Quality over quantity? Association of skeletal muscle myosteatosis and myofibrosis on physical function in chronic kidney disease

Wilkinson, Thomas J.; Gould, Douglas W.; Nixon, Daniel; Watson, Emma; Smith, Alice C.

doi:10.1093/ndt/gfy139

Cited by 62 publications

(70 citation statements)

References 51 publications

(119 reference statements)

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“…Rectus femoris anatomical cross-sectional area (CSA) was determined using B-mode 2-D ultrasonography (Hitachi EUB-6500; probe frequency 7.5 MHz) as previously described 32,41,42 and has recently been validated against MRI 43 . Images were captured at the mid-point between the greater trochanter and the superior aspect of the patella on the midsagittal plane of the thigh.…”

Section: Quadriceps Muscle Sizementioning

confidence: 99%

Reductions in skeletal muscle mitochondrial mass are not restored following exercise training in patients with chronic kidney disease

et al. 2019

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Patients with chronic kidney disease (CKD) exhibit reduced exercise capacity, poor physical function and symptoms of fatigue. The mechanisms that contribute to this are not clearly defined but may involve reductions in mitochondrial function, mass and biogenesis. Here we report on the effect of non-dialysis dependent CKD (NDD-CKD) on mitochondrial mass and basal expression of transcription factors involved in mitochondrial biogenesis compared to a healthy control cohort (HC). In addition, we sought to investigate the effect of a 12-week exercise-training programme on these aspects of mitochondrial dysfunction in a NDD-CKD cohort.For the comparison between NDD-CKD and HC populations, skeletal muscle biopsies were collected from the vastus lateralis (VL) of n=16 non-dialysis dependent CKD patient's stage 3b-5 (NDD-CKD) and n=16 healthy controls matched for age, gender and physical activity (HC). To investigate the effect of exercise training, VL biopsies were collected from n=17 NDD-CKD patients before and after a 12-week exercise intervention that was comprised of aerobic exercise (AE) or a combination of aerobic exercise and resistance training (CE). Mitochondrial mass was analysed by citrate synthase activity and mitochondrial protein content by Porin expression, whilst the expression of transcription factors involved in mitochondrial biogenesis were quantified by real-time qPCR. NDD-CKD patients exhibited a significant reduction in mitochondrial mass when compared to HC, coupled to a reduction in PGC-1α, NRF-1, Nrf2, TFam, mfn2 and SOD1/2 gene expression. 12-weeks of exercise training resulted in a significant increase in PGC-1α expression in both groups, with no further changes seen across indicators of mitochondrial biogenesis. No significant changes in mitochondrial mass were observed in response to either exercise programme. NDD-CKD patients exhibit reduced skeletal muscle mitochondrial mass and gene expression of 1756 |

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Section: Quadriceps Muscle Sizementioning

confidence: 99%

Reductions in skeletal muscle mitochondrial mass are not restored following exercise training in patients with chronic kidney disease

et al. 2019

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“…Importantly, quadriceps muscle size and function is well recognized as an important contributor to reduce exercise capacity and increase morbidity and mortality in chronic disease populations . Indeed, we have recently shown that RF‐CSA measured by ultrasound is independently associated with physical performance measures amongst non‐dialysis CKD patients . Therefore, being able to quickly and accurately quantify changes in lower limb muscle that are functionally important—such as RF—is of particular interest to clinicians and researchers.…”

Section: Discussionmentioning

confidence: 99%

“…9,23 Indeed, we have recently shown that RF-CSA measured by ultrasound is independently associated with physical performance measures amongst non-dialysis CKD patients. 21 Therefore, being able to quickly and accurately quantify changes in lower limb muscle that are functionally important-such as RF-is of particular interest to clinicians and researchers.…”

Section: Discussionmentioning

confidence: 99%

“…In CKD populations, ultrasound has recently been used to identify the presence of low muscle mass, measured as quadriceps thickness, in end stage renal disease patients receiving haemodialysis . We have shown that ultrasound‐derived RF‐CSA is associated with physical performance amongst patients with CKD stages 3b–5 not requiring dialysis . The utility of ultrasound to detect changes in muscle mass in response to an intervention in CKD populations, in comparison with a gold standard (i.e.…”

Section: Introductionmentioning

confidence: 96%

“…20 We have shown that ultrasound-derived RF-CSA is associated with physical performance amongst patients with CKD stages 3b-5 not requiring dialysis. 21 The utility of ultrasound to detect changes in muscle mass in response to an intervention in CKD populations, in comparison with a gold standard (i.e. MRI), is unknown.…”

Section: Introductionmentioning

confidence: 99%

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Ultrasound assessment of muscle mass in response to exercise training in chronic kidney disease: a comparison with MRI

Gould

Watson

Wilkinson

et al. 2019

J cachexia sarcopenia muscle

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Background Chronic kidney disease (CKD) is a catabolic condition associated with muscle wasting and dysfunction, which associates with morbidity and mortality. There is a need for simple techniques capable of monitoring changes in muscle size with disease progression and in response to interventions aiming to increase muscle mass and function. Ultrasound is one such technique; however, it is unknown how well changes in muscle cross‐sectional area (CSA) measured using ultrasound relate to changes in whole muscle volume measured using magnetic resonance imaging. We tested whether rectus femoris CSA (RF‐CSA) could be used as a valid indication of changes in quadriceps muscle volume as a single measure of muscle size and following a 12 week exercise intervention that resulted in muscle hypertrophy. Methods Secondary analysis of data was collected from the ExTra CKD study (ISRCTN 36489137). Quadriceps muscle size was assessed from 36 patients with non‐dialysis CKD before and after 12 weeks of supervised exercise that resulted in muscle hypertrophy. Results Strong positive correlations were observed between RF‐CSA and quadriceps volume at baseline ( r 2 = 0.815, CI 0.661 to 0.903; P < 0.001) and following 12 week exercise ( r 2 = 0.845, CI 0.700 to 0.923; P < 0.001). A moderate positive association was also observed between changes in RF‐CSA and quadriceps following exercise training (rho = 0.441, CI 0.085 to 0.697; P = 0.015). Bland–Altman analysis revealed a small bias (bias 0.6% ± 12.5) between the mean percentage changes in RF‐CSA and quadriceps volume but wide limits of agreement from −24 to 25. Conclusions Rectus femoris CSA appears to be a reliable index of total quadriceps volume as a simple measure of muscle size, both as a single observation and in response to exercise training in non‐dialysis CKD patients.

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Myosteatosis as an independent risk factor for mortality after kidney allograft transplantation: a retrospective cohort study

Morel

Ouamri

Canouï‐Poitrine

et al. 2021

J cachexia sarcopenia muscle

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Background Patients with end-stage renal disease may display both a loss of skeletal muscle mass and an increase in muscle fat deposits. We aimed to analyse the impact of low skeletal muscle mass index (SMI, surrogate marker of sarcopenia) and low muscle density (MD, surrogate marker of myosteatosis) on patient survival after kidney transplantation (KT). Methods In a retrospective cohort of 200 kidney transplant recipients (KTr), we measured on an unenhanced cross-sectional computed tomography scan taken at the level of the third lumbar vertebra within the previous year or at the time of KT, both SMI (muscle cross-sectional area normalized for height 2 , reported in cm 2 /m 2 ) and MD (mean attenuation of muscle cross-sectional area, expressed in Hounsfield units). We determined age-specific and sex-specific normality thresholds on 130 healthy subjects. The baseline factors associated with low MD were assessed by logistic regression analysis. Cox proportional hazard univariable and multivariable models were constructed to identify predictive factors of patient survival. Results Among the 200 patients of the cohort, 123 were male (62%), and mean age was 54.8 ± 13.8 years. A total of 181 KTr required renal replacement therapy before KT (91%), and 36 KTr (18%) received repeat kidney transplant after previous failed KT. Mean MD was 30.6 ± 9 HU in men and 29.7 ± 8.3 HU in women, whereas SMI was 49.7 ± 8.6 cm 2 /m 2 in men and 42.3 ± 7.3 cm 2 /m 2 in women. MD was below the 2.5th percentile for the healthy population in 49 KTr (25%), defining the myosteatosis group, while SMI was below the 2.5th percentile for the reference population in 10 KTr (5%). Independent risk factors for myosteatosis were two or more KT [adjusted odds ratio (aOR) 5.2, 95% confidence interval (95% CI): 2.22-12.4, P = 0.0001], a history of stroke (aOR 3.7, 95% CI: 1.30-10.7, P = 0.015), and body mass index > 25 kg/m 2 (aOR 2.94, 95% CI: 1.4-6.18, P = 0.004). Myosteatosis was independently associated with mortality [adjusted hazard ratio (aHR) 2.12, 95% CI: 1.06-4.24, P = 0.033], as were cardiovascular disease (HR 2.06, 95% CI: 1.02-4.15, P = 0.043) and age (aHR 1.06, 95% CI: 1.03-1.09, P = 0.0003). Low SMI was not associated with mortality. Conclusions Myosteatosis, which was more prevalent than low skeletal muscle mass, might be an important prognostic marker in patients undergoing KT.

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Quality over quantity? Association of skeletal muscle myosteatosis and myofibrosis on physical function in chronic kidney disease

Cited by 62 publications

References 51 publications

Reductions in skeletal muscle mitochondrial mass are not restored following exercise training in patients with chronic kidney disease

Reductions in skeletal muscle mitochondrial mass are not restored following exercise training in patients with chronic kidney disease

Ultrasound assessment of muscle mass in response to exercise training in chronic kidney disease: a comparison with MRI

Myosteatosis as an independent risk factor for mortality after kidney allograft transplantation: a retrospective cohort study

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