Ultrasound Markers of Organ Congestion in Severe Acute Kidney Injury (ECHO-AKI)

• ClinicalTrials.gov Identifier: NCT04095143
• Recruitment Status: Completed
• First Posted: September 19, 2019
• Last Update Posted: November 14, 2022
• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
• Collaborators: Unity Health Toronto; Sunnybrook Health Sciences Centre; University of Kentucky; University of Alberta; Montreal Heart Institute
• Information provided by (Responsible Party): Centre hospitalier de l'Université de Montréal (CHUM)

Study Description

Brief Summary:

Fluid overload is associated with adverse outcomes in patients with severe acute kidney injury. It remains unclear if fluid overload is merely a marker of disease severity or if organ congestion is a mediator of complications. Point-of-care ultrasound could be a modality used to assess organ congestion and its clinical implications. The objective of this study is to determine whether ultrasound markers of organ congestion are associated with major adverse kidney events in critically ill patients with severe acute kidney injury.

Condition or disease	Intervention/treatment
Acute Kidney Injury; Fluid Overload; Ultrasonography	Diagnostic Test: Portal vein flow; Diagnostic Test: Intra-renal flow; Diagnostic Test: Hepatic vein flow; Diagnostic Test: Pulmonary B-lines; Diagnostic Test: Dimensions of the inferior vena cava; Diagnostic Test: Left ventricular function; Diagnostic Test: Right ventricular function

Detailed Description:

Background: Fluid overload is associated with adverse outcomes in patients with severe acute kidney injury. It remains unclear if fluid overload is merely a marker of disease severity or if organ congestion is a direct mediator of complications. Point-of-care ultrasound could be a modality used to assess organ congestion and its clinical implications.

Objective: To determine whether ultrasound markers of organ congestions are associated with major adverse kidney events and other adverse clinical outcomes.

Study design: A cohort of critically ill patients with a new onset of severe acute kidney injury will undergo repeated ultrasound assessments to detect the presence of the following markers:

• Portal flow pulsatility on pulse-wave Doppler
• Discontinuous intra-renal venous flow on pulse-wave Doppler
• Abnormal hepatic vein waveform on pulse wave Doppler
• Presence of pulmonary B-line artifacts on 2D lung ultrasound
• Presence of dilated and non-collapsible inferior vena cava on 2D ultrasound
• Presence of systolic right ventricular dysfunction
• Presence of systolic left ventricular dysfunction

Clinical outcomes will be collected for up to 90 days after recruitment.

Perspective: An approach targeting the resolution of organ congestion might improve the prognosis in patients with severe acute kidney injury. Identifying clinically relevant markers of organ congestion is a precursor to the design of future interventional trials investigating personalized fluid balance management.

Study Design

• Study Type: Observational
• Actual Enrollment: 125 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Ultrasound Markers of Organ Congestion in Severe Acute Kidney Injury
• Actual Study Start Date: September 4, 2018
• Actual Primary Completion Date: January 1, 2022
• Actual Study Completion Date: September 1, 2022

Groups and Cohorts

Group/Cohort

Intervention/treatment

New onset of stage ≥2 acute kidney injury; Either: A ≥ 2-fold increase in serum creatinine OR; A serum creatinine ≥ 354 μmol/L with evidence of a minimum increase of 27 μmol/L OR; Urine output < 6.0 mL/kg over the preceding 12 hours OR; Initiation of RRT for severe acute kidney injury less than 72 hours before recruitment

Diagnostic Test: Portal vein flow; Doppler assessment performed on day 0, 3 and 7.; Diagnostic Test: Intra-renal flow; Doppler assessment performed on day 0, 3 and 7.; Diagnostic Test: Hepatic vein flow; Doppler assessment performed on day 0, 3 and 7.; Diagnostic Test: Pulmonary B-lines; Ultrasound assessment of performed on day 0, 3 and 7.; Diagnostic Test: Dimensions of the inferior vena cava; Ultrasound assessment of performed on day 0, 3 and 7.; Diagnostic Test: Left ventricular function; Ultrasound assessment of performed on day 0, 3 and 7.; Diagnostic Test: Right ventricular function; Ultrasound assessment of performed on day 0, 3 and 7.

Outcome Measures

Primary Outcome Measures :

1. Number of participants with major adverse kidney events at 30 days [ Time Frame: 30 days ]
   Either death, receipt of renal replacement therapy or sustained loss of kidney function (new onset of estimated glomerular filtration rate (eGFR) < 60 or, if pre-existing eGFR < 60, 25% or greater decline in eGFR)

Secondary Outcome Measures :

1. Rate of in-hospital death [ Time Frame: 30 days ]
   All cause mortality during hospital stay
2. Number of participants with renal replacement therapy dependence at 30 days [ Time Frame: 30 days ]
   Receipt of renal replacement therapy at 30 days from enrollment
3. Number of participants with sustained loss of kidney function at 30 days [ Time Frame: 30 days ]
   New onset of estimated glomerular filtration rate (eGFR) < 60 or, if pre-existing eGFR < 60, 25% or greater decline in eGFR)
4. Ventilation-free days through day 30 [ Time Frame: 30 days ]
   A ventilator-free day will be defined as the receipt of < 2 hours of either invasive or non-invasive ventilation within a 24-hour period.
5. Intensive care unit (ICU)-free days through day 30 [ Time Frame: 30 days ]
   An ICU-free day will be defined as admission to an ICU for < 2 hours within a 24 hours period.
6. Vasopressor-free days though day 30 [ Time Frame: 30 days ]
   Vasopressor will include norepinephrine, epinephrine, vasopressin and phenylephrin
7. Number of participants with major adverse kidney events at 90 days [ Time Frame: 90 days ]
   Either death, receipt of renal replacement therapy or sustained loss of kidney function (estimated glomerular filtration rate (eGFR) < 60 or, if pre-existing eGFR < 60, 25% or greater decline in eGFR)
8. Rate of death at 90 days [ Time Frame: 90 days ]
   All cause mortality at 90 days
9. Estimated glomerular filtration rate at 90 days [ Time Frame: 90 days ]
   Calculated with the CKD-EPI equation (92) with serum creatinine from a sample drawn as close as possible to Day 90.

Other Outcome Measures:

1. Hemodynamic instability during renal replacement therapy [ Time Frame: 7 days ]
   Intradialytic hypotension (MAP<65 mmHg) requiring one or more of the following interventions: interruption of fluid removal, introduction of norepinephrine or increase in its dose of more than 25%, administration of volume expansion or interruption of RRT within 8 hours after initiating net negative fluid balance.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• Sampling Method: Non-Probability Sample

Study Population

Critically ill adult patients with severe acute kidney injury

Criteria

Inclusion Criteria:

• Age ≥ 18 years
• Admitted to the ICU
• Women with serum creatinine ≥ 100 µmol/L and men with serum creatinine ≥ 130 µmol/L
• Severe acute kidney injury (AKI) defined either: A ≥ 2-fold increase in serum creatinine from a known pre-morbid baseline or during the current hospitalization OR achievement of a serum creatinine ≥ 354 µmol/L with evidence of a minimum increase of 27 µmol/L from pre-morbid baseline or during the current hospitalization OR Urine output < 6.0 mL/kg over the preceding 12 hours OR initiation of renal replacement therapy (RRT) for severe AKI initiated less than 72 hours before recruitment.

Exclusion Criteria:

• Lack of commitment to provide RRT as part of limitation of ongoing life support. (Operational definition: Critical care team has deemed the patient not to be eligible for escalation of life support, including the initiation of RRT, or substitute decision makers have declined offer of same.)
• Known pre-hospitalization advanced chronic kidney disease, defined by an estimated glomerular filtration rate < 20 mL/min/1.73 m2 in a patient who is not on chronic RRT. (Operational definition: The coordinator will review all documented serum creatinine values within 365 days prior to the date of admission for the current hospitalization. The value closest to the admission date will be considered as the "baseline" and will be used to calculate the corresponding estimated glomerular filtration rate using an online calculator. A value of < 20 mL/min/1.73 m2 derived from the CKD-EPI equation will be grounds for exclusion.

Contacts and Locations

Locations

United States, Kentucky

University of Kentucky

Lexington, Kentucky, United States, 40506

Canada, Alberta

University of Alberta

Edmonton, Alberta, Canada

Canada, Ontario

Sunnybrook Health Science Centre

Toronto, Ontario, Canada, M4N 3M5

St. Michael's hospital

Toronto, Ontario, Canada, M5B 1W8

Canada, Quebec

Montreal Heart Institute

Montreal, Quebec, Canada

Centre Hospitalier de l'Université de Montréal

Montréal, Quebec, Canada, H1X 2B9

Sponsors and Collaborators

Centre hospitalier de l'Université de Montréal (CHUM)

Unity Health Toronto

Sunnybrook Health Sciences Centre

University of Kentucky

University of Alberta

Montreal Heart Institute

Investigators

• Principal Investigator: William Beaubien-Souligny, MD; CHUM

More Information

• Responsible Party: Centre hospitalier de l'Université de Montréal (CHUM)
• ClinicalTrials.gov Identifier: NCT04095143
• Other Study ID Numbers: MP-02-2020-8578 (MP)
• First Posted: September 19, 2019
• Last Update Posted: November 14, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre hospitalier de l'Université de Montréal (CHUM):

Point-Of-Care ultrasound; Doppler; Major adverse kidney events; Portal flow pulsatility; IVC ultrasound; Cardiac ultrasound; Right ventricular failure; Intensive care

Additional relevant MeSH terms:

Acute Kidney Injury; Wounds and Injuries; Renal Insufficiency; Kidney Diseases; Urologic Diseases