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Clinical relevance of sarcopenia in chronic kidney disease.

ABSTRACT: In this article, we review sarcopenia in chronic kidney disease (CKD). We aim to present how definitions of sarcopenia from the general population may pertain to those with CKD, its assessment by clinicians and emerging therapies for sarcopenia in CKD. For this review, we limit our description and recommendations to patients with CKD who are not on dialysis.Poorer parameters of lean mass, strength and physical function are associated with worsening patient-centered outcomes such as limiting mobility, falls and mortality in CKD; however, the magnitude of these associations are different in those with and without CKD. Sarcopenia in CKD is a balance between skeletal muscle regeneration and catabolism, which are both altered in the uremic environment. Multiple pathways are involved in these derangements, which are briefly reviewed. Differences between commonly used terms cachexia, frailty, protein-energy wasting, dynapenia and sarcopenia are described. Therapeutic options in predialysis CKD are not well studied; therefore, we review exercise options and emerging pharmacological therapies.Sarcopenia, now with its own International Classification of Diseases, 10th Revision (ICD-10) code, is of importance clinically and should be accounted for in research studies in patients with CKD. Multiple therapies for sarcopenia are in development and will hopefully be available for our patients in the future.

SUBMITTER: Moorthi RN

PROVIDER: S-EPMC5860815 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Clinical relevance of sarcopenia in chronic kidney disease.

Moorthi Ranjani N RN Avin Keith G KG

Current opinion in nephrology and hypertension 20170501 3

<h4>Purpose of review</h4>In this article, we review sarcopenia in chronic kidney disease (CKD). We aim to present how definitions of sarcopenia from the general population may pertain to those with CKD, its assessment by clinicians and emerging therapies for sarcopenia in CKD. For this review, we limit our description and recommendations to patients with CKD who are not on dialysis.<h4>Recent findings</h4>Poorer parameters of lean mass, strength and physical function are associated with worseni ...[more]

PMID: 28198733

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Project description:BackgroundFrailty and sarcopenia are prevalent in chronic kidney disease (CKD) populations and could increase the risk for adverse health outcomes. Few studies assess the correlation between frailty, sarcopenia and CKD in non-dialysis patients. Therefore, this study aimed to determine frailty-associated factors in elderly CKD stage I-IV patients, expected to early identify and intervene in the frailty of elderly CKD patients.MethodsA total of 774 elderly CKD I-IV patients (>60 years of age) recruited from 29 clinical centers in China between March 2017 and September 2019 were included in this study. We established a Frailty Index (FI) model to evaluate frailty risk and verified the distributional property of FI in the study population. Sarcopenia was defined according to the criteria of the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression analysis was used to assess the associated factors for frailty.ResultsSeven hundred seventy-four patients (median age 67 years, 66.0% males) were included in this analysis, with a median estimated glomerular filtration rate of 52.8 mL/min/1.73 m2 . The prevalence of sarcopenia was 30.6%. The FI exhibited a right-skewed distribution. The age-related slope of FI was 1.4% per year on a logarithmic scale (r2 = 0.706, 95% CI 0.9, 1.8, P < 0.001). The upper limit of FI was around 0.43. The FI was related to mortality (HR = 1.06, 95% CI 1.00, 1.12, P = 0.041). Multivariate multinomial logistic regression analysis showed that sarcopenia, advanced age, CKD stage II-IV, low level of serum albumin and increased waist-hip ratio were significantly associated with high FI status, while advanced age and CKD stage III-IV were significantly associated with for median FI status. Moreover, the results from the subgroup were consistent with the leading results.ConclusionsSarcopenia was independently associated with an increased risk for frailty in elderly CKD I-IV patients. Patients with sarcopenia, advanced age, high CKD stage, high waist-hip ratio and low serum albumin level should be assessed for frailty.

Project description:Background Sarcopenia, 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. Aim To investigate the association between dietary inflammatory potential and sarcopenia in the CKD population. Methods We 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. Results The 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. Conclusion The 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.

Project description:There were few data regarding the association of volume status with sarcopenia using muscle mass, strength, and physical performance in non-dialysis chronic kidney disease (ND-CKD) patients. We aimed to evaluate the association between volume status and sarcopenia in ND-CKD patients. Our retrospective study analyzed data from a previous study which included ND-CKD patients who had stable renal function. Our study used its baseline data alone. The edema index and muscle mass were measured using a multi-frequency bioimpedance analysis machine. The edema index was calculated using extracellular water/total body water ratio. The skeletal muscle index (SMI, kg/m2) was calculated using appendicular muscle mass per height squared. Handgrip strength (HGS, kg) was measured during the standing position in all patients. Dynamic gait speed (GS, m/s) was evaluated using 6-m walking speed. Patients with both low muscle mass (SMI < 7.0 kg/m2 for men and < 5.7 kg/m2 for women using bioimpedance analysis) and low HGS (< 28 kg for men and < 18 kg for women) or low GS (< 1.0 m/s) were classified as having sarcopenia. The patients (n = 147) were divided into tertiles based on the edema index level. The mean edema index in the low, middle, and high tertiles was 0.377 ± 0.006, 0.390 ± 0.003, and 0.402 ± 0.006, respectively. The edema index was significantly correlated with SMI, HGS, and GS (r = - 0.343 for SMI, - 0.492 for HGS, and - 0.331 for GS; P < 0.001 for three indicators). The SMI, HGS, and GS values were 8.1 ± 1.0 kg/m2, 33.0 ± 9.4 kg, and 1.2 ± 0.2 m/s in the low tertile,7.8 ± 1.2 kg/m2, 30.0 ± 7.5 kg, and 1.0 ± 0.3 m/s in the middle tertile, and 7.2 ± 1.4 kg/m2, 23.7 ± 7.4 kg, and 1.0 ± 0.3 m/s in the high tertile, respectively. Univariate analyses revealed that SMI was lower in patients in the high tertile than in those in the low tertile. HGS was lowest in high tertile, and GS was greatest in the low tertile. The high tertile for predicting sarcopenia had an odds ratio of 6.03 (95% CI, 1.78-20.37; P = 0.004) compared to low or middle tertiles. The results of multivariate analyses were similar to those of the univariate analyses. The subgroup analyses showed that statistical significance was greater in < 65 years and men than ≥ 65 years and women. The present study showed that the edema index is inversely associated with sarcopenia, muscle mass index, strength, and physical performance in ND-CKD patients. However, considering the limitations of our study such as its small sample size, this association was not strong. Further studies that include volume-independent measurements, data on physical activity and diet, and a larger number of patients are warranted to overcome these limitations.

Project description:BackgroundThe mortality of dialysis patients greatly exceeds that of the general population and identifying predictive factors for mortality may provide opportunities for earlier intervention. This study assessed the influence of sarcopenia on mortality in patients on haemodialysis.MethodsThis prospective, observational study enrolled 77 haemodialysis patients aged 60 years and over, of whom 33 (43%) were female, from two community dialysis centres. Baseline demographic and laboratory data were collected, and sarcopenia was diagnosed using grip strength, muscle mass by bioimpedance analysis (BIA) and muscle function by timed up-and-go according to European Working Group on Sarcopenia in Older People criteria. Nutritional status was assessed using a subjective nutritional assessment score, comprising functional changes in weight, appetite, gastrointestinal symptoms and energy.. A comorbidity score (maximum 7 points) was derived from the presence or absence of hypertension, ischaemic heart disease, vascular disease (cerebrovascular disease, peripheral vascular disease, and abdominal aortic aneurysm), diabetes mellitus, respiratory disease, a history of malignancy and psychiatric disease. Outcomes over six years were linked to the Australian and New Zealand Dialysis and Transplant Registry.ResultsThe median participant age was 71 years (range 60-87). Probable and confirmed sarcopenia was present in 55.9% and severe sarcopenia with reduced functional testing in 11.7%. Over 6 years, overall mortality was 50 of the 77 patients (65%), principally from cardiovascular events, dialysis withdrawal and infection. There were no significant survival differences between patients with no, probable, confirmed, or severe sarcopenia, or between tertiles of the nutritional assessment score. After adjustment for age, dialysis vintage, mean arterial pressure (MAP) and the total comorbidity score, no sarcopenia category predicted mortality. However, the total comorbidity score [Hazard Ratio (HR) 1.27, Confidence Intervals (CI) 1.02, 1.58, p = 0.03] and MAP (HR 0.96, CI 0.94, 0.99, P = < 0.01) predicted mortality.ConclusionSarcopenia is highly prevalent in elderly haemodialysis patients but is not an independent predictor of mortality. Haemodialysis patients have multiple competing risks for mortality which, in this study, was predicted by a lower MAP and a higher total comorbidity score.Trial registrationRecruitment commenced December 2011. The study was registered 10.01.2012 with the Australian New Zealand Clinical Trials Registry (ACTRN12612000048886).

Project description:BackgroundConventional definitions of sarcopenia based on lean mass may fail to capture low lean mass relative to higher fat mass, that is, relative sarcopenia. The objective of this study is to determine the associations of sarcopenia and relative sarcopenia with mortality independent of co-morbidities, and whether chronic kidney disease (CKD) and adiposity alter these associations.MethodsDual energy X-ray absorptiometry-derived appendicular lean mass index (ALMI, kg/m2 ) and fat mass index (FMI, kg/m2 ) were assessed in 14 850 National Health and Nutrition Examination Survey participants from 1999 to 2006 and were linked to death certificate data in the National Death Index with follow-up through 2011. Sarcopenia was defined using sex-specific and race/ethnicity-specific standard deviation scores compared with young adults (T-scores) as an ALMI T-score < -2 and relative sarcopenia as fat-adjusted ALMI (ALMIFMI ) T-score < -2. Glomerular filtration rate (GFR) was estimated using creatinine-based (eGFRCr ) and cystatin C-based (eGFRCys ) regression equations.ResultsThree (3.0) per cent of National Health and Nutrition Examination Survey participants met criteria for sarcopenia and 8.7% met criteria for relative sarcopenia. Sarcopenia and relative sarcopenia were independently associated with mortality (HR sarcopenia 2.20, 95% CI 1.69 to 2.86; HR relative sarcopenia 1.60, 95% CI 1.31 to 1.96). The corresponding population attributable risks were 5.2% (95% CI 3.4% to 6.4%) and 8.4% (95% CI 4.8% to 11.2%), respectively. Relative sarcopenia remained significantly associated with mortality (HR 1.32, 95% CI 1.08 to 1.61) when limited to the subset who did not meet the criteria for sarcopenia. The risk of mortality associated with relative sarcopenia was attenuated among persons with higher FMI (P for interaction <0.01) and was not affected by CKD status for either sarcopenia or relative sarcopenia.ConclusionsSarcopenia and relative sarcopenia are significantly associated with mortality regardless of CKD status. Relative sarcopenia is nearly three-fold more prevalent amplifying its associated mortality risk at the population level. The association between relative sarcopenia and mortality is attenuated in persons with higher FMI.

Project description:BackgroundChronic kidney disease (CKD) patients experience skeletal muscle wasting and decreased exercise endurance. Our previous study demonstrated that indoxyl sulfate (IS), a uremic toxin, accelerates skeletal muscle atrophy. The purpose of this study was to examine the issue of whether IS causes mitochondria dysfunction and IS-targeted intervention using AST-120, which inhibits IS accumulation, or mitochondria-targeted intervention using L-carnitine or teneligliptin, a dipeptidyl peptidase-4 inhibitor which retains mitochondria function and alleviates skeletal muscle atrophy and muscle endurance in chronic kidney disease mice.MethodsThe in vitro effect of IS on mitochondrial status was evaluated using mouse myofibroblast cells (C2C12 cell). The mice were divided into sham or 5/6-nephrectomized (CKD) mice group. Chronic kidney disease mice were also randomly assigned to non-treatment group and AST-120, L-carnitine, or teneligliptin treatment groups.ResultsIn C2C12 cells, IS induced mitochondrial dysfunction by decreasing the expression of PGC-1α and inducing autophagy in addition to decreasing mitochondrial membrane potential. Co-incubation with an anti-oxidant, ascorbic acid, L-carnitine, or teneligliptine restored the values to their original state. In CKD mice, the body and skeletal muscle weights were decreased compared with sham mice. Compared with sham mice, the expression of interleukin-6 and atrophy-related factors such as myostatin and atrogin-1 was increased in the skeletal muscle of CKD mice, whereas muscular Akt phosphorylation was decreased. In addition, a reduced exercise capacity was observed for the CKD mice, which was accompanied by a decreased expression of muscular PCG-1α and increased muscular autophagy, as reflected by decreased mitochondria-rich type I fibres. An AST-120 treatment significantly restored these changes including skeletal muscle weight observed in CKD mice to the sham levels accompanied by a reduction in IS levels. An L-carnitine or teneligliptin treatment also restored them to the sham levels without changing IS level.ConclusionsOur results indicate that IS induces mitochondrial dysfunction in skeletal muscle cells and provides a potential therapeutic strategy such as IS-targeted and mitochondria-targeted interventions for treating CKD-induced muscle atrophy and decreased exercise endurance.

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Clinical relevance of sarcopenia in chronic kidney disease.

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Clinical relevance of sarcopenia in chronic kidney disease.

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