Critical Illness Myopathy and Trajectory of Recovery in AKI Requiring CRRT

University of Iowa10 enrolled

Overview

The purpose of this study is to determine whether patients with acute kidney injury requiring renal replacement therapy have a higher incidence of muscle wasting than controls and whether the course of recovery is longer compared to controls.

Acute kidney injury (AKI), the abrupt loss of kidney function, is a common complication that affects more than half of all intensive care unit (ICU) admissions, and it is associated with substantially higher rates of morbidity and mortality in both the short- and the long-term. This is especially true in patients with AKI requiring renal replacement therapy (AKI-RRT), also known as dialysis. An understudied mechanism by which AKI-RRT may contribute to poor clinical outcomes, both in the hospital and after discharge, is through its impact on muscle mass and muscle function. AKI of any severity is known to alter tissue utilization of amino acids, and preliminary data suggest that RRT in the ICU may exacerbate muscle dysfunction through the removal of large quantities of amino acids from the patient's plasma. This study will determine whether patients with AKI-RRT have greater lean muscle loss over 1 week than historical critically ill controls, whether patients with AKI-RRT have diminished recovery of muscle mass and function at 1-3 months following discharge compared to controls, and whether changes in plasma levels of amino acids during hospitalization correlate with loss of muscle function or lack of recovery.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Acute Kidney Injury Critical Illness Myopathy Dialysis; Complications

Interventions

Musculoskeletal ultrasoundDIAGNOSTIC_TEST

Ultrasound of rectus femoris to determine cross-sectional area, muscle thickness, echo intensity.

Assessments of muscle strength and physical functionDIAGNOSTIC_TEST

A battery of tests of physical function and muscle strength (see outcomes section for details).

MetabolomicsDIAGNOSTIC_TEST

Using metabolomic analysis, concentrations of amino acids and other important analytes will be measured in patient plasma and CRRT effluent

Eligibility

Sex: ALLMin age: 18 YearsMax age: 89 Years

Medical Language ↔ Plain English

Inclusion Criteria: * \>18 years old * AKI requiring CRRT, with enrollment within 48 hours of CRRT initiation Exclusion Criteria: * ICU admission for \>7 days * RRT of any kind at any time prior to ICU admission * Chronic kidney disease (CKD) with estimated glomerular filtration rate \<20 mL/min/1.73 m2 as calculated by the 2021 CKD-EPI equation * underlying muscle disorders or muscle atrophy such as quadriplegia or hemiplegia, stroke with residual motor deficits, end-stage liver disease, active alcohol use disorder, active malignancy (other than non-melanoma skin cancer) within 1 year, burns, or other baseline neuromuscular disease * pregnancy * concomitant use of other extracorporeal support devices such as ventricular assist devices or extracorporeal membrane oxygenation * anticipated inability to engage in weight-bearing testing after discharge (e.g., trauma or orthopedic surgery) * subjects will be ineligible for outpatient testing if they remain on RRT in the week prior to the research appointment

Locations (3)

University of Iowa

Iowa City, Iowa, United States

University of Kentucky

Lexington, Kentucky, United States

University of New Mexico

Albuquerque, New Mexico, United States

Outcomes

Primary Outcomes

ICU Stage: rectus femoris (RF) cross-sectional area (CSA)

RF CSA as assessed by musculoskeletal ultrasound (MSKUS) will be measured at day 0 (study enrollment within 48 hours of CRRT initiation), at day 3, and at day 7 (or at ICU discharge if before day 7).

Time frame: 7 days

ICU Stage: RF muscle thickness (mT)

RF mT as assessed by MSKUS will be measured at day 0 (study enrollment within 48 hours of CRRT initiation), at day 3, and at day 7 (or at ICU discharge if before day 7).

Time frame: 7 days

ICU Stage: RF echo intensity (EI)

RF EI as assessed by MSKUS will be measured at day 0 (study enrollment within 48 hours of CRRT initiation), at day 3, and at day 7 (or at ICU discharge if before day 7).

Time frame: 7 days

RF CSA at discharge

RF CSA as assessed by MSKUS will be measured at hospital discharge.

Time frame: 1 month

RF mT at discharge

RF mT as assessed by MSKUS will be measured at hospital discharge.

Time frame: 1 month

RF EI at discharge

RF EI as assessed by MSKUS will be measured at hospital discharge.

Time frame: 1 month

RF CSA at post-discharge outpatient visit

RF CSA as assessed by MSKUS will be measured at outpatient follow-up visit.

Time frame: 1-3 months

RF mT at post-discharge outpatient visit

RF mT as assessed by MSKUS will be measured at outpatient follow-up visit.

Data from ClinicalTrials.gov

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Time frame: 1-3 months

RF EI at post-discharge outpatient visit

RF mT as assessed by MSKUS will be measured at outpatient follow-up visit.

Time frame: 1-3 months

ICU Stage: ICU Mobility Scale

The ICU Mobility Scale is an 11-point scale ranging from 0-10 which involves scoring a patient's maximum level of mobility in the prior 24-hour period. The ICU Mobility Scale will be performed at the same 3 time points as the MSKUS assessments.

Time frame: 7 days

Muscle Strength - Medical Research Council Sum-score (MRC-ss) at discharge

MRC-ss is a measure of global peripheral muscle strength that is the current clinical standard for diagnosing ICU-acquired weakness. Muscle strength is assessed by physical exam and rated on an ordinal scale (0-5) at six bilateral muscle groups: shoulder abductors, elbow flexors, wrist extensors, hip flexors, knee extensors, and ankle dorsiflexors.

Time frame: 1 month

Muscle Strength - MRC-ss at post-discharge outpatient visit

Time frame: 1-3 months

Muscle Strength - knee extension by hand-held dynamometry (HHD) at hospital discharge

Maximal isometric knee extensor muscle strength as measured by HHD.

Time frame: 1 month

Muscle Strength - knee extension by HHD at post-discharge outpatient visit

Maximal isometric knee extensor muscle strength as measured by HHD.

Time frame: 1-3 months

Muscle Strength - Grip Strength at hospital discharge

Maximal isometric grip strength as measured by hand-grip dynamometry (HGD)

Time frame: 1 month

Muscle Strength - Grip Strength at post-discharge outpatient visit

Maximal isometric grip strength as measured by HGD

Time frame: 1-3 months

Physical Function - Short Physical Performance Battery (SPPB) at discharge

SPPB is a performance-based composite test with a total of 12 points including components of balance (side-by-side stand, semi-tandem stand, and full-tandem stand), chair-to-stand test, and 4-meter habitual gait speed used to assess physical function and physical frailty.

Time frame: 1 month

Physical Function - SPPB at post-discharge outpatient visit

Time frame: 1-3 months

TUG Test at post-discharge outpatient visit

The Timed Up and Go (TUG) test assesses the time (in seconds) for a subject to stand on command from a seated position, walk 3 meters, turn around, walk back to the chair, and sit down, thereby assessing mobility, physical function, and fall risk.

Time frame: 1-3 months

Physical Function - 6-minute walk test (6MWT) at post-discharge outpatient visit

The 6MWT assesses the distance a subject can walk in six minutes, providing a global representation of physical function and cardiopulmonary endurance.

Time frame: 1-3 months

Quality of Life testing using EuroQol Group 5-dimension 5-level (EQ-5D-5L) questionnaire at post-discharge outpatient visit

The EQ-5D-5L is a standardized measure of health status developed by the Euro-Qol Group to provide an assessment of health for clinical and economic appraisal.

Time frame: 1-3 months

Physical Function - Clinical Frailty Scale (CFS) at post-discharge outpatient visit

CFS is a widely adopted judgement-based tool to screen for frailty and to broadly stratify degrees of fitness and frailty.

Time frame: 1-3 months

Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Questionnaire at post-discharge outpatient visit

The FACIT-F scale is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function.

Time frame: 1-3 months

36-Item Short Form Health Survey Physical Function Scale (SF-36) at post-discharge outpatient visit

The SF-36 is a 36-item patient-reported survey of health commonly used to evaluate adult patients which contains 8 domains, including a physical function scale based on 10 of the 36 items which has been shown to have high reliability.

Time frame: 1-3 months

Return to driving

Yes / No outcome assessed at the outpatient follow-up visit

Time frame: 1-3 months

Return to work or hobby

Yes / No outcome assessed at the outpatient follow-up visit

Time frame: 1-3 months

Hospital Readmission

Yes / No outcome assessed at the outpatient follow-up visit

Time frame: 1-3 months

Emergency Department Visit

Yes / No outcome assessed at the outpatient follow-up visit

Time frame: 1-3 months

Secondary Outcomes

ICU Stage: Changes in Plasma Metabolome

Plasma samples will be obtained at day 0 (study enrollment within 48 hours of CRRT initiation), at day 3, and at day 7 (or at ICU discharge if before day 7) and metabolomic analysis will be performed to determine if changes in the plasma metabolome with CRRT initiation correlate with parameters of muscle wasting and/or trajectory of recovery of muscle weakness.

Time frame: 7 days

ICU Stage: Changes in CRRT Effluent Metabolome

CRRT effluent samples will be obtained at day 0 (study enrollment within 48 hours of CRRT initiation), at day 3, and at day 7 (or at ICU discharge if before day 7) and metabolomic analysis will be performed to determine if changes in the effluent metabolome with CRRT initiation correlate with parameters of muscle wasting and/or trajectory of recovery of muscle weakness.

Time frame: 7 days