Abstract
End-stage renal disease (ESRD) is a prevalent disease that results from kidney failure in the last stage of chronic kidney disease. This disease has many chronic and debilitating symptoms, including muscle wasting. Unfortunately, current methods to diagnose muscle wasting, in this patient population, are rather imprecise and/or expensive. To develop a better method, this study examined the use of sonography across four separate patients with ESRD in a typical clinical setting. Multiple muscle measurements were taken in the patients’ upper arm via sonography, which were compared to laboratory test results and skinfold measurements. This multiple case comparison demonstrates the feasibility of using sonography to measure subcutaneous tissue and muscle mass in this patient population. It also has the potential to correlate with or support other clinical measures of disease severity. Further study is recommended to examine these correlations and to identify clinical implications for sonographic measurement of overall muscle wasting.
According to the most recent reports from the US renal data system, more than 660,000 Americans are currently being treated for end-stage renal disease (ESRD). 1 ESRD, more commonly referred to as kidney failure, is the last stage of chronic kidney disease (CKD). 2 Approximately 70% of these patients are being treated with dialysis at around 6479 different facilities in the United States. 1 The most common cause of ESRD is diabetes, with a secondary cause being hypertension. Other chronic causes of renal failure include nephrotic syndromes, urinary tract problems, autoimmune diseases including lupus, and genetic diseases such as polycystic kidney disease. In some cases, there is acute renal injury caused by heart attack, drug abuse, or restriction of blood flow to the kidneys. 2 No matter how patients develop renal failure, this condition has a negative effect on the entire human body. Patients experience chronic symptoms such as headache, poor appetite, bone pain, malaise, muscle cramps, change in mental alertness, and sarcopenia or muscle wasting (MW). 3
MW is a common feature of patients with CKD, and it is estimated that up to 75% of these patients demonstrated evidence of sarcopenia. 4 MW can be defined as atrophy, weakening, or loss of muscle that is caused by either disease or lack of use. This loss in muscle decreases the patient’s strength and mobility. 5 This symptom predisposes this vulnerable patient population to increased risk of comorbid complications, frailty, poor quality of life, and premature death. Current assessment tools to diagnose and monitor MW are rather imprecise and/or expensive. 6 In an effort to improve assessment of MW in patients with CKD, this study evaluated the feasibility of portable sonography, within a clinical setting, to examine MW in a small sample of patients with ESRD.
Methods
The Ohio State University’s Office of Responsible Research Practices approved an institutional review board application. Four participants were recruited and consented during an outpatient appointment to the renal transplant clinic. During their clinical examination, anthropometric data and renal function laboratory values were obtained, and a nutritional status screening was conducted that included handgrip strength assessment, timed up-and-go test, and a nutrition-focused physical examination. Laboratory values for creatinine and blood urea nitrogen (BUN) level, along with record of any other comorbidities, were obtained from the patient’s chart. In addition to the standard clinical screening, a dynamic sonographic examination was completed on both upper arms. A set of sonographic images of the biceps and triceps muscles was recorded and analyzed from the arm with the least amount of surgical intervention. All clinical measures and sonographic imaging were completed by a registered dietitian (RD) with scanning assistance from a trained sonographer, as well as image analysis. Although extensive data were collected, this report is focused on describing the relationship of external anthropometric measures to internal sonographic measures of muscle size.
Anthropometric Measures
The RD began by taking a triceps skinfold thickness (SFT) measurement on the participant’s dominant arm. If the participant was being treated with dialysis, the arm without the dialysis access was used. The RD palpated the acromion and olecranon processes on the arm and measured the midpoint between the two using a tape measure. A mark was then made at the midpoint where skin calipers were used to measure triceps SFT to the closest millimeter. A midarm circumference (MAC) measurement was taken using the tape measure at the same location.
Imaging Protocol
All sonographic images were acquired using a GE Logic-i laptop (GE Healthcare, Chicago, IL, USA) with a 12-MHz linear transducer using a musculoskeletal preset. The transducer was placed on the mark over the triceps muscle in the transverse plane to acquire the first image. Staying at the level of the mark, the transducer was moved medially to the bicep muscle, where two images were then taken in the transverse and longitudinal planes. All structures were identified in the image, beginning at the surface with the skin to the humerus that was visualized in the far field of each image (Figure 1). Anterior-posterior measurements of the subcutaneous tissue, triceps, and biceps muscles were obtained and recorded. The thickness of the skin was measured on the triceps image to compare to the external SKT measurement. Each measurement was completed three times and the average was recorded.
A longitudinal sonographic image over the biceps muscle area. This patient was suspected to have sarcoidosis, and the image demonstrates each tissue layer that can be measured.
Results
Four participants with ESRD were recruited through an outpatient renal transplant clinic. All participants were male, three were Caucasian, and one was African American. The average age was 54 years, and the mean (SD) body mass index (BMI) was 31.66 (6.21) kg/m2. Individual participant clinical data are summarized in Table 1, and averaged summary data across participants are provided in Table 2. A description of findings for each of the four cases follows.
Descriptive, Clinical, Anthropometric, and Sonographic Data for Each of the Four Participants.
Abbreviations: BMI, body mass index; BUN, blood urea nitrogen.
Measures obtained using sonography.
Mean ± SD and Range of Measurements for Descriptive, Anthropometric, and Sonographic Variables Across All Participants (n = 4).
Abbreviations: BMI, body mass index; BUN, blood urea nitrogen.
Measures obtained using sonography.
Case 1
Participant 1 was a 60-year-old African American man with CKD caused by hypertensive nephrosclerosis. He had a BMI of 40.72 kg/m2, a weight of 124.2 kg, BUN of 51 mg/dL, and creatinine measuring 9.04 mg/dL. At the time of the examination, participant 1 was actively undergoing hemodialysis. A series of other comorbidities were also noted, such as ischemic heart disease, secondary hyperparathyroidism, mild chronic obstructive pulmonary disease, hypertension, heart failure prior to the initiation of hemodialysis, and anemia. When measured with calipers, the triceps SFT measurement was 22 mm, and when measured with sonography, the skin thickness at this point measured 2 mm. The MAC of participant 1 was 39 cm. The arm thickness of the subcutaneous tissue and triceps was 5.2 cm, and the subcutaneous tissue and biceps thickness was 4.0 cm and 4.4 cm in the longitudinal and transverse images, respectively.
Case 2
Participant 2 was a 68-year-old Caucasian man with CKD caused by autosomal dominant polycystic kidney disease. He had a BMI of 26.64 kg/m2, a weight of 80.6 kg, a BUN of 33 mg/dL, and creatinine of 7.46 mg/dL. This participant was currently undergoing hemodialysis and had hypertension and chronic obstructive pulmonary disease. His triceps SFT was 9 mm, with a sonographic skin thickness of 1 mm and a MAC of 30 cm. The transverse image of the subcutaneous tissue and triceps measured 3.7cm. The sonogram showed that the subcutaneous tissue and biceps in the longitudinal image measured 3.2 cm, while the transverse image of the same area measured 2.7 cm.
Case 3
Participant 3 was a 47-year-old Caucasian man with a CKD diagnosis caused by nephrotic syndrome. This participant had a BMI of 30 kg/m2, weight of 100.45 kg, a BUN of 40 mg/dL, and creatinine measuring 3.13 mg/dL. Unlike the other participants, he was not currently undergoing any form of renal dialysis but did have a significant number of comorbidities, including hypertension, previous cardiac arrest, ventricular fibrillation, and hyperlipidemia. When measured with calipers, the triceps SFT measurement of participant 3 was 14 mm, with a sonographic skin thickness measure of 1 mm. The MAC of participant 3 measured 35 cm. The transverse image of the subcutaneous tissue and triceps measured 4.2 cm, and the sonogram showed that the subcutaneous tissue and biceps muscle in the longitudinal image measured 3.9 cm, while the transverse image of the same area measured 3.7 cm.
Case 4
Participant 4 was a 41-year-old Caucasian man with CKD secondary to polycystic kidney disease. He had a BMI of 29.27 kg/m2, weight of 84.8 kg, a BUN of 71 mg/dL, and creatinine measuring 4.4 mg/dL. This participant was being treated with hemodialysis and had multiple surgical histories of bilateral native nephrectomy occurring within recent years. However, there were no other significant comorbidities noted in the medical record for this participant. When measured with calipers, the triceps SFT measurement was 11 mm, the skin thickness over the triceps was 1 mm, and the MAC was 33 cm. Participant 4 had a subcutaneous tissue and triceps muscle thickness of 4.4 cm and the subcutaneous tissue and biceps thickness of 4.0 cm in both transverse and longitudinal images.
Discussion
As previously discussed, in patients with CKD, the risk of morbidity and mortality is increased with the loss of overall muscle mass. Muscle wasting is caused by catabolic pathways that include the activation of caspase-3, lysosomes, ubiquitin-proteasome system, and myostatin, which is a negative regulator of skeletal muscle growth. Complications associated with CKD, such as inflammation, increased angiotensin II levels, metabolic acidosis, defective insulin signaling, abnormal appetite regulation, and impaired microRNA responses, can initiate these pathways. Unfortunately, methods used for detecting muscle atrophy are cumbersome; therefore, muscle loss often goes unrecognized until there is visible wasting or weight loss. 7 Current imaging methods to detect overall muscle mass such as magnetic resonance imaging, computed tomography (CT), and dual-energy X-ray absorptiometry (DXA) have a high precision and accuracy. However, these imaging modalities are expensive, and CT and DXA use ionizing radiation. 8 Moreover, for patients with CKD, DXA cannot distinguish between extracellular fluid and lean muscle, adding much more difficulty to this imaging assessment. 9
This study examined the feasibility of using sonography as the modality of choice to measure and assess overall subcutaneous tissue and muscle thickness. Sonography offers a cost-effective, noninvasive, and mobile imaging option that can be conveniently completed in an outpatient setting. This removes the inconvenience of having to refer the patient elsewhere. In this study, a portable ultrasound machine the size of a computer laptop was used, which made it possible to set up directly on the counter or in a chair next to the patient. This type of machine was convenient to move and match the participants’ mobility needs and clinical examination space limitations. This study demonstrates that it is feasible to obtain objective thickness measures of the arm in patients with ESRD rather than subjectively assessing possible muscle wasting in this patient population.
Sonography has been shown to be a reliable measure of muscle thickness in the anterior and posterior upper arm. 10 In a previous prospective blinded study, muscle thickness measurements using sonography were investigated for reliability using a test-retest method in patients hospitalized with acute stroke. Two different cohorts were examined by one sonographer with a variety of different anatomical sites being measured. The study conducted found that, along with a few others, the anterior and posterior upper arm measurement sites were within acceptable ranges (intraclass correlation coefficients, 0.60–1.00; mean percent difference range, 0%–5%; and method error range, 0–5 mm) and were considered reliable to use for measures of muscle thickness in this patient population. 10 In the current study, clinical researchers used this information to examine patients with CKD.
In another study, consisting of 50 different patients with multiple-organ failure, sonography was used to identify muscle wasting in the presence of edema. Measurements of both the MAC and muscle thickness using sonography were made at 1- to 3-day intervals. They found that sonography was able to identify muscle wasting in critically ill patients with severe fluid retention for most patients (48/50). 11 In the current study, the participants who were evaluated did not have the complication of severe edema. When analyzing and collecting measurements from the sonogram, taken in the anterior and posterior upper arm, the sonographer measured from the surface of the skin to the bone to better relate to what is done clinically when evaluating for upper arm thickness during nutritional assessments (Figures 2 and 3).
Sample measurement of the depth of the posterior arm at the triceps muscle area, in the transverse plane, for a patient suspected of having sarcoidosis.
Longitudinal sonographic image of the triceps muscle of a patient with a suspected diagnosis of sarcoidosis.
Current reference standards for skin, subcutaneous tissue, and muscle measurements completed with sonography do not exist. Measurements in this study were recorded and compared to those taken by the RD using skin calipers or tape measures. Human error may influence the results obtained by these tools. A standardized protocol exists to complete SFT, but errors such as marking the incorrect site on the participant or holding the calipers and skinfold at the incorrect angle may influence measurements. Practitioners also need sufficient practice to recognize the varied tissue layers and thereby improve measurement accuracy.
Conclusions
Results of this multiple case report demonstrated that it is feasible to objectively measure arm thickness in patients with CKD and ESRD and that external SFT measurements by calipers and internal skin thickness measurements using sonography provide different types of information. This highlights an opportunity for advancement in the assessment of ESRD through partnership among sonographers and other health care providers. The addition of repeated sonographic assessment across time as part of a renal transplant evaluation could add a noninvasive way to objectively monitor changes in underlying muscle mass over time. Moreover, because measures would be compared within the individual patient, this method could minimize potential diagnostic error that results from the use of healthy adult reference data. Future studies should be performed to further examine muscle wasting in this patient population, specifically to determine how these measures change across time and are related to other aspects of the clinical evaluation.
Footnotes
Acknowledgements
The team thanks the OSU Renal Division, and especially Krista Matthews, MBA, RDN, LD, for allowing us to conduct a proof of concept within their clinical service.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
