Ultrasound Markers of Organ Congestion in Severe Acute Kidney Injury

Completed

• Conditions: Acute Kidney Injury; Fluid Overload; Ultrasonography
• Interventions: 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

• Registration Number: NCT04095143
• Lead Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)

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.

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 Timeline

• Study Start: 2018-09-04
• Study First Submitted: 2019-09-17
• Study First Submitted QC: 2019-09-17
• Study First Posted: 2019-09-19
• Primary Completion: 2022-01-01
• Study Completion: 2022-09-01
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-11
• Last Update Posted: 2022-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 125

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
New onset of stage ≥2 acute kidney injury	Portal vein flow	Either: 1. A ≥ 2-fold increase in serum creatinine OR 2. A serum creatinine ≥ 354 μmol/L with evidence of a minimum increase of 27 μmol/L OR 3. Urine output \< 6.0 mL/kg over the preceding 12 hours OR 4. Initiation of RRT for severe acute kidney injury less than 72 hours before recruitment
New onset of stage ≥2 acute kidney injury	Intra-renal flow	Either: 1. A ≥ 2-fold increase in serum creatinine OR 2. A serum creatinine ≥ 354 μmol/L with evidence of a minimum increase of 27 μmol/L OR 3. Urine output \< 6.0 mL/kg over the preceding 12 hours OR 4. Initiation of RRT for severe acute kidney injury less than 72 hours before recruitment
New onset of stage ≥2 acute kidney injury	Hepatic vein flow	Either: 1. A ≥ 2-fold increase in serum creatinine OR 2. A serum creatinine ≥ 354 μmol/L with evidence of a minimum increase of 27 μmol/L OR 3. Urine output \< 6.0 mL/kg over the preceding 12 hours OR 4. Initiation of RRT for severe acute kidney injury less than 72 hours before recruitment
New onset of stage ≥2 acute kidney injury	Left ventricular function	Either: 1. A ≥ 2-fold increase in serum creatinine OR 2. A serum creatinine ≥ 354 μmol/L with evidence of a minimum increase of 27 μmol/L OR 3. Urine output \< 6.0 mL/kg over the preceding 12 hours OR 4. Initiation of RRT for severe acute kidney injury less than 72 hours before recruitment
New onset of stage ≥2 acute kidney injury	Pulmonary B-lines	Either: 1. A ≥ 2-fold increase in serum creatinine OR 2. A serum creatinine ≥ 354 μmol/L with evidence of a minimum increase of 27 μmol/L OR 3. Urine output \< 6.0 mL/kg over the preceding 12 hours OR 4. Initiation of RRT for severe acute kidney injury less than 72 hours before recruitment
New onset of stage ≥2 acute kidney injury	Dimensions of the inferior vena cava	Either: 1. A ≥ 2-fold increase in serum creatinine OR 2. A serum creatinine ≥ 354 μmol/L with evidence of a minimum increase of 27 μmol/L OR 3. Urine output \< 6.0 mL/kg over the preceding 12 hours OR 4. Initiation of RRT for severe acute kidney injury less than 72 hours before recruitment
New onset of stage ≥2 acute kidney injury	Right ventricular function	Either: 1. A ≥ 2-fold increase in serum creatinine OR 2. A serum creatinine ≥ 354 μmol/L with evidence of a minimum increase of 27 μmol/L OR 3. Urine output \< 6.0 mL/kg over the preceding 12 hours OR 4. Initiation of RRT for severe acute kidney injury less than 72 hours before recruitment

Primary Outcome Measures

Name	Time	Method
Number of participants with major adverse kidney events at 30 days	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

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

Trial Locations

Locations (6)

University of Alberta; 🇨🇦 Edmonton, Alberta, Canada

Centre Hospitalier de l'Université de Montréal; 🇨🇦 Montréal, Quebec, Canada

University of Kentucky; 🇺🇸 Lexington, Kentucky, United States

Montreal Heart Institute; 🇨🇦 Montreal, Quebec, Canada

Sunnybrook Health Science Centre; 🇨🇦 Toronto, Ontario, Canada

St. Michael's hospital; 🇨🇦 Toronto, Ontario, Canada