Novel Assessment of Viscoelastic Skeletal Muscle Properties in Chronic Kidney Disease: Association with Physical Functioning

Abstract

Chronic kidney disease (CKD) is characterised by poor physical function. Mechanical muscle properties such as tone, elasticity, and stiffness influence the functional state of the muscle. Measuring these muscle mechanical properties is difficult and data on CKD are sparse. Using a novel myotonometer device, the aims of this study were to compare the viscoelastic muscle properties in CKD patients with previously reported data and to explore the association with muscle function. Non-dialysis-dependent CKD participants were recruited into a cross-sectional study conducted between 2018 and 2020. Muscle properties (tone, stiffness, elasticity) were assessed using a myotonometer (MyotonPRO). Muscle function was assessed using physical performance tests (sit-to-stand 5 and 60, timed up and go, short physical performance battery, gait speed, incremental shuttle walk, postural sway). General linear regression models were used to explore the association between muscle properties and physical function. Thirty-nine participants were included (age 64.2 (SD: 10.4) years; 51% male; eGFR 40.9 (SD: 20.0) mL/min/1.73 m²). Participants with CKD had reduced muscle tone, stiffness, and elasticity compared to previously reported studies. Muscle tone (B = −0.567, p = 0.003) and muscle stiffness (B = −0.368, p = 0.071) were greater in males than females. Increased BMI was associated with lower muscle tone (B = −0.528, p = 0.002) and muscle stiffness (B = −0.577, p = 0.002). No meaningful nor consistent associations were found between these properties and measures of muscle function and physical performance. In conclusion, using a novel handheld myotonometer, this study found that CKD patients exhibit a reduction in muscle tone, stiffness, and elasticity. In a passive state, these viscoelastic muscle properties showed no consistent associations with physical performance.

1. Introduction

People living with chronic kidney disease (CKD) are characterised by poor physical function, which is associated with increased morbidity and mortality risk [1,2]. These reductions in physical functioning are partly driven by the accelerated adverse changes to skeletal muscle observed in CKD; these include a reduction in muscle size and strength (ability to generate force) [2,3,4], increased intramuscular infiltration of adiposity and fibrosis [3], and metabolic dysfunction such as increased inflammation and mitochondrial dysregulation [5]. The skeletal muscles are organized multi-nucleated myofibers whose function is to generate length and velocity-dependent forces for movement or stability, and their function depends on their intrinsic properties and extrinsic arrangement [6]. Mechanical muscle properties can be used to describe the mechanical firmness that exists when skeletal muscles are in a steady-state condition with no voluntary contraction [7]. These properties include components such as tone, elasticity, and stiffness [8] and quantify the functional state of the muscle [9].

Muscle tone (residual muscle tension or tonus) is the continuous and passive partial contraction of the muscles or a muscle’s resistance to passive stretch during the resting state. The resting muscle tone is derived from the viscoelastic properties of the soft tissues associated with the muscle [10] and is controlled by the sensory muscle spindle. The functional roles of passive muscle tone are maintaining balance, stability, and posture. Muscle tone also provides adequate blood circulation to the muscle and improves energy efficiency during prolonged work duration without fatigue [11,12]. Excessive muscle tone disrupts blood supply to the muscle, which diminishes oxygen transportation; this may lead to increased pain and poorer motor performance [11]. Muscle elasticity describes a muscle’s ability to restore its original shape following contraction; this is inversely proportional to the decrement [11]. Muscle elasticity is vital in increasing blood circulation during muscular contractions. Reductions in muscle elasticity increase fatigability and reduce any speed of movement [11]. Muscle stiffness is defined as a muscle’s ability to resist the deformation caused by external forces [12,13]. The stiffness of the antagonist muscle is associated with the speed and ease of movement performed by the agonist muscle. When the stiffness of a muscle increases, a greater force is needed from the antagonist; this decreases the energy expenditure economy of movement [11].

Measuring changes in these different muscle mechanical properties remains a challenge. Several methods are available including subjective grading through palpation (e.g., the Ashworth Scale), muscle deformation using ultrasound, dynamometry, and ramp-and-hold and pendulum tests [11,14,15]. These methods, particularly ones that require subjective scaling and assessment or voluntary effort from the participant, are prone to bias and poor reliability [14,16]. Alternatively, the MyotonPRO is a commercially available handheld device that can measure muscle mechanical properties non-invasively and objectively. Whilst the effects of CKD on muscle mass and strength are well recognised, the characteristics of mechanical muscle properties have been less well documented. A preliminary study on stable chronic haemodialysis (HD) patients by Kanafa et al. [17] investigated changes in muscle properties using the MyotonPRO during dialysis and a functional performance task. However, it remains unknown which of the properties described best reflect skeletal muscle health or the role they have in people with CKD. Understanding the mechanical properties of muscles could be significant in monitoring the pathologic processes of muscles, as well as assessing the efficacy of interventions.

The aims of this study were four-fold: (1) to compare the viscoelastic muscle properties of CKD patients with previously reported healthy and clinical participants; (2) to investigate the association of demographic and clinical characteristics with viscoelastic muscle properties; (3) to explore the association of passive skeletal muscle viscoelastic properties with physical functioning and postural stability; and (4) to determine the association of asymmetry % in skeletal muscle viscoelastic properties between dominant and non-dominant sides with physical functioning and postural stability.

2. Results

2.1. Participant Demographic and Clinical Characteristics

Participant characteristics can be found in

Table 1. Basic participant demographic and clinical characteristics.

	N = 39
Age (years)	64.2 (SD: 10.4)
Sex (male, n (%))	20 (51%)
Ethnicity (n, %)
White	35 (88%)
Asian	1 (3%)
Other	1 (3%)
Diabetes (n, %)	8 (21%)
eGFR (mL/min/1.73 m2)	40.9 (SD: 20.0)
Haemoglobin (g/L)	128.9 (SD: 18.0)
Albumin (g/L)	43.1 (SD: 2.6)
Body mass index (kg/m2)	29.3 (SD: 4.9)

Data shown as mean and standard deviation (SD). eGFR = Estimated glomerular filtration rate.

. In summary, data from 39 participants with CKD were analysed. The mean age was 64.2 (SD: 10.4) years and over half (51%) of the cohort was male. The mean eGFR was 40.9 (SD: 20.0) mL/min/1.73 m² with a mean albumin of 43.1 (SD: 2.6) g/L.

2.2. Aim 1: Compare the Viscoelastic Muscle Properties of CKD Patients with Previously Reported Healthy and Clinical Participants

Table 2. Viscoelastic muscle properties for rectus femoris assessed using MyotonPRO compared to other selected studies.

Study	Condition	Characteristics of Participants Included	Muscle Tone, Hz		Muscle Stiffness, Nm		Muscle Elasticity, log *
			Dom.	Non-D	Dom.	Non-D	Dom.	Non-D
This study	CKD	N = 39 adults with CKD; age 64 years; BMI 29.3 kg/m2	12.4	12.7	238.0	253.4	4.6	1.8
Chang, 2021 [18]	Knee OA at 90°	N = 25 adults with knee OA; age 62.2 years; BMI 24.2 kg/m2	-	-	292.5↑		-	-
Aird, 2012 [7]	Healthy a	N = 20 older adults; age 72 years; BMI 25.2 kg/m2	16.1↑	15.7↑	318.8↑	310.8↑	1.7↓	1.7↓
Agyapong-Badu, 2016 [19]	Healthy Sedentary b	N = 61 younger adults; age (males 25; females, 27 years); BMI (males 23.2, females 22.9 kg/m2)	Males: 16.4↑ Females: 13.6↑		Males: 292↑ Females: 233↓		Males: 1.3↓ Females: 1.2↓
		N = 62 older adults; age (males 74; females, 76 years); BMI (males 25.9 females 25.6 kg/m2)	Males: 16.7↑ Females: 14.9↑		Males: 328↑ Females: 311↑		Males: 1.6↓ Females: 1.6↓
Mullix, 2012 [20]	Healthy c	N = 21 younger adults; age 26 years; BMI 23.9 kg/m2	15.5↑		276↑		1.32↓
Ko, 2018 [15]	Complete SCI	N = 13 males with complete SCI (age 54 years)	18.6↑	18.5↑	410.3↑	407.5↑	1.4↓	1.3↓
Chen, 2019 [21]	Healthy d Sedentary	N = 30 younger adults; age 25 years; BMI 21.0 kg/m2	14.9↑	15.0↑	268.5↑	269.1↑	Not reported	Not reported
Kocaer, 2021 [22]	Healthy	N = 109 older adults, age 71 years; BMI 28 kg/m2	13.0↑	13.0↑	225↓	228↓	1.46↓	1.43↓
Kanafa, 2019 [17]	HD	N = 30 adults aged 51–82 years	15.6↑		326↑		1.8↓
Conclusion			Muscle tone is ↓ in CKD		Muscle stiffness is ↓ in CKD		Muscle elasticity is ↓ in CKD

^a defined as no uncontrolled medical conditions; ^b defined as sedentary or only moderately active; ^c defined as no history of neurological or musculoskeletal disorders, back or lower limb injuries such as fractures, or pain that restricted activity for more than one week. They were permitted to undertake vigorous physical activity up to three times per week; ^d defined as no musculoskeletal dysfunction or systemic diseases, and they did not perform intense exercises or play sports weekly; * higher value indicates reduced elasticity. D/Dom. = Dominant (side); OA = Osteoarthritis; SCI = Spinal cord injury; HD = Haemodialysis. Arrows indicate difference compared to the CKD group from the current study.

shows viscoelastic muscle properties for the rectus femoris assessed using a MyotonPRO in our cohort compared to other selected studies. Overall, our group of CKD patients had notably reduced muscle tone, stiffness, and elasticity in comparison to that reported previously in non-CKD populations.

2.3. Aim 2: Investigate the Association of Demographic and Clinical Characteristics with Viscoelastic Muscle Properties

Muscle tone (β = −0.567, p = 0.003) and muscle stiffness (β = −0.368, p = 0.071) were greater in males than females. Increased BMI was associated with lower muscle tone (β = −0.528, p = 0.002) and muscle stiffness (β = −0.577, p = 0.002). Age, eGFR, Hb, and albumin had no association with any of the muscle properties (

Table 3. Association of demographic and clinical characteristics with viscoelastic muscle properties.

	Muscle Tone, Hz			Muscle Stiffness, Nm			Muscle Elasticity, log
	β	t	p	β	t	p	β	t	p
Age (years)	0.045	0.305	0.763	0.002	0.011	0.991	0.066	0.341	0.736
Sex	−0.567	−3.220	0.003 *	−0.368	−1.886	0.071	−0.027	−0.117	0.908
eGFR (mL/min/1.73 m2)	−0.139	−0.845	0.406	−0.139	−0.767	0.450	−0.241	−1.107	0.279
Haemoglobin (g/L)	0.128	0.639	0.528	0.070	0.316	0.755	−0.221	−0.860	0.398
Albumin (g/L)	−0.188	−1.280	0.212	−0.210	−1.289	0.209	−0.086	−0.440	0.664
Body mass index (kg/m2)	−0.528	−3.469	0.002 *	−0.577	−3.424	0.002 *	−0.081	−0.399	0.694

β = standardised beta. * Significance recognised p < 0.050.

).

2.4. Aim 3: Explore the Association of Passive Skeletal Muscle Viscoelastic Properties with Physical Functioning and Postural Stability

In an unadjusted model, lower muscle elasticity was associated with poorer STS−60 performance (β = −0.410, p = 0.020). When adjusted for age, sex, eGFR, and muscle size, lower muscle elasticity was most predictive of poor STS−60 performance (β = −0.397, p = 0.059) and greater postural sway velocity (β = 0.289, p = 0.089). Higher muscle tone predicted a greater total SPPB score (β = 0.341, p = 0.065) in an adjusted model. However, none of these results were significant (

Table 4. Association of passive skeletal muscle viscoelastic properties with physical functioning and postural stability.

	Muscle Tone, Hz			Muscle Stiffness, Nm			Muscle Elasticity, log
	β	t	p	β	t	p	β	t	p
Model 1: Unadjusted
STS−60 (reps)	−0.016	−0.089	0.930	−0.142	−0.798	0.431	−0.410	−2.464	0.020 *
TUAG (seconds)	−0.052	−0.299	0.767	−0.027	−0.152	0.880	0.174	1.002	0.324
SPPB score (AU)	0.236	1.459	0.153	0.239	1.477	0.148	0.029	0.168	0.868
Gait speed (m/s)	0.051	0.291	0.773	0.014	0.078	0.938	−0.223	−1.295	0.205
STS−5 (seconds)	0.057	0.324	0.748	0.074	0.422	0.676	0.182	1.030	0.311
ISWT (metres)	0.137	0.731	0.471	0.043	0.230	0.820	−0.283	−1.533	0.137
Sway area (mm2)	0.184	0.991	0.330	−0.020	−0.108	0.914	−0.003	−0.018	0.986
Sway velocity (mm/s)	0.008	0.043	0.966	−0.014	−0.073	0.942	0.282	1.553	0.132
Model 2: Adjusted ¥
STS−60 (reps)	0.003	0.013	0.990	−0.128	−0.649	0.522	−0.397	−1.977	0.059
TUAG (seconds)	−0.161	−0.801	0.430	−0.077	−0.419	0.678	0.098	0.532	0.599
SPPB score (AU)	0.341	1.912	0.065	0.269	1.625	0.114	0.110	0.640	0.527
Gait speed (m/s)	0.082	0.395	0.695	0.022	0.119	0.906	−0.166	−0.894	0.379
STS−5 (seconds)	−0.052	−0.254	0.801	−0.020	−0.104	0.918	0.019	0.095	0.925
ISWT (metres)	0.130	0.613	0.546	0.014	0.073	0.943	−0.204	−1.020	0.318
Sway area (mm2)	−0.143	−0.750	0.460	−0.175	−1.032	0.312	0.005	0.028	0.978
Sway velocity (mm/s)	−0.117	−0.616	0.544	−0.029	−0.169	0.867	0.289	1.772	0.089

β = standardised beta. ¥ Model adjusted for age, sex, and eGFR and muscle (rectus femoris) cross-sectional area (CSA). * Significance recognised p < 0.050.

).

2.5. Aim 4: Determine the Association of Asymmetry % in Skeletal Muscle Viscoelastic Properties between Dominant and Non-Dominant Sides with Physical Functioning and Postural Stability

In an adjusted model, greater muscle stiffness asymmetry was associated with poorer STS−5 (β = 2.105, p = 0.045) performance and lower postural sway velocity (β = −2.106, p = 0.047). In an unadjusted model, greater muscle elasticity asymmetry was associated with greater postural sway area (β = 0.408, p = 0.035) (adjusted model, β = 0.292, p = 0.077). Asymmetric muscle tone was associated with a greater SPPB score (p = 0.080). Asymmetric muscle elasticity was associated with a quicker gait speed although not significant (p = 0.070) (

Table 5. Association of asymmetry % in skeletal muscle viscoelastic properties between dominant and non-dominant sides with physical functioning and postural stability.

	Muscle Tone Asymmetry %			Muscle Stiffness Asymmetry %			Muscle Elasticity Asymmetry %
	β	t	p	β	t	p	β	t	p
Model 1: Unadjusted
STS-60 (reps)	−0.060	−0.324	0.748	−0.144	−0.786	0.438	0.177	0.970	0.340
TUAG (seconds)	0.177	0.986	0.332	0.173	0.962	0.344	−0.228	−1.285	0.209
SPPB score (AU)	0.042	0.237	0.814	−0.089	−0.506	0.616	0.054	0.298	0.767
Gait speed (m/s)	−0.061	−0.337	0.739	−0.041	−0.223	0.825	0.297	1.706	0.098
STS-5 (seconds)	0.324	1.876	0.070	0.366	2.157	0.039 *	0.106	0.582	0.565
ISWT (metres)	−0.338	−1.829	0.079	−0.282	−1.500	0.146	0.181	0.940	0.356
Sway area (mm2)	−0.031	−0.155	0.878	0.065	0.328	0.746	0.408	2.236	0.035 *
Sway velocity (mm/s)	−0.048	−0.241	0.811	−0.112	−0.595	0.577	−0.052	−0.260	0.797
Model 2: Adjusted ¥
STS-60 (reps)	0.000	−0.001	0.999	−0.113	−0.576	0.570	0.223	1.126	0.271
TUAG (seconds)	0.171	0.861	0.397	0.165	0.866	0.394	−0.304	−1.617	0.118
SPPB score (AU)	0.102	0.540	0.593	−0.057	−0.310	0.759	0.083	0.457	0.651
Gait speed (m/s)	−0.032	−0.157	0.877	−0.020	−0.103	0.918	0.351	1.892	0.070
STS-5 (seconds)	0.321	1.745	0.093	0.363	2.105	0.045 *	0.040	0.209	0.836
ISWT (metres)	−0.216	−1.150	0.262	−0.190	−1.027	0.316	0.252	1.352	0.190
Sway area (mm2)	−0.150	−0.847	0.406	0.010	0.057	0.955	0.292	1.861	0.077
Sway velocity (mm/s)	−0.283	−1.636	0.117	−0.340	−2.106	0.047 *	−0.186	−1.103	0.282

β = standardised beta. ¥ Model adjusted for age, sex, and eGFR and muscle (rectus femoris) cross-sectional area (CSA). * Significance recognised p < 0.050.

).

3. Discussion

In this study, we present data investigating the objective viscoelastic muscle properties of CKD patients using a novel handheld myotonometer, the MyotonPRO. We found that individuals with CKD exhibit reductions in muscle tone, stiffness, and elasticity compared to previous studies of healthy younger and older adults, and those with various health conditions. These viscoelastic muscle properties showed no meaningful nor consistent associations with muscle function and physical performance.

In clinical practice, objective evaluation of muscle viscoelastic properties and function is thought to be relevant to evaluate the treatment effect and to assess the progression of pathology. Abnormal mechanical properties of the muscles have previously been thought to contribute to functional limitations and reduced mobility [8], and in CKD specifically, identifying the causes of poor muscle function may help tailor interventions and treatment. To our knowledge, the only other investigation into these properties in those with reduced kidney function using the MyotonPRO is that of Kanafa et al. [17], who reported preliminary findings in 30 chronic haemodialysis (HD) patients. They found muscle stiffness was greater and elasticity lower before HD, although tone did not change significantly. Differences in the change in stiffness were observed during a physical function test (30 s sit-to-stand).

A muscle’s resistance to passive stretch during the resting state is termed muscle tone. It is an essential feature of a healthy and well-functioning muscle [23] and is important in the maintenance of balance, stability, and posture [11,12]. Resting muscle tone is derived from the viscoelastic properties of the muscle [10] and reduced muscle tone results in reduced muscle efficiency and weakening of the muscle function [24]. Crudely, we found that our cohort of CKD patients exhibited reduced muscle tone of the rectus femoris compared to that observed in healthy older and younger adults [7,19,20,21,25], as well as other clinical conditions such as spinal cord injury and HD [15,17,18]. One might expect an increase in muscle tone in CKD patients, particularly when compared to younger adults, and as expected with ageing-related or pathological changes in muscle structure. Comparing our findings with other selected studies provides a broad overview of how our data fit into the context of the literature, however, our data are limited and should be viewed with caution. A possible explanation for any deviating findings is likely a difference in participant characteristics (e.g., BMI) and experimental protocols between studies.

Muscle stiffness is a muscle’s ability to resist the deformation caused by external forces [12,13]. As stiffness increases, muscle elasticity decreases. Elasticity describes the ability of a muscle to restore its initial shape after contraction [11]. Decreased muscle elasticity brings on easier fatigability and limited speed of movement [11]. Increased muscle stiffness (and thus lower elasticity) has been observed in ageing muscle [19] with increased collagen-content-related [26] architectural alterations, e.g., in pennation angle and fascicle length, affecting the length–tension curve [27] likely partly responsible. Muscle strength of upper extremity muscles has been shown to be related to muscle stiffness in chronic stroke patients, albeit modestly [16], and generally, the literature has found evidence linking greater stiffness values to enhanced sprinting or jumping, mainly lower body actions [28,29], as well as force development in older adults [30]. However, like muscle tone, we found no association between stiffness and elasticity with muscle function as assessed using a battery of performance tests. Using relative differences between sides (asymmetry) also showed no effect.

A probable explanation for the lack of association between these muscle properties and physical performance is that passive muscle properties in the relaxed state do not represent functional evaluation during the contracted state (i.e., during dynamic tasks) [16]. In support of our results, previous research has shown relatively poor correlations between viscoelastic variables and objective muscle properties (muscle thickness and isometric strength) in chronic stroke patients with limited hypertonia [31]. Similar findings have also been reported elsewhere [32,33], including in adults with knee osteoarthritis where muscle stiffness of the rectus femoris was not associated with disability [18] and in those with neuromuscular disorders [34]. The concurrent measurement of muscle properties in relaxation and under contraction with a myotonometer and electromyography or dynamometer is suggested for future studies.

This study presents the first data on viscoelastic properties in CKD patients using the MyotonPRO. We followed the standard operating procedure recommended by the manufacturer, and that performed in previous studies using the device. The device has been shown to have good reliability in a variety of populations, e.g., [7,16]. Nonetheless, our results should be viewed in accordance with the limitations. Firstly, our sample consisted of a relatively homogeneous small cross-sectional sample of White British patients with mild to moderate kidney function. Secondly, there are different known (and unknown) variables that might influence muscle tone, stiffness, and elasticity, such as age, body temperature, subcutaneous soft tissue, and the degree of physical activity prior to examination. Whilst we tried to adjust for co-variants where possible, some of these variables were not collected and therefore could not be controlled for. These factors may go some way to explain the differences in values across studies. Further research is needed to explore the utility of the myotonometry method in CKD patients, the clinical value of the numbers observed, and investigate how sarcopenia, obesity, and device location (e.g., different muscles) may alter results. Our findings indicate that larger studies are needed using the MyotonPRO to provide reference data in both males and females of different ages and disease stages, to enable comparison with patients in rehabilitation and for monitoring changes with treatment [7].

4. Materials and Methods

4.1. Study Design

The present analysis consists of sub-study data taken from the multi-centre observational cross-sectional DIMENSION-KD study (ISRCTN84422148). Participants attended a single visit to Leicester General Hospital, Leicester, UK, for a range of physiological assessment measures, which included body composition and physical function testing. Participants were recruited from general nephrology outpatient clinics and GP practices between July 2018 and February 2020. Participants were included if they had been: (1) diagnosed with a kidney condition (CKD 1–5 not requiring dialysis) in accordance with NICE guidance, (2) were aged 18 years or older, and (3) were able to provide informed consent. Participants undergoing dialysis treatment as a form of renal replacement therapy were excluded. The study was granted national research ethical approval by the Leicester Research Ethics Committee (18/EM/0117). All patients provided informed written consent and the study was conducted in accordance with the Declaration of Helsinki.

4.2. Demographic and Health Variables

Demographic (age, sex, ethnicity) and health-related variables (co-morbidities, BMI) were self-reported via a questionnaire. Upon receipt of the completed survey, participant’s clinical data, including renal function, cause of disease (if known), Hb, and albumin were extracted from the patient’s medical records. Co-morbidities were cross-referenced where possible to those self-reported on the survey.

4.3. Muscle Myotonometry

Muscle properties were assessed using a myotonometer, the MyotonPRO (Myoton AS, Tallinn, Estonia). Measurements were taken on the rectus femoris muscle of the upper leg; specifically, each measurement was taken perpendicular to the longitudinal axis of the quadriceps femoris at the midpoint between the greater trochanter and the proximal end of the patella. The rectus femoris is essential in lower body function, gait, and balance [3,35]. During the scan, patients were sat upright with hip flexion of ~120° and legs flat out in front. The probe (or testing end) of the device was placed perpendicular to the skin surface directly above the area to be measured. As per previous research, a brief mechanical impulse lasting 15 microseconds was applied to the muscle at a force of 0.40 newtons [20,25]. A total of 10 impulses (with a 1 s interval between each impulse) were applied consecutively. Two sets of 10 impulses were made. The coefficient of variation (CV) of the 10 measurements was displayed and any set of parameters with a CV > 3% was discarded and the test was repeated. The tests were performed by two researchers (due to the high reliability of the device, no inter-rater reliability data were collected).

The resulting damped oscillations of the muscle were recorded by an accelerometer, and numerical values were calculated to show the muscle’s biomechanical and viscoelastic properties. The MyotonPRO measures three central muscle properties:

-

oscillation frequency (in hertz, Hz), which is the intrinsic tension (or tone) of the muscle in its passive state

-

dynamic stiffness (in newtons per metre), the resistance to deformation

-

logarithmic decrement, the elasticity of the muscle [36]

Measurements were taken in both the right and left legs. Reliability between repeated tests was assessed by paired-sample t-tests and intraclass correlation coefficient (two-way mixed single measures); between 0.750 and 0.900 was defined as ‘good’; above 0.900 was defined as ‘excellent’ [37]. Previous research has shown good to excellent reliability (between repetitions, days, researchers) for the device in both younger and older adults [7,20,25]. Due to the negligible differences between sides and test number (Supplementary Material S1), data from the first test conducted on the right side were used for all analyses.

4.4. Physical Performance and Muscle Function

Muscle function and physical performance were assessed using frequently used and recommended assessments of the lower limb [38]. The sit-to-stand-60 (STS-60) test was employed as a measure of lower body strength and muscle endurance. For this test, the patient sat on a seat (17 in. [43.2 cm] from the ground) with their feet slightly apart. With their hands across their chest, patients were asked to perform as many STS cycles as possible in 60 s. Similarly, the STS-5 test recorded how long it took each participant to perform 5 repetitions. Usual gait speed was measured over a marked 4 m course, with the faster of two trials used for analysis. Along with three measures of standing balance, both the STS-5 and gait speed formed part of the ‘Short Physical Performance Battery’ (SPPB).

Validated in CKD patients [39], the incremental shuttle walk test (ISWT) was used as a measure of exercise capacity and cardiorespiratory fitness. For this test, the patient was required to walk between two cones 10 m apart. Patients maintained a speed regulated by an external auditory beep. The walking speed was initially very slow (0.5 m/s), but for every minute stage, the required walking speed increased by 0.2 m/s. The patient maintained cadence with the beeps until volitional exhaustion or until they could no longer keep up with the required pace. The total number of shuttles and distance walked (m) was calculated. Postural sway (both displacement area in mm² and velocity in mm/s) was measured using a Fysiometer device (FysioMeter ApS, Brønderslev, Denmark) as previously described [40].

4.5. Statistical Analysis

Data are presented as mean and standard deviation (SD) unless otherwise stated. Data analysis was performed on SPSS V26 (IBM, Armonk, NY, USA). General linear regression models were used to explore the association between muscle properties and tests of physical function and postural stability. Due to multi-collinearity, individual muscle properties (tone, stiffness, elasticity) were entered independently as independent variables. Adjusted models were conducted using age, sex, eGFR, and muscle (rectus femoris) cross-sectional area (CSA) assessed using ultrasonography (previously described [3,41]) as co-variants. Ethnicity was not included as a co-variant due to the homogenous nature of the sample (predominantly White). Asymmetries between right and left sides were calculated as a % of the mean value. Basic demographic and clinical characteristics (age and sex, and eGFR, Hb, albumin, and BMI) were investigated as possible predictive variables of muscle properties and were assessed using a multi-variate general linear regression model. Data are shown as standardised beta, t-value, and p-value. Statistical significance was accepted as p < 0.050.

5. Conclusions

Using a novel handheld myotonometer, the MyotonPRO, this study found that CKD patients exhibit a reduction in muscle tone, stiffness, and elasticity. These viscoelastic muscle properties showed no consistent associations with physical performance. Such an absence of effect does not mean that these properties are not important, and it is likely that passive muscle properties in the relaxed state do not represent functional evaluation during the contracted dynamic state. Further work is needed to identify appropriate meaningful reference data for comparison and to explore the mechanisms that may be responsible for these abnormal findings in CKD patients.