Acute Kidney FailureNCT07631221
Effect of Protein Dosage on Persistent Acute Renal Failure in Critically Ill Patients.
An observational study of Acute Kidney Failure and Critical Illness, run by Hospital Italiano de Buenos Aires at 6 sites in Argentina.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Failure, Critical Illness, Protein Intake
- How many people
- 344 participants
- Where
- 6 sitesArgentina
- Study dates
- 15 Sep 2025to 1 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
Argentina6 sites, 6 recruiting
- Not yet recruiting
Clinica Bazterrica
Buenos Aires, Buenos Aires
Nicolas David Falcon, MD, +5491148211600 ext. 51724, nicolas.david.falcon@gmail.com
- Not yet recruiting
Hospital Alemán
Buenos Aires, Buenos Aires F.D., C1118AAT
Daniel Ignacio Ivulich, MD, +5491161859413, di.ivulich@gmail.com
- Recruiting
Hospital Italiano de Buenos Aires
Buenos Aires, Buenos Aires F.D., C1199ABB
Ivan Alfredo Huespe, MD, MPh, +5493425382554, ivan.huespe@hospitalitaliano.org.ar
- Recruiting
Hospital Universitario Austral
Buenos Aires, Pilar, B1629AHJ
Alicia Gira, MD, +5491126336442, aliciaroxanagira@gmail.com
- Recruiting
Hospital Italiano sede San Justo Agustín Rocca
Buenos Aires, San Justo, C1198AAW
Veronica Ester Monzon, MD, +5491165846854, veronica.monzon@hospitalitaliano.org.ar
- Recruiting
Hospital Privado Universitario de Córdoba
Córdoba, Córdoba Province, X5016KEH
Emiliano Tornu, MD, +5491164073575, emilianocornu@gmail.com
About this study
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.
Read more
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.
Read the detailed description
Background:
Acute kidney injury (AKI) is a frequent complication in critically ill patients and is associated with prolonged hospital stay, need for renal replacement therapy (RRT), and higher mortality. Patients with AKI often develop protein-calorie malnutrition due to increased catabolism, inflammation, and nutrient losses. This is further aggravated when RRT is required, as dialysis contributes to nitrogen and amino acid losses. Clinical guidelines recommend providing an adequate protein intake to support recovery; however, the optimal protein dose remains uncertain.
Recent trials, such as the EFFORT Protein study, suggest that higher protein intake may benefit some critically ill patients, especially those with malnutrition or frailty. However, the same study also indicated potential harm in patients with severe illness or AKI, showing that excessive protein intake (>2.2 g/kg/day) could worsen kidney outcomes and increase mortality.
Given the uncertainty regarding the actual effect of increased protein intake in patients with AKI-and the possibility that it may be harmful in those with persistent AKI-this study uses a Target Trial Emulation approach to evaluate whether protein intake on the fifth day of ICU admission exceeding 1.2 g/kg/day leads to prolonged duration of AKI in critically ill patients.
Objective:
This study aims to evaluate whether a higher protein intake (>1.2 g/kg/day) compared with standard or lower intake (≤1.2 g/kg/day) affects the duration of AKI and clinical outcomes in critically ill patients.
Study Design:
This is a retrospective, multicenter study using a target trial emulation design. Patient data will be collected from electronic health records of five tertiary hospitals in Argentina. Eligible patients will be identified on the fifth day of their ICU admission, referred to as Time Zero (T0). Classification into treatment groups will depend on protein intake at T0:
- Group 1: Standard protein intake (≤1.2 g/kg/day)
- Group 2: High protein intake (>1.2 g/kg/day) No interventions will be administered as part of the study; data will be analyzed retrospectively.
Population:
Inclusion criteria: age ≥18 years, ICU admission, exclusive enteral or parenteral nutrition, and presence of AKI or worsening chronic kidney disease as defined by KDIGO criteria (rise in serum creatinine >0.3 mg/dL within 48 hours, or 1.5-fold increase within 7 days).
Exclusion criteria: advanced chronic kidney disease (creatinine clearance <30 ml/min/1.73 m²) or dialysis at admission, prior kidney transplant, severe liver disease (Child-Pugh >7), AKI requiring RRT at baseline (T0), or body mass index >30.
Primary Outcome: Time to recovery of kidney function within 30 days, defined as return of serum creatinine to ≤1.5 times baseline or ≤30% above baseline, with death considered as a competing event.
Secondary Outcomes:
- Change in blood urea levels at day 14.
- Daily change in urea trajectory during the first 14 days.
- Days free of AKI and days free of RRT within 30 days.
- Mortality at day 30.
- ICU length of stay within 30 days.
- Reasons for initiation of RRT.
Sample Size: Based on prior literature, we estimated that 172 patients per group are required for non-inferiority testing with 80% power, α = 0.05, and a non-inferiority margin of 2 days of AKI. Adjustments for potential confounders indicate that at least 105 patients per group will be necessary.
Statistical Analysis:
- Primary analysis will be conducted on an intention-to-treat basis.
- Propensity score weighting with inverse probability of treatment weighting (IPTW) will be used to adjust for baseline differences between groups.
- For time-to-event outcomes (e.g., AKI recovery, ICU discharge, mortality), competing risks will be addressed using Fine-Gray regression.
- Continuous outcomes (e.g., urea levels) will be compared using t-tests or Mann-Whitney tests, depending on distribution. Longitudinal changes in urea will be analyzed using mixed-effects models with restricted cubic splines.
- Proportions (e.g., mortality) will be compared using logistic regression models adjusted with propensity score weighting.
Ethical Considerations:
This study involves a retrospective review of de-identified patient data. It poses minimal risk, as no interventions are introduced beyond standard care. Confidentiality will be strictly maintained in accordance with national and local regulations, including Argentina's Personal Data Protection Law (Law 25,326). Informed consent will be waived in accordance with CIOMS guidelines, as the study is retrospective, presents minimal risk, and has significant social and scientific value.
Significance:
This study will provide new evidence on the safety and effectiveness of protein dosing in critically ill patients with AKI. The results may inform future guidelines on nutritional therapy in the ICU and optimize outcomes for patients at high risk of kidney complications.
- Conditions
- Acute Kidney Failure, Critical Illness, Protein Intake, Nutritional Support, Mortality in Intensive Care Units
- Keywords
- Acute Kidney Injury, Critical Illness, Protein Intake, Target Trial Emulation, Intensive Care Unit, Nutritional Support
- Medical subject headings
- Acute Kidney Injury, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Comparison of serum urea concentration between groups at day 14 after ICU day 5 (Time Zero). The outcome will assess whether patients with higher protein intake (>1.2 g/kg/day) show different urea values compared with those with standard intake (≤1.2 g/kg/day).
Measured: 14 days from ICU stay (T0)
ICU length of stay
Comparison of the duration of ICU stay between groups classified by protein intake on day 5 of ICU stay. Discharge will be considered the endpoint, with death treated as a competing event in the analysis.
Measured: Within 30 days from ICU day 5 (Time Zero) or until ICU discharge, whichever occurs first.
Mortality at 30 days
Proportion of patients who die within 30 days. The outcome will compare mortality rates between patients with higher protein intake (>1.2 g/kg/day) and those with standard intake (≤1.2 g/kg/day).
Measured: Within 30 days or until hospital discharge, whichever occurs first.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2026
- Study start15 Sep 2025
- Primary completion31 Aug 2026 (estimated)
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 344 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Italiano de Buenos Aires
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ivan A. Huespe, Hospital Italiano de Buenos Aires
- Investigators
- Ivan Alfredo Huespe, MS, Study director, Hospital Italiano de Buenos Aires
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07631221
- Sponsor's protocol ID
- 7355
- Status last verified
- Jun 2026
- First submitted
- 1 Jun 2026
- Last updated
- 5 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The study team is currently evaluating the feasibility of sharing de-identified individual participant data, taking into account ethical approvals, data privacy regulations, and the resources required for proper anonymization and curation. A final plan will be determined after completion of data collection and primary analyses.
Publications
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.
PubMed 31034248Doig 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.
PubMed 25925203Rosa-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.
PubMed 21893444Deane 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.
PubMed 38320160Haines 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.
PubMed 31531715Gunst 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.
PubMed 31620835Haines 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.
PubMed 38229072Heyland 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.
PubMed 36708732Kellum 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.
PubMed 27635668Hoste 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.
PubMed 32025755Patel 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.
PubMed 28208022Sabatino 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.
PubMed 39178492
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Protein Dosage on Persistent Acute Renal Failure in Critically Ill Patients.
- ClinicalTrials.gov ID
- NCT07631221
- Acronym / sponsor ID
- 7355
- Conditions
- Acute Kidney Failure, Critical Illness, Protein Intake, Nutritional Support, Mortality in Intensive Care Units
- Keywords
- Acute Kidney Injury, Critical Illness, Protein Intake, Target Trial Emulation, Intensive Care Unit, Nutritional Support
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 344 participants (estimated)
- Lead sponsor
- Hospital Italiano de Buenos AiresUniversity, hospital or other
- Study start
- 15 Sep 2025 (actual)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 5 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background:
Acute kidney injury (AKI) is a frequent complication in critically ill patients and is associated with prolonged hospital stay, need for renal replacement therapy (RRT), and higher mortality. Patients with AKI often develop protein-calorie malnutrition due to increased catabolism, inflammation, and nutrient losses. This is further aggravated when RRT is required, as dialysis contributes to nitrogen and amino acid losses. Clinical guidelines recommend providing an adequate protein intake to support recovery; however, the optimal protein dose remains uncertain.
Recent trials, such as the EFFORT Protein study, suggest that higher protein intake may benefit some critically ill patients, especially those with malnutrition or frailty. However, the same study also indicated potential harm in patients with severe illness or AKI, showing that excessive protein intake (>2.2 g/kg/day) could worsen kidney outcomes and increase mortality.
Given the uncertainty regarding the actual effect of increased protein intake in patients with AKI-and the possibility that it may be harmful in those with persistent AKI-this study uses a Target Trial Emulation approach to evaluate whether protein intake on the fifth day of ICU admission exceeding 1.2 g/kg/day leads to prolonged duration of AKI in critically ill patients.
Objective:
This study aims to evaluate whether a higher protein intake (>1.2 g/kg/day) compared with standard or lower intake (≤1.2 g/kg/day) affects the duration of AKI and clinical outcomes in critically ill patients.
Study Design:
This is a retrospective, multicenter study using a target trial emulation design. Patient data will be collected from electronic health records of five tertiary hospitals in Argentina. Eligible patients will be identified on the fifth day of their ICU admission, referred to as Time Zero (T0). Classification into treatment groups will depend on protein intake at T0:
- Group 1: Standard protein intake (≤1.2 g/kg/day)
- Group 2: High protein intake (>1.2 g/kg/day) No interventions will be administered as part of the study; data will be analyzed retrospectively.
Population:
Inclusion criteria: age ≥18 years, ICU admission, exclusive enteral or parenteral nutrition, and presence of AKI or worsening chronic kidney disease as defined by KDIGO criteria (rise in serum creatinine >0.3 mg/dL within 48 hours, or 1.5-fold increase within 7 days).
Exclusion criteria: advanced chronic kidney disease (creatinine clearance <30 ml/min/1.73 m²) or dialysis at admission, prior kidney transplant, severe liver disease (Child-Pugh >7), AKI requiring RRT at baseline (T0), or body mass index >30.
Primary Outcome: Time to recovery of kidney function within 30 days, defined as return of serum creatinine to ≤1.5 times baseline or ≤30% above baseline, with death considered as a competing event.
Secondary Outcomes:
- Change in blood urea levels at day 14.
- Daily change in urea trajectory during the first 14 days.
- Days free of AKI and days free of RRT within 30 days.
- Mortality at day 30.
- ICU length of stay within 30 days.
- Reasons for initiation of RRT.
Sample Size: Based on prior literature, we estimated that 172 patients per group are required for non-inferiority testing with 80% power, α = 0.05, and a non-inferiority margin of 2 days of AKI. Adjustments for potential confounders indicate that at least 105 patients per group will be necessary.
Statistical Analysis:
- Primary analysis will be conducted on an intention-to-treat basis.
- Propensity score weighting with inverse probability of treatment weighting (IPTW) will be used to adjust for baseline differences between groups.
- For time-to-event outcomes (e.g., AKI recovery, ICU discharge, mortality), competing risks will be addressed using Fine-Gray regression.
- Continuous outcomes (e.g., urea levels) will be compared using t-tests or Mann-Whitney tests, depending on distribution. Longitudinal changes in urea will be analyzed using mixed-effects models with restricted cubic splines.
- Proportions (e.g., mortality) will be compared using logistic regression models adjusted with propensity score weighting.
Ethical Considerations:
This study involves a retrospective review of de-identified patient data. It poses minimal risk, as no interventions are introduced beyond standard care. Confidentiality will be strictly maintained in accordance with national and local regulations, including Argentina's Personal Data Protection Law (Law 25,326). Informed consent will be waived in accordance with CIOMS guidelines, as the study is retrospective, presents minimal risk, and has significant social and scientific value.
Significance:
This study will provide new evidence on the safety and effectiveness of protein dosing in critically ill patients with AKI. The results may inform future guidelines on nutritional therapy in the ICU and optimize outcomes for patients at high risk of kidney complications.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Time to recovery of kidney function
Time frame: Within 30 days from ICU day 5 (Time Zero) or until ICU discharge, whichever occurs first.
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.
3 secondary outcomes
Change in blood urea levels at day 14
Time frame: 14 days from ICU stay (T0)
ICU length of stay
Time frame: Within 30 days from ICU day 5 (Time Zero) or until ICU discharge, whichever occurs first.
Mortality at 30 days
Time frame: Within 30 days or until hospital discharge, whichever occurs first.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2026.
- Background: PubMed 31034248Yehya 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.
- Background: PubMed 25925203Doig 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.
- Background: PubMed 21893444Rosa-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.
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- Individual participant dataSharing planned: Undecided. The study team is currently evaluating the feasibility of sharing de-identified individual participant data, taking into account ethical approvals, data privacy regulations, and the resources required for proper anonymization and curation. A final plan will be determined after completion of data collection and primary analyses.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ivan Alfredo Huespe, MS study director
Hospital Italiano de Buenos Aires
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Kidney Failure and Critical Illness, run by Hospital Italiano de Buenos Aires at 6 sites in Argentina.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ivan Alfredo Huespe, MS (+54949590200 ext. 850, ivan.huespe@hospitalitaliano.org.ar), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to recovery of kidney function (time frame: Within 30 days from ICU day 5 (Time Zero) or until ICU discharge, whichever occurs first.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07631221, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2026.