Effect of Protein Dosage on Persistent Acute Renal Failure in Critically Ill Patients.

NCT07631221 | Recruiting

• 1 other identifier: 7355
• Study Type: observational
• Target: 344
• Locations: 1 country
• Sites: 6

Brief Summary

Background: Acute kidney injury (AKI) is common in critically ill patients and is associated with worse outcomes, including longer ICU stay, need for dialysis, and higher mortality. Patients with AKI often experience significant protein and calorie loss due to their illness and medical treatments. Providing the right amount of protein may help maintain muscle mass and improve recovery; however, consuming too much protein could potentially worsen kidney function. Current international guidelines recommend adequate protein intake, but the best dose remains uncertain, especially for patients with AKI. Study Purpose: This research will examine whether patients with AKI who receive a higher protein intake (greater than 1.2 g/kg/day) have different outcomes compared to those who receive a standard or lower protein intake (≤1.2 g/kg/day). The primary outcome is whether a higher protein intake leads to a longer recovery time from AKI or worsens kidney function. Study Design: This is a retrospective, multicenter study using data from five hospitals in Argentina. It is designed as a "target trial emulation," meaning researchers will analyze existing patient data as if it were a randomized clinical trial. Patients will be included on the fifth day of their ICU stay and classified into two groups based on their protein intake on day 5:

• Group 1 (Standard Protein): ≤1.2 g/kg/day
• Group 2 (High Protein): \>1.2 g/kg/day No additional interventions will be performed; data are collected from medical records. Study Population: The study will include adult patients (≥18 years) admitted to the ICU who are receiving exclusive enteral or parenteral nutrition and have AKI (or worsening chronic kidney disease) according to KDIGO criteria. Patients with advanced chronic kidney disease (creatinine clearance \<30 ml/min/1.73 m²) or undergoing hemodialysis at T0, previous kidney transplant, severe liver disease, or BMI \>30 will be excluded. Outcomes:
• Primary Outcome: Time to recovery of kidney function within 30 days, measured by creatinine returning close to baseline values.
• Secondary Outcomes: Changes in blood urea levels, duration of renal replacement therapy (hemodialysis), ICU length of stay, and 30-day mortality. Statistical Approach: To minimize bias, the study will use advanced statistical methods, including propensity score weighting, to ensure fair comparison between groups. Competing risks (such as death before kidney recovery) will be taken into account in the analysis. Significance: This study will provide important information about the safety and effectiveness of higher protein intake in critically ill patients with AKI. The findings may help guide nutritional strategies in the ICU, optimize kidney outcomes, and improve patient care.

Conditions

Acute Kidney Failure; Critical Illness; Nutritional Support; Mortality in Intensive Care Units; Protein Intake

Keywords

Acute Kidney Injury; Critical Illness; Protein Intake; Target Trial Emulation; Intensive Care Unit; Nutritional Support

Outcome Measures

Primary Outcomes (1)

• Time to recovery of kidney function

  Recovery of kidney function will be defined as the serum creatinine returning to ≤1.5 times the baseline value or ≤30% above the baseline value, with death considered a competing event. The analysis will compare patients receiving ≤1.2 g/kg/day vs. \>1.2 g/kg/day of protein intake on ICU day 5.

  Within 30 days from ICU day 5 (Time Zero) or until ICU discharge, whichever occurs first.

Secondary Outcomes (3)

• Change in blood urea levels at day 14

  14 days from ICU stay (T0)

• ICU length of stay

  Within 30 days from ICU day 5 (Time Zero) or until ICU discharge, whichever occurs first.

• Mortality at 30 days

  Within 30 days or until hospital discharge, whichever occurs first.

Study Arms (2)

Patients whose protein intake at T0 is 1.2 g/kg/day or less.

Patients in this group will be those whose documented protein intake on ICU day 5 is ≤1.2 g/kg/day. No additional interventions are administered as part of the study; classification is based solely on protein intake recorded in the medical record.

Patients whose protein intake at T0 is greater than or equal to 1.2 g/kg/day.

Patients in this group will be those whose documented protein intake on ICU day 5 is greater than 1.2 g/kg/day. No additional interventions are administered as part of the study; classification is based solely on protein intake recorded in the medical record.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population consists of critically ill adult patients (≥18 years) admitted to intensive care units at five tertiary hospitals in Argentina. Eligible patients are those receiving exclusive enteral or parenteral nutrition who present with acute kidney injury (AKI) or worsening chronic kidney disease according to KDIGO criteria. Patients with advanced chronic kidney disease (creatinine clearance \<30 ml/min/1.73 m²) or hemodialysis at admission, previous kidney transplant, severe liver disease, or body mass index (BMI) \>30 are excluded.

You may qualify if:

• Patients aged 18 years or older admitted to the ICU.
• Patients receiving exclusive enteral or parenteral nutrition
• Acute kidney injury or exacerbated chronic kidney disease according to KDIGO criteria (increase in creatinine greater than 0.3 mg/dL in less than 48 hours or a 1.5-fold increase in baseline creatinine in 7 days)

You may not qualify if:

• Patients diagnosed with chronic kidney disease with a creatinine clearance of less than 30 ml/min/m2 or on dialysis at admission.
• Patients with a history of kidney transplantation
• Patients with severe liver disease (Child-Pugh score \>7 points)
• Patients with acute kidney injury undergoing renal replacement therapy at T0
• BMI\> 30

Sponsors & Collaborators

• Hospital Italiano de Buenos Aires: lead

Study Sites (6)

Clinica Bazterrica

Buenos Aires, Buenos Aires, Argentina

NOT YET RECRUITING

Hospital Alemán

Buenos Aires, Buenos Aires F.D., C1118AAT, Argentina

NOT YET RECRUITING

Hospital Italiano de Buenos Aires

Buenos Aires, Buenos Aires F.D., C1199ABB, Argentina

RECRUITING

Hospital Privado Universitario de Córdoba

Córdoba, Córdoba Province, X5016KEH, Argentina

RECRUITING

Hospital Universitario Austral

Buenos Aires, Pilar, B1629AHJ, Argentina

RECRUITING

Hospital Italiano sede San Justo Agustín Rocca

Buenos Aires, San Justo, C1198AAW, Argentina

RECRUITING

Related Publications (12)

• Yehya N, Harhay MO, Curley MAQ, Schoenfeld DA, Reeder RW. Reappraisal of Ventilator-Free Days in Critical Care Research. Am J Respir Crit Care Med. 2019 Oct 1;200(7):828-836. doi: 10.1164/rccm.201810-2050CP.

  PMID: 31034248 BACKGROUND

• Doig GS, Simpson F, Bellomo R, Heighes PT, Sweetman EA, Chesher D, Pollock C, Davies A, Botha J, Harrigan P, Reade MC. Intravenous amino acid therapy for kidney function in critically ill patients: a randomized controlled trial. Intensive Care Med. 2015 Jul;41(7):1197-208. doi: 10.1007/s00134-015-3827-9. Epub 2015 Apr 30.

  PMID: 25925203 BACKGROUND

• Rosa-Diez GJ, Varela F, Crucelegui S, Algranati SL, Greloni G. [Comparison between CKD-EPI and MDRD-equations to estimate glomerular filtration rate in chronic kidney disease patients]. Medicina (B Aires). 2011;71(4):323-30. Spanish.

  PMID: 21893444 BACKGROUND

• Deane AM, Casaer MP. Editorial: The interaction between protein delivery and blood urea and ammonia during critical illness. Curr Opin Clin Nutr Metab Care. 2024 Mar 1;27(2):144-146. doi: 10.1097/MCO.0000000000001016. Epub 2024 Feb 8. No abstract available.

  PMID: 38320160 BACKGROUND

• Haines RW, Zolfaghari P, Wan Y, Pearse RM, Puthucheary Z, Prowle JR. Elevated urea-to-creatinine ratio provides a biochemical signature of muscle catabolism and persistent critical illness after major trauma. Intensive Care Med. 2019 Dec;45(12):1718-1731. doi: 10.1007/s00134-019-05760-5. Epub 2019 Sep 17.

  PMID: 31531715 BACKGROUND

• Gunst J, Kashani KB, Hermans G. The urea-creatinine ratio as a novel biomarker of critical illness-associated catabolism. Intensive Care Med. 2019 Dec;45(12):1813-1815. doi: 10.1007/s00134-019-05810-y. Epub 2019 Oct 16. No abstract available.

  PMID: 31620835 BACKGROUND

• Haines RW, Prowle JR, Day A, Bear DE, Heyland DK, Puthucheary Z. Association between urea trajectory and protein dose in critically ill adults: a secondary exploratory analysis of the effort protein trial (RE-EFFORT). Crit Care. 2024 Jan 16;28(1):24. doi: 10.1186/s13054-024-04799-1.

  PMID: 38229072 BACKGROUND

• Heyland DK, Patel J, Compher C, Rice TW, Bear DE, Lee ZY, Gonzalez VC, O'Reilly K, Regala R, Wedemire C, Ibarra-Estrada M, Stoppe C, Ortiz-Reyes L, Jiang X, Day AG; EFFORT Protein Trial team. The effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicentre, pragmatic, registry-based randomised trial. Lancet. 2023 Feb 18;401(10376):568-576. doi: 10.1016/S0140-6736(22)02469-2. Epub 2023 Jan 25.

  PMID: 36708732 BACKGROUND

• Kellum JA, Sileanu FE, Bihorac A, Hoste EA, Chawla LS. Recovery after Acute Kidney Injury. Am J Respir Crit Care Med. 2017 Mar 15;195(6):784-791. doi: 10.1164/rccm.201604-0799OC.

  PMID: 27635668 BACKGROUND

• Hoste E, Bihorac A, Al-Khafaji A, Ortega LM, Ostermann M, Haase M, Zacharowski K, Wunderink R, Heung M, Lissauer M, Self WH, Koyner JL, Honore PM, Prowle JR, Joannidis M, Forni LG, Kampf JP, McPherson P, Kellum JA, Chawla LS; RUBY Investigators. Identification and validation of biomarkers of persistent acute kidney injury: the RUBY study. Intensive Care Med. 2020 May;46(5):943-953. doi: 10.1007/s00134-019-05919-0. Epub 2020 Feb 6.

  PMID: 32025755 BACKGROUND

• Patel JJ, McClain CJ, Sarav M, Hamilton-Reeves J, Hurt RT. Protein Requirements for Critically Ill Patients With Renal and Liver Failure. Nutr Clin Pract. 2017 Apr;32(1_suppl):101S-111S. doi: 10.1177/0884533616687501. Epub 2017 Feb 16.

  PMID: 28208022 BACKGROUND

• Sabatino A, Fiaccadori E, Barazzoni R, Carrero JJ, Cupisti A, De Waele E, Jonckheer J, Cuerda C, Bischoff SC. ESPEN practical guideline on clinical nutrition in hospitalized patients with acute or chronic kidney disease. Clin Nutr. 2024 Sep;43(9):2238-2254. doi: 10.1016/j.clnu.2024.08.002. Epub 2024 Aug 20.

  PMID: 39178492 BACKGROUND

MeSH Terms

Conditions

Acute Kidney Injury; Critical Illness

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ivan Alfredo Huespe, MS

  Hospital Italiano de Buenos Aires

  STUDY DIRECTOR

Central Study Contacts

Ivan Alfredo Huespe, MS

CONTACT

+54949590200; ivan.huespe@hospitalitaliano.org.ar

Veronica Ester Monzon, MS

CONTACT

+54949590200; veronica.monzon@hospitalitaliano.org.ar

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Section of Critical Care Research and Innovation, Hospital Italiano de Buenos Aires

Study Record Dates

• First Submitted: June 1, 2026
• First Posted: June 5, 2026
• Study Start: September 15, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 5, 2026

Record last verified: 2026-06

Locations

AR (6)