Sarcopenia In Chronic Kidney Disease Research Articles

#2439 The association between vitamin D deficiency and sarcopenia in patients with pre-dialysis CKD

Abstract Background and Aims Sarcopenia is characterized by a progressive and widespread loss of skeletal muscle, leading to muscle weakness and frailty. While primary sarcopenia is linked to aging, secondary sarcopenia can independently occur, especially in chronic conditions like chronic kidney disease (CKD). Investigating sarcopenia in CKD patients has become a focal point in research due to its significant impact on the quality of life, morbidity, and mortality of these individuals. Despite reports connecting vitamin D deficiency, prevalent in CKD, to sarcopenia in the general population, there is limited information regarding the specific relationship between vitamin D and sarcopenia in CKD. This study aims to explore the association between vitamin D deficiency and sarcopenia in patients with pre-dialysis CKD. Method This cross-sectional study enrolled 569 patients with pre-dialysis chronic kidney disease (CKD), defined as having an estimated glomerular filtration rate (eGFR) less than 60 ml/min/m2. Sarcopenia was assessed using computed tomography (CT)-derived skeletal muscle index (SMI), calculated based on the cross-sectional area of skeletal muscles at the 3rd lumbar vertebra. Using Korean-specific SMI cutoffs, patients were categorized into sarcopenic and non-sarcopenic groups. Logistic regression analyses were employed to explore associations between sarcopenia and baseline variables, including active vitamin D, specifically 1,25-dihydroxyvitamin D [1,25(OH)2D] level. Results Among the 569 patients, 278 had CKD stage 3, 198 had CKD stage 4, and 93 had CKD stage 5. The prevalence of sarcopenia increased with advancing CKD stage (CKD stage 3 vs. stage 4 vs. stage 5: 20.1% vs. 31.3% vs. 41.9%, P < 0.001). Univariate logistic regression analysis revealed an association between 1,25(OH)2D levels and sarcopenia. Additionally, age, male sex, diabetes, body mass index, eGFR, urinary albumin excretion levels, and serum levels of albumin, high-sensitive C-reactive protein (hsCRP), and intact parathyroid hormone were associated with sarcopenia. In multivariable logistic regression analysis, 1,25(OH)2D levels remained independently associated with sarcopenia (per 1 pg/dl increase, odds ratio [OR]: 0.84; 95% confidence interval [CI]: 0.80–0.87, P < 0.001). Age (per 1 year increase, OR: 1.04, 95% CI: 1.02–1.07, P < 0.001), diabetes (vs. non-diabetes, OR: 2.33, 95% CI: 1.39–3.89, P = 0.001), serum albumin (per 1 mg/dl increase, OR: 0.39, 95% CI: 0.22–0.71, P = 0.0023), and hsCRP (per 1 mg/dl increase, OR: 1.91, 95% CI: 1.25–2.92, P = 0.003) were also independently associated with sarcopenia. Conclusion This study revealed an independent association between 1,25(OH)2D levels and sarcopenia derived from CT scans in pre-dialysis CKD patients. This association retained significance even after adjusting for traditional risk factors for sarcopenia, such as age, diabetes, serum albumin, and hsCRP. Further prospective studies are necessary to determine whether therapy with exogenous 1,25(OH)2D drugs can improve sarcopenia in these patients.

Association of endothelial dysfunction and peripheral arterial disease with sarcopenia in chronic kidney disease.

Endothelial dysfunction and peripheral arterial disease (PAD), which disturb skeletal muscle microperfusion, are highly prevalent in patients with chronic kidney disease (CKD). We evaluated the association of endothelial dysfunction and PAD with sarcopenia in patients with non-dialysis CKD. This cross-sectional study included 420 patients with stages 3-5 non-dialysis CKD aged 69.0±11.8years. Skeletal muscle index (skeletal muscle mass/height2), handgrip strength, 6-m gait speed and strength of hip flexion and knee extension were measured. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019. Endothelial dysfunction and PAD were assessed using the vascular reactivity index (VRI) and ankle-brachial index (ABI), respectively. A VRI<1.0 was classified as poor endothelial function, and an ABI<0.9 was defined as PAD. Additionally, endothelial and inflammatory biomarkers, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), asymmetric dimethylarginine, endothelin-1 (ET-1) and interleukin-6, were measured in a subgroup of 262 patients. Among the participants, 103 (24.5%) were classified as having sarcopenia. Compared with patients without sarcopenia, those with sarcopenia had significantly lower ABI (1.04±0.16 vs. 1.08±0.15, P=0.028 for the right ABI; 1.01±0.16 vs. 1.06±0.16, P=0.002 for the left ABI) and VRI (0.83±0.57 vs. 1.08±0.56, P<0.001) and had higher serum levels of ICAM-1 (P<0.001), VCAM-1 (P=0.003) and ET-1 (P=0.037). Multivariate logistic regression revealed that, beyond age and body mass index, the average ABI (odds ratio [OR]: 0.81/0.1 increase; 95% confidence interval [CI]: 0.67-0.98; P=0.032) and VRI (OR: 0.93/0.1 increase; 95% CI: 0.88-0.98; P=0.010) were independently associated with sarcopenia. Among the endothelial biomarkers measured, ICAM-1 (OR: 2.47/1-SD increase; 95% CI: 1.62-3.75) and VCAM-1 (OR: 1.91/1-SD increase; 95% CI: 1.27-2.87) were independent predictors of sarcopenia. Group stratification based on the cut-offs of VRI and ABI showed that those with both poor VRI and ABI had the greatest risk for sarcopenia (OR: 4.22; 95% CI: 1.69-10.49), compared with those with normal VRI and ABI. Endothelial dysfunction and PAD are independently associated with sarcopenia in patients with stages 3-5 CKD, suggesting the dominant role of vascular dysfunction in sarcopenia.

Pharmacologic therapeutics in sarcopenia with chronic kidney disease.

Inflammation, metabolic acidosis, renin-angiotensin system activation, insulin resistance, and impaired perfusion to skeletal muscles, among others, are possible causes of uremic sarcopenia. These conditions induce the activation of the nuclear factor-kappa B and mitogen-activated protein kinase pathways, adenosine triphosphate ubiquitin-proteasome system, and reactive oxygen species system, resulting in protein catabolism. Strategies for the prevention and treatment of sarcopenia in chronic kidney disease (CKD) are aerobic and resistance exercises along with nutritional interventions. Anabolic hormones have shown beneficial effects. Megestrol acetate increased weight, protein catabolic rate, and albumin concentration, and it increased intracellular water component and muscle mass. Vitamin D supplementation showed improvement in physical function, muscle strength, and muscle mass. Correction of metabolic acidosis showed an increase in protein intake, serum albumin levels, body weight, and mid-arm circumference. The kidney- gut-muscle axis indicates that dysbiosis and changes in gut-derived uremic toxins and short-chain fatty acids affect muscle mass, composition, strength, and functional capacity. Biotic supplements, AST-120 administration, hemodiafiltration, and preservation of residual renal function are alleged to reduce uremic toxins, including indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Synbiotics reversed the microbiota change in CKD patients and decreased uremic toxins. AST-120 administration changed the overall gut microbiota composition in CKD. AST-120 prevented IS and PCS tissue accumulation, ameliorated muscle atrophy, improved exercise capacity and mitochondrial biogenesis, restored epithelial tight junction proteins, and reduced plasma endotoxin levels and markers of oxidative stress and inflammation. In a human study, the addition of AST-120 to standard treatment had modest beneficial effects on gait speed change and quality of life.

Muscle ultrasound to diagnose sarcopenia in chronic kidney disease: a systematic review and bayesian bivariate meta-analysis

ObjectiveThe aim of this systematic review was to assess the diagnostic test accuracy of muscle ultrasound for sarcopenia among chronic kidney disease (CKD) populations.BackgroundSarcopenia has become a worldwide health issue, especially for CKD patients. Conventional techniques of muscle mass assessment often prove limited, thus prompts increasing interest in ultrasound suitability.MethodsWe searched the Cochrane Library, PubMed and Embase for literature published up to June 2023. Ultrasound diagnosis of sarcopenia in CKD patients was included. Two independent investigators used the Quality Assessment Tool for Diagnosis Accuracy Studies (QUADAS-2) to assess the quality. We extracted valuable information from eligible studies. Using a Bayesian bivariate model, we pooled sensitivity and specificity values and summary receiver operating characteristic (SROC) curves.ResultsFive articles, involving 428 participants at various stages of CKD were included. Three studies diagnosed by the cross-sectional area (CSA) of the rectus femoris, while two others by muscle thickness (MT) and shear wave elastography (SWE) from the same muscle, separately. Overall, CSA or SWE had a pooled sensitivity of 0.95 (95% CrI, 0.80, 1.00), and the specificity was 0.73 (95% CrI, 0.55, 0.88) for diagnosing sarcopenia in CKD patients.ConclusionsUltrasound measurements of CSA and SWE were more sensitive for diagnosing sarcopenia in the CKD population than in the general population. Ultrasound assessment from a single peripheral skeletal muscle site may serve as a rapid screening tool for identifying sarcopenic individuals within the CKD population, if a specific cut-off value could be determined.

The role of advanced glycation end products in sarcopenia in CKD patients

The accumulation of glycation end products (AGEs) is closely related to chronic inflammation, oxidative stress and can affect muscle function. An increase of the concentration of AGEs in the serum can be observed in patients already at the initial stages of the formation of chronic kidney disease (CKD). At the same time, there is no need for a violation of carbohydrate tolerance or diabetes mellitus. Sarcopenia is one of the complications of CKD. Its development in CKD can be considered not only as a result of endogenous intoxication, but also as one of the variants of premature aging. This literature review is devoted to the analysis of the mechanisms of the influence of AGEs on the occurrence and progression of sarcopenia in CKD.

Nutritional Strategies to Prevent Muscle Loss and Sarcopenia in Chronic Kidney Disease: What Do We Currently Know?

Loss of muscle mass is an extremely frequent complication in patients with chronic kidney disease (CKD). The etiology of muscle loss in CKD is multifactorial and may depend on kidney disease itself, dialysis, the typical chronic low-grade inflammation present in patients with chronic kidney disease, but also metabolic acidosis, insulin resistance, vitamin D deficiency, hormonal imbalances, amino acid loss during dialysis, and reduced dietary intake. All these conditions together increase protein degradation, decrease protein synthesis, and lead to negative protein balance. Aging further exacerbates sarcopenia in CKD patients. Nutritional therapy, such as protein restriction, aims to manage uremic toxins and slow down the progression of CKD. Low-protein diets (LPDs) and very low-protein diets (VLPDs) supplemented with amino acids or ketoacids are commonly prescribed. Energy intake is crucial, with a higher intake associated with maintaining a neutral or positive nitrogen balance. Adequate nutritional and dietary support are fundamental in preventing nutritional inadequacies and, consequently, muscle wasting, which can occur in CKD patients. This review explores the causes of muscle loss in CKD and how it can be influenced by nutritional strategies aimed at improving muscle mass and muscle strength.

DETERMINANT FACTORS OF SARCOPENIA AMONG PRE-DIALYSIS OUTPATIENTS IN A MALAYSIAN TERTIARY CARE CENTRE

Sarcopenia is an ageing condition characterised by a progressive and generalised loss of skeletal muscle mass and function. However, sarcopenia is not always related to advanced age in chronic kidney disease (CKD) but rather a consequence of accelerated protein catabolism. This study aimed to identify the prevalence of sarcopenia and its associated risk factors in pre-dialysis CKD patients. This cross-sectional study was conducted among 250 pre-dialysis CKD patients aged 18 years or older who attended the outpatient Renal Clinic in a tertiary hospital between April to November 2019. It was found that 59.2% of pre-dialysis CKD patients had slow gait speed, 52% had low handgrip strength, and 5.2% had low appendicular skeletal muscle mass index. The prevalence of sarcopenia in the studied group based on AWGS criteria was 5.2%, for which CKD stage 3-5 accounts for 0.4%, 0.8%, and 4% of the prevalence, respectively. Body mass index (AOR: 0.39, 95% CI: 0.166-0.912) and Modified Barthel Index score (AOR: 0.64, 95% CI: 0.470-0.884) were significantly associated with sarcopenia.to conclude, sarcopenia is prevalent in advanced-stage CKD and is related to low body mass index and a lack of functional independence. Controlling these two factors may delay sarcopenia progression in CKD patients. Given this, there is an urgent need to develop preventative and therapeutic approaches given the detrimental effects of sarcopenia on significant health outcomes in the CKD population. The effectiveness of dietary and exercise therapies to prevent sarcopenia in CKD should be explored.

Sarcopenia in chronic kidney disease: from bench to bedside.

Sarcopenia is a condition characterized by a loss of muscle mass and function. In chronic kidney disease (CKD), where a chronic catabolic state exists, sarcopenia commonly occurs through various mechanisms, resulting in muscle wasting and decreased muscle endurance. Sarcopenic patients with CKD have high morbidity and mortality rates. Indeed, the prevention and treatment of sarcopenia are mandatory. An imbalance between protein synthesis and degradation in muscle and increased oxidative stress and inflammation persist in CKD and induce muscle wasting. In addition, uremic toxins negatively affect muscle maintenance. A variety of potential therapeutic drugs targeting these muscle-wasting mechanisms in CKD have been investigated, but most of the trials focused on aged patients without CKD, and none of these drugs have been approved for the treatment of sarcopenia so far. Further studies on the molecular mechanisms of sarcopenia in CKD and targets for potential therapeutics are needed to improve the outcomes of sarcopenic patients with CKD.

Frequency and Clinical Impact of Anticholinergic Burden in older patients: Comparing older patients with and without chronic kidney disease

AimThis study aimed to determine the frequency and impact of anticholinergic burden in older adults with chronic kidney disease (CKD) and compare the results to older adults without CKD. MethodAge- and sex-matched older adults (age ≥60) were selected from a total cohort of 1557 subjects, and grouped as CKD (n = 589) and Non-CKD (n = 589). Groups were compared for the frequency, type of anticholinergic agents, and their effects on comprehensive geriatric assessment parameters. The anticholinergic burden was assessed using the anticholinergic burden (ACB) scale. An ACB of ≥2 was categorized as high anticholinergic burden. ResultsThe mean age of the partients was 81±6, and 66% were female. More patients in the CKD group experienced a high anticholinergic burden (45%, versus 38%, p = 0.015). Patients with CKD were more likely to receive beta blocker (25% versus 19%, p = 0.018), diuretic (19% versus 6%, p<0.001), while those who did not have CKD were more likely to be treated with dopaminergic agents (8% versus 12%, p = 0.039). A high anticholinergic burden was associated with sarcopenia (OR 1.62, 95% CI 1.10–2.38, p = 0.015), geriatric depression scale (OR 1.50, 95% CI 1.02–2.20, p = 0.037), and polypharmacy (OR 4.05, 95% CI 2.38–6.90, p<0.001), after adjustment for age, sex and comorbidities in the CKD group (p<0.05). ConclusionOlder patients with CKD are more likely to be exposed to drugs with anticholinergic effects, but have less clinical implications than those without CKD. A high anticholinergic burden is associated with polypharmacy, depression and sarcopenia in CKD.

Phosphate depletion in insulin-insensitive skeletal muscle drives AMPD activation and sarcopenia in chronic kidney disease.

Sarcopenia is a common and devastating condition in patients with chronic kidney disease (CKD). Here, we provide evidence that the kidney-muscle crosstalk in sarcopenia is mediated by reduced insulin sensitivity and the activation of the muscle-specific isoform of AMP deaminase, AMPD1. By using a high protein-based CKD model of sarcopenia in mice and differentiated human myotubes, we show that urea reduces insulin-dependent glucose and phosphate uptake by the skeletal muscle, thus contributing to the hyperphosphatemia observed in CKD whereas depleting intramuscular phosphate needed to restore energy and inhibit AMPD1. Hyperactivated AMPD1, in turn, aggravates the low energy state in the muscle by removing free adenosine monophosphate (AMP) and producing proinflammatory factors and uric acid which contribute to the progression of kidney disease. Our data provide molecular and metabolic evidence supporting the use of strategies aimed to improve insulin sensitivity and to block AMPD1 to prevent sarcopenia in subjects with CKD.

Sarcopenia and sarcopenic obesity in chronic kidney disease: update on prevalence, outcomes, risk factors and nutrition treatment.

This review summarizes literature from the last 18 months reporting on sarcopenia (or its components) in chronic kidney disease (CKD). The prevalence of sarcopenia in CKD is reported to be 5-62.5%, with higher rates observed later in the disease. Sarcopenic obesity rates are reported to be 2-23%. Sarcopenia in CKD is associated with increased risk of mortality, cardiovascular disease and vascular calcification. Risk factors include kidney disease itself and the impacts of CKD on lifestyle (reduced physical activity, diet changes). In earlier stages of CKD, if the risks from sarcopenia outweigh the risk of reaching end-stage renal disease, ensuring adequate energy intake combined with modest protein liberalization and physical activity may be indicated. Protein intakes above 1.3 g/kg of body weight per day should be avoided. For dialysis patients, interventions that provide a combination of carbohydrate, protein and fat appear more effective than those that provide protein alone, though it may take as long as 48 weeks for detectable changes in muscle mass. Sarcopenia is prevalent in CKD as kidney disease significantly impacts muscle mass and function. Nutrition interventions can improve components of sarcopenia, with an emphasis on adequate energy and protein.

Sarcopenia in chronic kidney disease: prevalence by different definitions and relationship with adiposity.

This was a cross-sectional study with chronic kidney disease (CKD) patients under non-dialysis-dependent (NDD), hemodialysis (HD), and kidney transplant (KTx) treatment aimed to evaluate the prevalence of sarcopenia using the European Working Group on Sarcopenia in Older People (EWGSOP2) and the Foundation for the National Institutes of Health (FNIH) guidelines, and to analyze the relationship between sarcopenia and its components and body adiposity. Body composition was assessed by dual-energy X-ray absorptiometry and anthropometry. Bioelectrical impedance provided data on the phase angle and body water. The prevalence of sarcopenia in the total sample (n=243; 53% men, 48±10 years) was 7% according to the FNIH and 5% according to the EWGSOP2 criteria, and was low in each CKD group independently of the criteria applied (maximum 11% prevalence). Low muscle mass was present in 39% (FNIH) and 36% (EWGSOP2) and dynapenia in 10% of the patients. Patients who were sarcopenic according to the EWGSOP2 criteria presented low body adiposity. Conversely, patients who were sarcopenic according to the FNIH criteria presented high adiposity. This study suggests that in CKD (i) sarcopenia and low muscle mass prevalence varies according to the diagnostic criteria; (ii) sarcopenia and low muscle mass are common conditions; (iii) the association with body adiposity depends on the criteria used to define low muscle mass; and (iv) the FNIH criteria detected higher adiposity in individuals with sarcopenia. Novelty: Prevalence of sarcopenia and low muscle mass in CKD varied according to the diagnostic criteria. Association of excess adiposity with sarcopenia and low muscle mass depends on muscle mass index applied. FNIH criteria detected higher adiposity in individuals with sarcopenia and low muscle mass.

Dietary Inflammatory Potential Is Associated With Sarcopenia Among Chronic Kidney Disease Population.

BackgroundSarcopenia, characterized by impaired muscle mass and function, is a common complication and the main reason for bad life quality and high mortality in chronic kidney disease (CKD). Limiting systemic inflammation is a potable intervention for sarcopenia. Dietary inflammatory potential can influence systemic inflammation. However, research about the association between dietary inflammatory potential and sarcopenia in CKD is limited.AimTo investigate the association between dietary inflammatory potential and sarcopenia in the CKD population.MethodsWe conducted a cross-section study based on the public database of the National Health and Nutrition Examination Survey (NHANES). In total, 2,569 adult CKD participants who had complete data for dietary inflammatory potential and sarcopenia were included. The dietary inflammatory potential was calculated by the dietary inflammation index (DII) score based on dietary recall interviews. We assessed sarcopenia via low skeletal muscle mass measured by dual-energy X-ray absorptiometry. Smooth curve fitting and a generalized linear mixed model were used to evaluate the relationship between DII and sarcopenia. Moreover, subgroup and sensitivity analyses were performed.ResultsThe overall prevalence of sarcopenia among patients with CKD is 19.11%. Smooth curve fitting results displayed that the DII score is near-linear positively associated with sarcopenia. Logistic regression confirmed sarcopenia is independently related to DII scores (odds ratio [OR], 1.17; 95% CI, 1.06–1.29). Subgroup analyses revealed relatively stronger associations between DII and sarcopenia among patients with CKD with other sarcopenia risk factors, such as hypoalbuminemia, low energy intake, low protein intake, and comorbidities.ConclusionThe dietary inflammatory potential is independently related to sarcopenia among patients with CKD. Anti-inflammatory diet patterns may be a protective intervention for CKD-associated sarcopenia.

MO956: Sarcopenia Predicts Mortality in Renal Transplant Candidates

Abstract BACKGROUND AND AIMS Sarcopenia is common in chronic kidney disease (CKD) and is associated with increased mortality and morbidity. Sarcopenia in CKD can be defined as a decreased muscle mass, mainly due to the catabolic state caused by the uremic environment. Malnutrition and inflammation are also common in sarcopenic patients. In this study, we aimed to investigate the prevalence of sarcopenia defined as low muscle mass determined by Psoas Muscle Index (PMI) in waitlisted end-stage renal disease (ESRD) patients and its association between ‘Prognostic Nutritional Index (PNI)’, ‘C-reactive protein (CRP) to Albumin Ratio (CAR)’ and mortality. METHOD ESRD patients registered to national kidney transplant waiting list and had abdomen CT at admission were included in the study. Kidney donor candidates were constituted as healthy controls. PMI ​​(cm2/m2) were calculated by proportioning the psoas muscle area detected in the abdomen CT with the square of the height. The PMI of the controls at the fifth percentile according to gender was accepted as the limit value for sarcopenia. PNI and CAR were calculated using albumin, CRP and absolute lymphocyte count. The associations between PMI, PNI, CAR and all-cause mortality were investigated. RESULTS A total of 162 ESRD patients and 87 age matched healthy controls were included in the study. The mean age of the patients was 44.7 ± 14.2 years and follow-up time was 3.37 (0.35–9.60) years. The mean PMI were similar between the groups (5.24 ± 1.71 versus 5.48 ± 1.87 cm2/m2 P = 0.302). While prevalence of sarcopenia (16.7% versus 3.4%, P = 0.002) and CAR [1.47 (0.12–37.10) versus 0.74 (0.21–10.20), P &amp;lt; 0.001] was higher; PNI [40 (20.4–52.2) versus 44 (36.1–53.0), P &amp;lt; 0.001] was lower in ESRD patients than controls. When ESRD patients compared according to sarcopenia PMI [3.45 ± 0.9 versus 5.59 ± 1.6, P &amp;lt; 0.001] and PNI [39 (20.4–51) versus 41 (23–52.2), P = 0.005] was significantly lower and CAR [2.03 (0.28–34.65) versus 1.28 (0.12–37.1), P = 0.041] was higher in sarcopenic ESRD group than non-sarcopenic ESRD group (Table 1). In the correlation analysis, PMI was positively correlated with PNI ​​(r = 0.246, P = 0.002), no correlated with CAR (r = −0.061, P = 0.445). In the follow-up, 67 waitlisted patients had been transplanted. In the five-year survival analysis, the non-sarcopenic transplant group [95% CI: 4.612–5.123 versus 95% CI: 2.721–5.413, P = 0.001] had better survival than sarcopenic transplant group (Figure 1). Mortality rates were similar in both sarcopenic transplant group and non-sarcopenic-non-transplant group. Multivariate regression analysis showed that sarcopenia (HR: 10.277, 95% CI: 3.912–27.000, P &amp;lt; 0.001), not having a transplant (HR: 3.949, 95% CI: 1.301–11.993, P = 0.015), low PNI (HR: 3.532, 95% CI: 1.303–9.574, P = 0.013) and duration of renal replacement therapy (HR: 1.009, 95% CI: 1.002–1.015, P = 0.008) were independent risk factors for mortality in all ESRD group. CONCLUSION In this study we observed that sarcopenia, as defined by low muscle mass, is almost seen five times more frequent in ESRD patients than controls and positively correlated with PNI. Sarcopenia is an independent risk factor for mortality in waitlisted patients.

Methylglyoxal Induces Inflammation, Metabolic Modulation and Oxidative Stress in Myoblast Cells.

Uremic sarcopenia is a serious clinical problem associated with physical disability and increased morbidity and mortality. Methylglyoxal (MG) is a highly reactive, dicarbonyl uremic toxin that accumulates in the circulatory system in patients with chronic kidney disease (CKD) and is related to the pathology of uremic sarcopenia. The pathophysiology of uremic sarcopenia is multifactorial; however, the details remain unknown. We investigated the mechanisms of MG-induced muscle atrophy using mouse myoblast C2C12 cells, focusing on intracellular metabolism and mitochondrial injury. We found that one of the causative pathological mechanisms of uremic sarcopenia is metabolic flow change to fatty acid synthesis with MG-induced ATP shortage in myoblasts. Evaluation of cell viability revealed that MG showed toxic effects only in myoblast cells, but not in myotube cells. Expression of mRNA or protein analysis revealed that MG induces muscle atrophy, inflammation, fibrosis, and oxidative stress in myoblast cells. Target metabolomics revealed that MG induces metabolic alterations, such as a reduction in tricarboxylic acid cycle metabolites. In addition, MG induces mitochondrial morphological abnormalities in myoblasts. These changes resulted in the reduction of ATP derived from the mitochondria of myoblast cells. Our results indicate that MG is a pathogenic factor in sarcopenia in CKD.

Sarcopenia in chronic kidney disease: prevalence and relationship with adiposity and fatigue

Rationale: The diagnosis of sarcopenia can be evaluated by several methods. Skeletal muscle metabolism changes also occur in obesity. Fatigue is present in chronic kidney disease (CKD). So, we evaluate the prevalence of sarcopenia using the revised guideline by The European Working Group on Sarcopenia in Older People (EWGSOP2) and by the Foundation of the National Institutes of Health (FNIH) in CKD; and analyze the relationship between sarcopenia, body adiposity and fatigue.

Effects of hormonal changes on sarcopenia in chronic kidney disease: where are we now and what can we do?

Sarcopenia or muscle wasting is a progressive and generalized skeletal muscle disorder involving the accelerated loss of muscle mass and function, often associated with muscle weakness (dynapenia) and frailty. Whereas primary sarcopenia is related to ageing, secondary sarcopenia happens independent of age in the context of chronic disease states such as chronic kidney disease (CKD). Sarcopenia has become a major focus of research and public policy debate due to its impact on patient's health‐related quality of life, health‐care expenditure, morbidity, and mortality. The development of sarcopenia in patients with CKD is multifactorial and it may occur independently of weight loss or cachexia including under obese sarcopenia. Hormonal imbalances can facilitate the development of sarcopenia in the general population and is a common finding in CKD. Hormones that may influence the development of sarcopenia are testosterone, growth hormone, insulin, thyroid hormones, and vitamin D. Although the relationship between free testosterone level that is low in uraemic patients and sarcopenia in CKD is not well‐defined, functional improvement may be seen. Unlike testosterone, it is known that vitamin D is associated with muscle strength, muscle size, and physical performance in patients with CKD. Outcomes after vitamin D replacement therapy are still controversial. The half‐life of growth hormone (GH) is prolonged in patients with CKD. Besides, IGF‐1 levels are normal in patients with Stage 4 CKD—a minimal reduction is seen in the end‐stage renal disease. Unresponsiveness or resistance of IGF‐1 and changes in the GH/IGF‐1 axis are the main causes of sarcopenia in CKD. Low serum T3 level is frequent in CKD, but the net effect on sarcopenia is not well‐studied. CKD patients develop insulin resistance (IR) from the earliest period even before GFR decline begins. IR reduces glucose utilization as an energy source by hepatic gluconeogenesis, decreasing muscle glucose uptake, impairing intracellular glucose metabolism. This cascade results in muscle protein breakdown. IR and sarcopenia might also be a new pathway for targeting. Ghrelin, oestrogen, cortisol, and dehydroepiandrosterone may be other players in the setting of sarcopenia. In this review, we mainly examine the effects of hormonal changes on the occurrence of sarcopenia in patients with CKD via the available data.

Advanced oxidation protein products contribute to chronic kidney disease-induced muscle atrophy by inducing oxidative stress via CD36/NADPH oxidase pathway.

BackgroundSarcopenia with chronic kidney disease (CKD) progression is associated with life prognosis. Oxidative stress has attracted interest as a trigger for causing CKD‐related muscular atrophy. Advanced oxidation protein products (AOPPs), a uraemic toxin, are known to increase oxidative stress. However, the role of AOPPs on CKD‐induced muscle atrophy remains unclear.MethodsIn a retrospective case–control clinical study, we evaluated the relationship between serum AOPPs levels and muscle strength in haemodialysis patients with sarcopenia (n = 26, mean age ± SEM: 78.5 ± 1.4 years for male patients; n = 22, mean age ± SEM: 79.1 ± 1.5 for female patients), pre‐sarcopenia (n = 12, mean age ± SEM: 73.8 ± 2.0 years for male patients; n = 4, mean age ± SEM: 74.3 ± 4.1 for female patients) or without sarcopenia (n = 12, mean age ± SEM: 71.3 ± 1.6 years for male patients; n = 7, mean age ± SEM: 77.7 ± 1.6 for female ). The molecular mechanism responsible for the AOPPs‐induced muscle atrophy was investigated by using 5/6‐nephrectomized CKD mice, AOPPs‐overloaded mice, and C2C12 mouse myoblast cells.ResultsThe haemodialysis patients with sarcopenia showed higher serum AOPPs levels as compared with the patients without sarcopenia. The serum AOPPs levels showed a negative correlation with grip strength (P < 0.01 for male patients, P < 0.01 for female patients) and skeletal muscle index (P < 0.01 for male patients). Serum AOPPs levels showed a positive correlation with cysteinylated albumin (Cys‐albumin), a marker of oxidative stress (r 2 = 0.398, P < 0.01). In the gastrocnemius of CKD mice, muscle AOPPs levels were also increased, and it showed a positive correlation with atrogin‐1 (r 2 = 0.538, P < 0.01) and myostatin expression (r 2 = 0.421, P < 0.05), but a negative correlation with PGC‐1α expression (r 2 = 0.405, P < 0.05). Using C2C12 cells, AOPPs increased atrogin‐1 and myostatin expression through the production of reactive oxygen species via CD36/NADPH oxidase pathway, and decreased myotube formation. AOPPs also induced mitochondrial dysfunction. In the AOPPs‐overloaded mice showed that decreasing running time and hanging time accompanied by increasing AOPPs levels and decreasing cross‐sectional area in gastrocnemius.ConclusionsAdvanced oxidation protein products contribute to CKD‐induced sarcopenia, suggesting that AOPPs or its downstream signalling pathway could be a therapeutic target for the treatment of CKD‐induced sarcopenia. Serum AOPPs or Cys‐albumin levels could be a new diagnostic marker for sarcopenia in CKD.

Resistance exercise and nutritional interventions for augmenting sarcopenia outcomes in chronic kidney disease: a narrative review.

Sarcopenia is an age‐related progressive muscle disease characterized by loss of muscle mass, muscle strength and physical performance with high prevalence in chronic kidney disease (CKD). CKD is associated with decreased muscle protein synthesis and muscle breakdown due to a number of factors including, the uremic inflammatory environment of the disease. CKD patients are highly sedentary and at risk of malnutrition which may exacerbate sarcopenia outcomes even further. Short and long‐term exercise and nutritional interventions have been studied and found to have some positive effects on sarcopenia measures in CKD. This narrative review summarized evidence between 2010 and 2020 of resistance exercise (RE) alone or combined with nutritional interventions for improving sarcopenia outcomes in CKD. Due to lack of CKD‐specific sarcopenia measures, the second European Working Group on Sarcopenia in Older People (EWGSOP2) definition has been used to guide the selection of the studies. The literature search identified 14 resistance exercise‐based studies and 5 nutrition plus RE interventional studies. Muscle strength outcomes were increased with longer intervention duration, intervention supervision, and high participant adherence. Data also suggested that CKD patients may require increased RE intensity and progressive loading to obtain detectable results in muscle mass. Unlike muscle strength and muscle mass, physical performance was readily improved by all types of exercise in long or short‐term interventions. Four studies used RE with high‐protein nutritional supplementation. These showed significant benefits on muscle strength and physical performance in dialysis patients while non‐significant results were found in muscle mass. More research is needed to confirm if a combination of RE and vitamin D supplementation could act synergistically to improve muscle strength in CKD. The current evidence on progressive RE for sarcopenia in CKD is encouraging; however, real‐life applications in clinical settings are still very limited. A multidisciplinary patient‐centred approach with regular follow‐up may be most beneficial due to the complexity of sarcopenia in CKD. Long‐term randomized control trials are needed to verify optimal RE prescription and explore safety and efficacy of other nutritional interventions in CKD.

Sarcopenia in chronic kidney disease – A brief review

Sarcopenia is a progressive age -related loss of muscle mass associated with a decline in muscle function and physical performance. Patients with chronic kidney disease experience substantial loss of muscle mass, weakness, and poor physical performance. Indeed, with the progression of chronic kidney disease, skeletal muscle dysfunction contributes to mobility limitation, loss of functional independence, and vulnerability to disease complications. There is a lack of robust data on the negative effect of the impact of kidney disease on skeletal muscle dysfunction, as well as on screening and treatment strategies that can be used in clinical practice to prevent functional decline and disability. Therefore, sarcopenia may be an underestimated condition with major implications for people with chronic kidney disease, even before the start of dialysis, which makes research into this topic necessary. The purpose of this review is to expand on some fundamental topics of sarcopenia, with an emphasis on the setting of chronic kidney disease patients.