in the ICU
Singer, P. (2019) · Critical Care · doi:10.1186/s13054-019-2415-8 · Cited by 84 · see citing works
Metabolic support in the critically ill: a consensus of 19
Wernerman, J., Christopher, K. B., Annane, D., Casaer, M. P., Coopersmith, C. M., Deane, A. M., Waele, E. D., Elke, G., Ichaï, C., Karvellas, C. J., et al. (2019) · Critical Care · doi:10.1186/s13054-019-2597-0 · Cited by 84 · see citing works
Lee, Z., Dresen, E., Lew, C. C. H., Bels, J. L. M., Hill, A., Hasan, M. S., Ke, L., van Zanten, A. R. H., van de Poll, M. C. G., Heyland, D. K., et al. (2024) · Critical Care · doi:10.1186/s13054-023-04783-1 · Cited by 85 · see citing works
Singer, P., De Waele, E., Sanchez, C., Ruiz Santana, S., Montejo, J. C., Laterre, P. F., Soroksky, A., Moscovici, E., & Kagan, I. (2021) · Clinical Nutrition · doi:10.1016/j.clnu.2020.05.024 · Cited by 80 · see citing works
Nutrition in critical illness: a current conundrum
Hoffer, L., & Bistrian, B. (2016) · F1000Research · doi:10.12688/f1000research.9278.1 · Cited by 68 · see citing works
Toward nutrition improving outcome of critically ill patients: How to interpret recent feeding RCTs?
Gunst, J., Casaer, M. P., Preiser, J., Reignier, J., & den Berghe, G. V. (2023) · Critical Care · doi:10.1186/s13054-023-04317-9 · Cited by 77 · see citing works
DGEM-Leitlinie: „Klinische Ernährung in der Intensivmedizin“
Elke, G., Hartl, W. H., Kreymann, K. G., Adolph, M., Felbinger, T. W., Graf, T., de Heer, G., Heller, A. R., Kampa, U., Mayer, K., et al. (2018) · Aktuelle Ernährungsmedizin · doi:10.1055/a-0713-8179 · Cited by 76 · see citing works
Early Administration of Protein in Critically Ill Patients: A Retrospective Cohort Study
Bendavid, I., Zusman, O., Kagan, I., Theilla, M., Cohen, J., & Singer, P. (2019) · Nutrients · doi:10.3390/nu11010106 · Cited by 73 · see citing works
Dresen, E., Weißbrich, C., Fimmers, R., Putensen, C., & Stehle, P. (2021) · Clinical Nutrition · doi:10.1016/j.clnu.2021.02.021 · Cited by 72 · see citing works
Heyland, D. K., Day, A. G., Clarke, G., Hough, C. L., Files, D. C., Mourtzakis, M., Deutz, N. E. P., Needham, D. M., & Stapleton, R. (2019) · BMJ Open · doi:10.1136/bmjopen-2018-027893 · Cited by 71 · see citing works
Autophagy and Its Implications Against Early Full Nutrition Support in Critical Illness
Van Dyck, L., Casaer, M. P., & Gunst, J. (2018) · Nutrition in Clinical Practice · doi:10.1002/ncp.10084 · Cited by 70 · see citing works
Unoki, T., Hayashida, K., Kawai, Y., Taito, S., Ando, M., Iida, Y., Kasai, F., Kawasaki, T., Kozu, R., Kondo, Y., et al. (2023) · Journal of Intensive Care · doi:10.1186/s40560-023-00697-w · Cited by 73 · see citing works
Calorie delivery and clinical outcomes in the critically ill: a systematic review and meta-analysis
Parikh, H. G., Miller, A., Chapman, M., Moran, J. L., & Peake, S. L. (2016) · Critical Care and Resuscitation · doi:10.1016/s1441-2772(23)00927-4 · Cited by 69 · see citing works
Protein Delivery in the Intensive Care Unit: Optimal or Suboptimal?
Heyland, D. K., Weijs, P. J. M., Coss‐Bu, J. A., Taylor, B. E., Kristof, A. S., O’Keefe, G. E., & Martindale, R. G. (2017) · Nutrition in Clinical Practice · doi:10.1177/0884533617691245 · Cited by 65 · see citing works
Heyland, D. K., Patel, J. J., Bear, D. E., Sacks, G. S., Nixdorf, H., Dolan, J., Aloupis, M., Licastro, K., Jovanović, V., Rice, T. W., et al. (2018) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.1449 · Cited by 63 · see citing works
Protein-energy nutrition in the ICU is the power couple: A hypothesis forming analysis
Oshima, T., Deutz, N. E. P., Doig, G. S., Wischmeyer, P. E., & Pichard, C. (2015) · Clinical Nutrition · doi:10.1016/j.clnu.2015.10.016 · Cited by 58 · see citing works
Self-citationChapple, L. S., Summers, M. J., Bellomo, R., Chapman, M. J., Davies, A. R., Ferrie, S., Finnis, M., Hurford, S., Lange, K. M., Little, L., et al. (2020) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2059 · Cited by 58 · see citing works
Self-citationLooijaard, W. G. P. M., Dekker, I. M., Beishuizen, A., Girbes, A. R. J., Straaten, H. M. O., & Weijs, P. J. M. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2019.09.007 · Cited by 57 · see citing works
Ran, Z., Allingstrup, M. J., Perner, A., & Doig, G. S. (2018) · Critical Care Medicine · doi:10.1097/ccm.0000000000003221 · Cited by 54 · see citing works
Self-citationLi, C., Xu, L., Chen, G., Zhao, L., Luo, C., Zhou, B., Zhang, X., Wang, J., Zhao, J., Huang, J., et al. (2019) · British Journal Of Nutrition · doi:10.1017/s000711451900271x · Cited by 54 · see citing works
Nutrition support for critically ill patients
Al‐Dorzi, H. M., & Arabi, Y. M. (2021) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.2228 · Cited by 52 · see citing works
Protein delivery and clinical outcomes in the critically ill: a systematic review and meta-analysis
Davies, M. L., Chapple, L. S., Chapman, M. J., Moran, J. L., & Peake, S. (2017) · Critical Care and Resuscitation · doi:10.1016/s1441-2772(23)00783-4 · Cited by 52 · see citing works
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Chapple, L. S., Parry, S. M., & Schaller, S. J. (2022) · Current Osteoporosis Reports · doi:10.1007/s11914-022-00746-7 · Cited by 48 · see citing works
Nutritional Support in the ICU
Reignier, J., Rice, T. W., Arabi, Y. M., & Casaer, M. P. (2025) · BMJ · doi:10.1136/bmj-2023-077979 · Cited by 54 · see citing works
High protein intake during the early phase of critical illness: Yes or no?
Preiser, J.-C. (2018) · Critical Care · doi:10.1186/s13054-018-2196-5 · Cited by 44 · see citing works
Amino acid supplements in critically ill patients
Gunst, J., Vanhorebeek, I., Thiessen, S., & den Berghe, G. V. (2017) · Pharmacological Research · doi:10.1016/j.phrs.2017.12.007 · Cited by 42 · see citing works
de Azevedo, J. R. A., Lima, H. C. M., Montenegro, W. S., Souza, S. C. D. C., Nogueira, I. R. O. M., Silva, M. M., & Muniz, N. D. A. (2019) · Revista Brasileira de Terapia Intensiva · doi:10.5935/0103-507x.20190025 · Cited by 42 · see citing works
The clinical relevance and mechanism of skeletal muscle wasting
Duan, K., Gao, X., & Zhu, D. (2020) · Clinical Nutrition · doi:10.1016/j.clnu.2020.07.029 · Cited by 42 · see citing works
Patel, J. J., Martindale, R. G., & McClave, S. A. (2017) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607117721908 · Cited by 41 · see citing works
Should We Prescribe More Protein to Critically Ill Patients?
Heyland, D. K., Stapleton, R., & Compher, C. W. (2018) · Nutrients · doi:10.3390/nu10040462 · Cited by 40 · see citing works
Nutrition in the ICU: new trends versus old-fashioned standard enteral feeding?
Koekkoek, K. W. A. C., & van Zanten, A. R. H. (2018) · Current Opinion in Anaesthesiology · doi:10.1097/aco.0000000000000571 · Cited by 38 · see citing works
Hsu, C.-C., Sun, C.-Y., Tsai, C., Chen, M.-Y., Wang, S., Hsu, J., Yeh, C., & Yeh, T. (2021) · Journal of Multidisciplinary Healthcare · doi:10.2147/jmdh.s306350 · Cited by 37 · see citing works
Renal and Cerebral Hypoxia and Inflammation During Cardiopulmonary Bypass
Jufar, A. H., Lankadeva, Y. R., May, C. N., Cochrane, A. D., Marino, B., Bellomo, R., & Evans, R. G. (2021) · Comprehensive physiology · doi:10.1002/cphy.c210019 · Cited by 37 · see citing works
Self-citationRehal, M. S., Liebau, F., Tjäder, I., Norberg, Å., Rooyackers, O., & Wernerman, J. (2017) · Critical Care · doi:10.1186/s13054-017-1892-x · Cited by 35 · see citing works
Intermittent or continuous feeding: any difference during the first week?
Dyck, L. V., & Casaer, M. P. (2019) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000000617 · Cited by 33 · see citing works
Gabbai, F. B. (2017) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000380 · Cited by 33 · see citing works
Amino Acid Infusion for Perioperative Functional Renal Protection: A Meta-analysis
Pruna, A., Losiggio, R., Landoni, G., Kotani, Y., Redaelli, M. B., Veneziano, M., Lee, T. C., Zangrillo, A., Gaudino, M. F. L., Bellomo, R., et al. (2024) · Journal of Cardiothoracic and Vascular Anesthesia · doi:10.1053/j.jvca.2024.08.033 · Cited by 32 · see citing works
Self-citationClinical Nutrition of Critically Ill Patients in the Context of the Latest ESPEN Guidelines
Gostyńska, A., Stawny, M., Dettlaff, K., & Jelińska, A. (2019) · Medicina · doi:10.3390/medicina55120770 · Cited by 33 · see citing works
The flux of energy in critical illness and the obesity paradox
Jaitovich, A., & Hall, J. B. (2025) · Physiological Reviews · doi:10.1152/physrev.00029.2024 · Cited by 33 · see citing works
Should We Increase Protein Delivery During Critical Illness?
van Zanten, A. R. H. (2016) · Journal of Parenteral and Enteral Nutrition · doi:10.1177/0148607115626905 · Cited by 31 · see citing works
Moor, B. D., Vanwalleghem, J., Swennen, Q., Stas, K., & Meijers, B. K. I. (2018) · Clinical Kidney Journal · doi:10.1093/ckj/sfy022 · Cited by 31 · see citing works
Enteral nutrition in hospitalized adults
Gramlich, L., & Guenter, P. (2025) · New England Journal of Medicine · doi:10.1056/nejmra2406954 · Cited by 30 · see citing works
van Ruijven, I. M., Abma, J., Brunsveld‐Reinders, A. H., Stapel, S. N., van Etten‐Jamaludin, F. S., Boirie, Y., Barazzoni, R., & Weijs, P. J. M. (2023) · Clinical Nutrition · doi:10.1016/j.clnu.2023.09.026 · Cited by 29 · see citing works
Amino acids to prevent cardiac surgery-associated acute kidney injury: a randomized controlled trial
Kazawa, M., Kabata, D., Yoshida, H., Minami, K., Maeda, T., Yoshitani, K., Matsuda, H., & Shintani, A. (2024) · JA Clinical Reports · doi:10.1186/s40981-024-00703-6 · Cited by 29 · see citing works
Redaelli, M. B., Monaco, F., Bradić, N., Scandroglio, A. M., Ti, L. K., Belletti, A., Viscido, C., Licheri, M., Guarracino, F., Pruna, A., et al. (2024) · Anesthesiology · doi:10.1097/aln.0000000000005336 · Cited by 28 · see citing works
Self-citationNutrition Considerations in the Pediatric Cardiac Intensive Care Unit Patient
Justice, L. B., Buckley, J. R., Floh, A. A., Horsley, M., Alten, J. A., Anand, V., & Schwartz, S. M. (2018) · World Journal for Pediatric and Congenital Heart Surgery · doi:10.1177/2150135118765881 · Cited by 28 · see citing works
Protein metabolism and requirements in the ICU
Singer, P. (2020) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2020.03.026 · Cited by 28 · see citing works
Blaauw, L., Schoonees, A., Robertson, N. U., & Visser, J. (2024) · Clinical Nutrition ESPEN · doi:10.1016/j.clnesp.2024.04.003 · Cited by 27 · see citing works
Qin, Y., Huang, J., Ping, X., Zheng, H., Zhang, K., Xu, X., & Yu, J. (2024) · PeerJ · doi:10.7717/peerj.17433 · Cited by 28 · see citing works
Renal perfusion pressure: role and implications in critical illness
Panwar, R., McNicholas, B., Teixeira, J. P., & Kansal, A. (2025) · Annals of Intensive Care · doi:10.1186/s13613-025-01535-y · Cited by 32 · see citing works
Jufar, A. H., Evans, R. G., May, C. N., Hood, S. G., Betrie, A. H., Trask-Marino, A. L., Bellomo, R., & Lankadeva, Y. R. (2023) · Acta Physiologica · doi:10.1111/apha.13919 · Cited by 27 · see citing works
Self-citationParenteral nutrition in the ICU: Lessons learned over the past few years
Berger, M. M., & Pichard, C. (2018) · Nutrition · doi:10.1016/j.nut.2018.08.012 · Cited by 27 · see citing works
A critical view on primary and secondary outcome measures in nutrition trials
Arabi, Y. M., & Preiser, J.-C. (2017) · Intensive Care Medicine · doi:10.1007/s00134-017-4894-x · Cited by 26 · see citing works
Lew, C. C. H., Wong, G. J. Y., Cheung, K. P., Fraser, R. J., Chua, A. P., Chong, S. C., & Miller, M. (2019) · Critical Care · doi:10.1186/s13054-019-2500-z · Cited by 25 · see citing works
Optimizing Nitrogen Balance Is Associated with Better Outcomes in Neurocritically Ill Patients
Kim, T. J., Park, S.-H., Jeong, H.-B., Ha, E., Cho, W., Kang, H.-S., Kim, J. E., & Ko, S. (2020) · Nutrients · doi:10.3390/nu12103137 · Cited by 23 · see citing works
Lugli, A. K., de Watteville, A., Hollinger, A., Goetz, N., & Heidegger, C. P. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8091395 · Cited by 26 · see citing works
Heuts, S., Lee, Z., Lew, C. C. H., Bels, J. L. M., Gabrio, A., Kawczynski, M. J., Heyland, D. K., Summers, M. J., Deane, A. M., Mesotten, D., et al. (2024) · Critical Care Medicine · doi:10.1097/ccm.0000000000006562 · Cited by 27 · see citing works
Lew, C. C. H., Lee, Z., Day, A. G., Jiang, X., Bear, D. E., Jensen, G. L., Ng, P. Y., Tweel, L. E., Parillo, A., Heyland, D. K., et al. (2024) · CHEST Journal · doi:10.1016/j.chest.2024.02.008 · Cited by 26 · see citing works
Protein Requirements in Critically Ill Older Adults
Deer, R., & Volpi, E. (2018) · Nutrients · doi:10.3390/nu10030378 · Cited by 25 · see citing works
Martínez‐García, M. Á., González, J. C. M., y Mateos, A. G.-D.-L., & Teijeira, S. (2019) · Clinical Nutrition · doi:10.1016/j.clnu.2019.05.027 · Cited by 26 · see citing works
Intravenous amino acid for kidney protection: current understanding and future perspectives
Kotani, Y., Redaelli, M. B., Pruna, A., Losiggio, R., Cocozza, S., Ti, L. K., Bradić, N., Comis, M., Landoni, G., & Bellomo, R. (2024) · Clinical Kidney Journal · doi:10.1093/ckj/sfae409 · Cited by 23 · see citing works
Self-citationLooijaard, W. G. P. M., Denneman, N., Broens, B., Girbes, A. R. J., Weijs, P. J. M., & Straaten, H. M. O. (2018) · Clinical Nutrition · doi:10.1016/j.clnu.2018.11.012 · Cited by 22 · see citing works
Hill, A., Heyland, D. K., Elke, G., Schaller, S. J., Stocker, R. A., Haberthür, C., von Loeffelholz, C., Suchner, U., Puthucheary, Z., Bear, D. E., et al. (2020) · Nutrition Research Reviews · doi:10.1017/s0954422420000165 · Cited by 23 · see citing works
Guan, X., Chen, D., & Xu, Y. (2024) · Journal of Intensive Medicine · doi:10.1016/j.jointm.2023.12.002 · Cited by 23 · see citing works
Nutrition and autophagy deficiency in critical illness
Vanhorebeek, I., Casaer, M. P., & Gunst, J. (2023) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000001056 · Cited by 24 · see citing works
High protein intake without concerns?
Rooyackers, O., Rehal, M. S., Liebau, F., Norberg, Å., & Wernerman, J. (2017) · Critical Care · doi:10.1186/s13054-017-1699-9 · Cited by 22 · see citing works
Early Supplemental Parenteral Nutrition in Critically Ill Children: An Update
Jacobs, A., Verlinden, I., Vanhorebeek, I., & den Berghe, G. V. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8060830 · Cited by 23 · see citing works
Novel insights in endocrine and metabolic pathways in sepsis and gaps for future research
Téblick, A., Gunst, J., Langouche, L., & den Berghe, G. V. (2022) · Clinical Science · doi:10.1042/cs20211003 · Cited by 21 · see citing works
Nakanishi, N., Matsushima, S., Tatsuno, J., Liu, K., Tamura, T., Yonekura, H., Yamamoto, N., Unoki, T., Kondo, Y., & Nakamura, K. (2022) · Nutrients · doi:10.3390/nu14224849 · Cited by 21 · see citing works
High‐Protein Hypocaloric Nutrition for Non‐Obese Critically Ill Patients
Hoffer, L. J. (2018) · Nutrition in Clinical Practice · doi:10.1002/ncp.10091 · Cited by 18 · see citing works
Protein intake and outcome in critically ill patients
Arabi, Y. M., Al‐Dorzi, H. M., & Sadat, M. (2019) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0000000000000619 · Cited by 19 · see citing works
Outcome Measures in Critical Care Nutrition Interventional Trials: A Systematic Review
Chapple, L. S., Summers, M. J., Weinel, L. M., & Deane, A. M. (2020) · Nutrition in Clinical Practice · doi:10.1002/ncp.10478 · Cited by 19 · see citing works
Diretriz BRASPEN de Terapia Nutricional no Paciente Grave
Castro, M. G., Ribeiro, P. C., de Matos, L. B. N., de Abreu, H. B., de Assis, T., Barreto, P. A., Ceniccola, G. D., da Cunha, H. F. R., Gonçalves, R. C., Gonçalves, T. J. M., et al. (2023) · Braspen Journal · doi:10.37111/braspenj.diretrizdoentegrave · Cited by 18 · see citing works
Parenteral nutrition in the critically ill
Gunst, J., & den Berghe, G. V. (2017) · Current Opinion in Critical Care · doi:10.1097/mcc.0000000000000385 · Cited by 18 · see citing works
Chourdakis, M., Grammatikopoulou, M. G., Day, A. G., Bouras, E., & Heyland, D. K. (2018) · Clinical Nutrition · doi:10.1016/j.clnu.2018.12.006 · Cited by 18 · see citing works
- Authors
- Doig, G. S., Simpson, F., Bellomo, R., Heighes, P. T., Sweetman, E. A., Chesher, D., Pollock, C., Davies, A., Botha, J., Harrigan, P., & Reade, M. C.
- Affiliations
- The University of Sydney (AU)
- Monash University (AU)
- John Hunter Hospital (AU)
- The University of Queensland (AU)
- Corresponding author
- Doig, Gordon S.
- ORCID
- Venue
- Intensive Care Medicine
- Published
- 2015-04-30
- Volume
- 41
- Issue
- 7
- Pages
- 1197-1208
- ISSN
- 0342-4642 (ISSN-L)
- 1432-1238
- OpenAlex
- W2010536286
- Cited by
- 232
- References
- 40
- Citations by year
- 2026: 11 · 2025: 24 · 2024: 34 · 2023: 17 · 2022: 16 · 2021: 20 · 2020: 18 · 2019: 28 · 2018: 30 · 2017: 21 · 2016: 9 · 2015: 4
- FWCI
- 18.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Intensive Care Medicine (publishedVersion)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Health and Medical Research Council (632614)
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Nursing › Nutrition and Dietetics › Clinical Nutrition and Gastroenterology
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- intravenous amino acids, acute kidney injury, critically ill patients, renal function preservation, estimated glomerular filtration rate, cystatin C, renal replacement therapy, fluid balance, urine output, intensive care unit, APACHE II score, dietary supplementation, ICU length of stay
- MeSH terms
- Aged, Amino Acids, Creatinine, Female, Glomerular Filtration Rate, Humans, Intensive Care Units, Male, Middle Aged, Critical Illness, Cystatin C, Acute Kidney Injury
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