Critical Illness Myopathy and Trajectory of Recovery in AKI Requiring CRRT

Critical Illness Myopathy and Trajectory of Recovery in Acute Kidney Injury (AKI) Requiring Continuous Renal Replacement Therapy (CRRT): A Prospective Observational Trial

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Kidney Injury; Critical Illness Myopathy; Dialysis; Complications
• Intervention / Treatment: Diagnostic test: Musculoskeletal ultrasound; Diagnostic test: Assessments of muscle strength and physical function; Diagnostic test: Metabolomics

Detailed Description

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 (Actual): 10

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa
  • Kentucky
    • Lexington, Kentucky, United States, 40506
      • University of Kentucky
  • New Mexico
    • Albuquerque, New Mexico, United States, 87106
      • University of New Mexico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will be composed of critically ill patients with acute kidney injury requiring continuous renal replacement therapy in an ICU setting.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
AKI-RRT; Adults admitted to the ICU with AKI requiring CRRT with study enrollment within 48 hours of CRRT initiation.	Diagnostic test: Musculoskeletal ultrasound; Ultrasound of rectus femoris to determine cross-sectional area, muscle thickness, echo intensity.; Diagnostic test: Assessments of muscle strength and physical function; A battery of tests of physical function and muscle strength (see outcomes section for details).; Diagnostic test: Metabolomics; Using metabolomic analysis, concentrations of amino acids and other important analytes will be measured in patient plasma and CRRT effluent
Historical Controls; The controls for the ICU phase will be 41 critically ill adults without AKI-RRT in whom similar measurements of muscle size, quality, and function were collected in a recent prior study [PubMed ID: 33148301]. The controls for the recovery phase will come from an ongoing prospective observational study being performed at the University of Kentucky, which will include outpatient functional assessments performed on 200 ICU survivors (NCT05537298).	Diagnostic test: Musculoskeletal ultrasound; Ultrasound of rectus femoris to determine cross-sectional area, muscle thickness, echo intensity.; Diagnostic test: Assessments of muscle strength and physical function; A battery of tests of physical function and muscle strength (see outcomes section for details).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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).	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).	7 days
RF CSA at discharge	RF CSA as assessed by MSKUS will be measured at hospital discharge.	1 month
RF mT at discharge	RF mT as assessed by MSKUS will be measured at hospital discharge.	1 month
RF EI at discharge	RF EI as assessed by MSKUS will be measured at hospital discharge.	1 month
RF CSA at post-discharge outpatient visit	RF CSA as assessed by MSKUS will be measured at outpatient follow-up visit.	1-3 months
RF mT at post-discharge outpatient visit	RF mT as assessed by MSKUS will be measured at outpatient follow-up visit.	1-3 months
RF EI at post-discharge outpatient visit	RF mT as assessed by MSKUS will be measured at outpatient follow-up visit.	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.	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.	1 month
Muscle Strength - MRC-ss at post-discharge outpatient visit	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.	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.	1 month
Muscle Strength - knee extension by HHD at post-discharge outpatient visit	Maximal isometric knee extensor muscle strength as measured by HHD.	1-3 months
Muscle Strength - Grip Strength at hospital discharge	Maximal isometric grip strength as measured by hand-grip dynamometry (HGD)	1 month
Muscle Strength - Grip Strength at post-discharge outpatient visit	Maximal isometric grip strength as measured by HGD	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.	1 month
Physical Function - SPPB at post-discharge outpatient visit	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.	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.	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.	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.	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.	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.	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.	1-3 months
Return to driving	Yes / No outcome assessed at the outpatient follow-up visit	1-3 months
Return to work or hobby	Yes / No outcome assessed at the outpatient follow-up visit	1-3 months
Hospital Readmission	Yes / No outcome assessed at the outpatient follow-up visit	1-3 months
Emergency Department Visit	Yes / No outcome assessed at the outpatient follow-up visit	1-3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	7 days

Collaborators and Investigators

• Sponsor: University of Iowa

Publications and helpful links

General Publications

• Mayer KP, Thompson Bastin ML, Montgomery-Yates AA, Pastva AM, Dupont-Versteegden EE, Parry SM, Morris PE. Acute skeletal muscle wasting and dysfunction predict physical disability at hospital discharge in patients with critical illness. Crit Care. 2020 Nov 4;24(1):637. doi: 10.1186/s13054-020-03355-x.
• Mayer KP, Welle MM, Evans CG, Greenhill BG, Montgomery-Yates AA, Dupont-Versteegden EE, Morris PE, Parry SM. Muscle Power is Related to Physical Function in Patients Surviving Acute Respiratory Failure: A Prospective Observational Study. Am J Med Sci. 2021 Mar;361(3):310-318. doi: 10.1016/j.amjms.2020.09.018. Epub 2020 Oct 3.
• Mayer KP, Dhar S, Cassity E, Denham A, England J, Morris PE, Dupont-Versteegden EE. Interrater Reliability of Muscle Ultrasonography Image Acquisition by Physical Therapists in Patients Who Have or Who Survived Critical Illness. Phys Ther. 2020 Aug 31;100(9):1701-1711. doi: 10.1093/ptj/pzaa068.
• Mayer KP, Ortiz-Soriano VM, Kalantar A, Lambert J, Morris PE, Neyra JA. Acute kidney injury contributes to worse physical and quality of life outcomes in survivors of critical illness. BMC Nephrol. 2022 Apr 7;23(1):137. doi: 10.1186/s12882-022-02749-z.
• Teixeira JP, Mayer KP, Griffin BR, George N, Jenkins N, Pal CA, Gonzalez-Seguel F, Neyra JA. Intensive Care Unit-Acquired Weakness in Patients With Acute Kidney Injury: A Contemporary Review. Am J Kidney Dis. 2023 Mar;81(3):336-351. doi: 10.1053/j.ajkd.2022.08.028. Epub 2022 Nov 2.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2021
• Primary Completion (Actual): September 30, 2023
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: October 20, 2021
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 18, 2022

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Kidney Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Musculoskeletal Diseases; Neuromuscular Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Critical Illness; Acute Kidney Injury; Muscular Diseases
• Other Study ID Numbers: 202002328

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No