Screening for muscle wasting and dysfunction in patients with chronic kidney disease

Carrero, Juan Jesús; Johansen, Kirsten L.; Lindholm, Bengt; Stenvinkel, Peter; Cuppari, Lílian; Avesani, Carla María

doi:10.1016/j.kint.2016.02.025

Cited by 219 publications

(201 citation statements)

References 119 publications

(156 reference statements)

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“…The aetiology of uremic myopathy is multifactorial ( Table 2), including physical inactivity, reduced protein intake, vitamin D deficiency, hyperparathyroidism, metabolic acidosis, electrolyte disorder, low serum levels of testosterone, resistance to growth hormone and insulin, accumulation of uremic toxins, and carnitine deficiency, which can lead to mitochondrial dysfunction 105, 106. Observational studies have shown an inverse correlation between muscle mass and blood levels of IL‐6 and C reactive protein in CKD patients,12, 107, 108 postulating inflammation as an additional cause of muscle wasting in this population 109, 110, 111.…”

Section: Bone and Musculoskeletal Abnormalities In Chronic Kidney Dismentioning

confidence: 99%

“…Although the process by which inflammation produces sarcopenia has not yet been identified, several mechanisms have been described, including activation of NF‐κβ and angiotensin II pathways,112, 113, 114 and the ATP‐dependent ubiquitin–proteasome system, which has been identified as the most important pathway for muscle wasting 115. Excellent reviews on muscle wasting and dysfunction in patients with CKD have been recently published 102, 106…”

Section: Bone and Musculoskeletal Abnormalities In Chronic Kidney Dismentioning

confidence: 99%

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Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

Molina

Carrero

Bover

et al. 2017

J cachexia sarcopenia muscle

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The spectrum of activity of vitamin D goes beyond calcium and bone homeostasis, and growing evidence suggests that vitamin D contributes to maintain musculoskeletal health in healthy subjects as well as in patients with chronic kidney disease (CKD), who display the combination of bone metabolism disorder, muscle wasting, and weakness. Here, we review how vitamin D represents a pathway in which bone and muscle may interact. In vitro studies have confirmed that the vitamin D receptor is present on muscle, describing the mechanisms whereby vitamin D directly affects skeletal muscle. These include genomic and non‐genomic (rapid) effects, regulating cellular differentiation and proliferation. Observational studies have shown that circulating 25‐hydroxyvitamin D levels correlate with the clinical symptoms and muscle morphological changes observed in CKD patients. Vitamin D deficiency has been linked to low bone formation rate and bone mineral density, with an increased risk of skeletal fractures. The impact of low vitamin D status on skeletal muscle may also affect muscle metabolic pathways, including its sensitivity to insulin. Although some interventional studies have shown that vitamin D may improve physical performance and protect against the development of histological and radiological signs of hyperparathyroidism, evidence is still insufficient to draw definitive conclusions.

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Section: Bone and Musculoskeletal Abnormalities In Chronic Kidney Dismentioning

confidence: 99%

Section: Bone and Musculoskeletal Abnormalities In Chronic Kidney Dismentioning

confidence: 99%

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

Molina

Carrero

Bover

et al. 2017

J cachexia sarcopenia muscle

Self Cite

View full text Add to dashboard Cite

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“…Various normalization metrics, reference populations (e.g., young healthy individuals versus age-matched controls), and instruments to estimate muscle quantity (e.g., bioelectrical impedance analysis, BIA; dual x-ray absorptiometry, DXA) have been applied by investigators around the world. 11 Although height-squared is commonly employed as an indexing metric of muscle mass, 2, 3, 12 overweight or obese individuals with low muscle mass relative to their size may not be classified as sarcopenic by this method, 13, 14 and low muscle mass based on criteria that adjust for both height and weight may be more strongly associated with weakness and poor physical performance than low muscle mass based on methods using either height or weight alone. 15 Therefore, some experts have recommended indexing muscle mass to height- and weight-adjusted metrics of body size (e.g., body mass index [BMI], body surface area [BSA]).…”

Section: Introductionmentioning

confidence: 99%

Sarcopenia and its individual criteria are associated, in part, with mortality among patients on hemodialysis

Kittiskulnam

Chertow

Carrero

et al. 2017

Kidney International

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The relative importance of sarcopenia and its individual components as independent predictors of mortality in the dialysis population have not been determined. We estimated whole-body muscle mass using pre-dialysis bioimpedance spectroscopy measurements in 645 ACTIVE/ADIPOSE enrolled prevalent hemodialysis patients from San Francisco and Atlanta. Low muscle mass was defined as two standard deviations below sex-specific means for young adults from NHANES and indexed to height2, body weight, body surface area, or body mass index. We evaluated the association of sarcopenia (low muscle mass) by four indexing methods, weak handgrip strength, and slow gait speed with mortality. Seventy-eight deaths were observed during a mean follow-up of 1.9 years. Sarcopenia was not significantly associated with mortality after adjusting for covariates. No muscle mass criteria were associated with death, regardless of indexing metrics. In contrast, having weak grip strength or slow walking speed was associated with mortality in the adjusted model. Only gait slowness significantly improved the predictive accuracy for death with an increase in C-statistic from 0.63 to 0.68. However, both gait slowness and hand grip weakness significantly improved the net reclassification index compared to models without performance measures (50.5% for slowness and 33.7% for weakness), whereas models with muscle size did not. Neither sarcopenia nor low muscle mass by itself was a better predictor of mortality than functional limitation alone in patients receiving hemodialysis. Thus, physical performance measures, including slow gait speed and weak hand grip strength, were associated with mortality even after adjustment for muscle size and other confounders.

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“…Because this approach greatly reduces the time burden and discomfort for the patient, 11 C-MET imaging with PET/CT may be useful to characterize skeletal muscle deficits in this population. By the same token, it will also be applicable to investigate skeletal muscle function in other disease groups, such as chronic kidney disease [29–31], HIV [32, 33] or diabetic patients [34–36]. Moreover, because the PET image is co-registered with a CT image, it is possible to correlate the K i measure with measures of muscle cross-sectional area and lean tissue Hounsfield Unit, a measure of fatty infiltration which is associated with altered muscle strength and physical function.…”

Section: Discussionmentioning

confidence: 99%

11C-L-methyl methionine dynamic PET/CT of skeletal muscle: response to protein supplementation compared to L-[ring 13C6] phenylalanine infusion with serial muscle biopsy

et al. 2017

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ObjectiveThe objective of this study was to determine if clinical dynamic PET/CT imaging with 11C-L-methyl-methionine (11C-MET) in healthy older women can provide an estimate of tissue-level post-absorptive and post-prandial skeletal muscle protein synthesis that is consistent with the more traditional method of calculating fractional synthesis rate (FSR) of muscle protein synthesis from skeletal muscle biopsies obtained during an infusion of L-[ring 13C6] phenylalanine (13C6-Phe).MethodsHealthy older women (73 ± 5 years) completed both dynamic PET/CT imaging with 11C-MET and a stable isotope infusion of 13C6-Phe with biopsies to measure the skeletal muscle protein synthetic response to 25 g of a whey protein supplement. Graphical estimation of the Patlak coefficient Ki from analysis of the dynamic PET/CT images was employed as a measure of incorporation of 11 C-MET in the mid-thigh muscle bundle.ResultsPost-prandial values [mean ± standard error of the mean (SEM)] were higher than post-absorptive values for both Ki (0.0095 ± 0.001 vs. 0.00785 ± 0.001 min−1, p < 0.05) and FSR (0.083 ± 0.008 vs. 0.049 ± 0.006%/h, p < 0.001) in response to the whey protein supplement. The percent increase in Ki and FSR in response to the whey protein supplement was significantly correlated (r = 0.79, p = 0.015).ConclusionsDynamic PET/CT imaging with 11C-MET provides an estimate of the post-prandial anabolic response that is consistent with a traditional, invasive stable isotope, and muscle biopsy approach. These results support the potential future use of 11C-MET imaging as a non-invasive method for assessing conditions affecting skeletal muscle protein synthesis.

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Screening for muscle wasting and dysfunction in patients with chronic kidney disease

Cited by 219 publications

References 119 publications

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

Vitamin D, a modulator of musculoskeletal health in chronic kidney disease

Sarcopenia and its individual criteria are associated, in part, with mortality among patients on hemodialysis

11C-L-methyl methionine dynamic PET/CT of skeletal muscle: response to protein supplementation compared to L-[ring 13C6] phenylalanine infusion with serial muscle biopsy

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