Making the invisible visible: imaging techniques for assessing muscle mass and muscle quality in chronic kidney disease.

Muscle wasting and low muscle mass are prominent features of protein energy wasting (PEW), sarcopenia and sarcopenic obesity in patients with chronic kidney disease (CKD). In addition, muscle wasting is associated with low muscle strength, impaired muscle function and adverse clinical outcomes such as low quality of life, hospitalizations and increased mortality. While assessment of muscle mass is well justified, the assessment of skeletal muscle should go beyond quantity. Imaging techniques provide the means for non-invasive, comprehensive, in-depth assessment of the quality of the muscle such as the infiltration of ectopic fat. These techniques include computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Dual energy X-ray absorptiometry is also an imaging technique, but one that only provides quantitative and not qualitative data on muscle. The main advantage of imaging techniques compared with other methods such as bioelectrical impedance analysis and anthropometry is that they offer higher precision and accuracy. On the other hand, the higher cost for acquiring and maintaining the imaging equipment, especially CT and MRI, makes these less-used options and available mostly for research purposes. In the field of CKD and end-stage kidney disease (ESKD), imaging techniques are gaining attention for evaluating muscle quantity and more recently muscle fat infiltration. This review describes the potential of these techniques in CKD and ESKD settings for muscle assessment beyond that of muscle quantity.

Factors associated with variability in skeletal muscle radiodensity in patients with metastatic cancer.

OBJECTIVES: This study aimed to explore factors associated with skeletal muscle radiodensity (SMD) variability in patients with metastatic cancer. METHODS: This study included 393 patients (median age 61 y, 70% women) who had computed tomography (CT) scans within 30 days of inclusion in the study. SMD was evaluated from CT by averaging the Hounsfield unit value of the total muscle area. Skeletal muscle index (SMI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and total adipose tissue index (TATI) were also assessed by CT. Additionally, age, sex, race/skin color, disease characteristics, comorbidities, inflammatory markers, handgrip strength (HGS), and body mass index (BMI) were recorded and evaluated in the linear regression analysis to identify factors associated with SMD variability. RESULTS: Multivariate explanatory models having SMD as an independent variable were performed and included BMI (model 1, r2 = 0.699), TATI (model 2, r2 = 0.712) or VATI and SATI (model 3, r2 = 0.706) in addition to age, race/skin color, tumor site, kidney disease, serum albumin, HGS, and SMI as dependent variables. For all models, lower SMD was associated with higher age, BMI, and adiposity measurements, kidney disease, White race/skin color, and lower serum albumin, HGS, and SMI. The primary tumor site also contributed to changes in SMD in all models, specifically those located in the gastrointestinal tract, gynecologic, and bone and connective tissue. CONCLUSION: In this group of patients with metastatic cancer, lower SMD was associated with older age, White race/skin color, and an overall worse clinical condition.

Sarcopenia diagnosed by ultrasound-assessed quadriceps muscle thickness and handgrip strength predicts mortality in patients on hemodialysis.

BACKGROUND: Estimation of muscle mass is a pivotal component in the diagnosis of protein-energy wasting and sarcopenia. While bioimpedance spectroscopy is a widely  accepted technique for the assessment of lean tissue related to the diagnosis of sarcopenia, to date skeletal muscle ultrasound (US) has not gained full acceptance for this purpose. The aim of this study was to assess the predictive value for mortality of the indexed thickness of the quadriceps vastus intermedius, as measured by US, compared to lean tissue index as estimated by bioimpedance spectroscopy, both combined with handgrip strength in a group of patients with end-stage kidney disease (ESKD) on maintenance hemodialysis (HD). METHODS: The cut-off values for low handgrip strength were < 27 kg for males and < 16 kg for females. The cut-off value for low lean tissue index was obtained from an age-matched healthy control group, with low lean tissue index being defined as values below the 10th percentile of the distribution of healthy subjects. The cut-off values for low quadriceps vastus intermedius thickness index were < 3.44 mm/m2 for males and < 3.52 mm/m2 for females. RESULTS: Ultrasound and bioimpedance spectroscopy were performed in 99 patients, and handgrip strength was assessed in 64 patients, all on maintenance HD. After a median follow-up of 28 months (interquartile range 19-41 months) 38 patients died. Lean tissue index was not associated with mortality, while low quadriceps vastus intermedius thickness index and low handgrip strength were associated with an increased hazard of death. In the fully adjusted model, only the combination of low handgrip strength and low quadriceps vastus intermedius thickness index was significantly associated with higher mortality. CONCLUSION: When combined with low handgrip strength, low quadriceps muscle US outperformed low lean tissue index as assessed by bioimpedance spectroscopy in predicting mortality in a cohort of patients on maintenance HD. Ultrasound may be a useful and convenient technique for the assessment of sarcopenia and protein-energy wasting in this patient population.

Needs, barriers and facilitators for a healthier lifestyle in haemodialysis patients: The GoodRENal project.

BACKGROUND: Malnutrition, sedentary lifestyle, cognitive dysfunction and poor psychological well-being are often reported in patients on haemodialysis (HD). AIMS: We aimed to explore needs, barriers and facilitators-as perceived by patients, their carers, and healthcare professionals (HCPs) for increasing the adherence to the diet, to physical activity and cognition and psychological well-being. METHODS: This is an observational cross-sectional study following the STROBE statement. This study is part of an ERASMUS+ project, GoodRENal-aiming to develop digital tools as an educational approach to patients on HD. For that, the GoodRENal comprises HD centers located in four Belgium, Greece, Spain and Sweden. Exploratory questionnaires were developed regarding the perceived needs, barriers and facilitators regarding the diet, physical activity, cognition and psychological well-being from the perspective of patients, their carers and HCPs. RESULTS: In total, 38 patients, 34 carers and 38 HCPs were included. Nutrition: For patients and carers, the main needs to adhere to the diet included learning more about nutrients and minerals. For patients, the main barrier was not being able to eat what they like. Physical activity: As needs it was reported information about type of appropriate physical activity, while fatigue was listed as the main barrier. For Cognitive and emotional state, it was perceived as positive for patients and carers perception but not for HCPs. The HCPs identified as needs working as a team, having access to specialised HCP and being able to talk to patients in private. CONCLUSIONS: Patients and their carers listed as needs guidance regarding nutrition and physical activity but were positive with their cognitive and emotional state. The HCPs corroborated these needs and emphasised the importance of teamwork and expert support.

Ultraprocessed foods and chronic kidney disease-double trouble.

High energy intake combined with low physical activity generates positive energy balance, which, when maintained, favours obesity, a highly prevalent morbidity linked to development of non-communicable chronic diseases, including chronic kidney disease (CKD). Among many factors contributing to disproportionately high energy intakes, and thereby to the obesity epidemic, the type and degree of food processing play an important role. Ultraprocessed foods (UPFs) are industrialized and quite often high-energy-dense products with added sugar, salt, unhealthy fats and food additives formulated to be palatable or hyperpalatable. UPFs can trigger an addictive eating behaviour and is typically characterized by an increase in energy intake. Furthermore, high consumption of UPFs, a hallmark of a Western diet, results in diets with poor quality. A high UPF intake is associated with higher risk for CKD. In addition, UPF consumption by patients with CKD is likely to predispose and/or to exacerbate uraemic metabolic derangements, such as insulin resistance, metabolic acidosis, hypertension, dysbiosis, hyperkalaemia and hyperphosphatemia. Global sales of UPFs per capita increased in all continents in recent decades. This is an important factor responsible for the nutrition transition, with home-made meals being replaced by ready-to-eat products. In this review we discuss the potential risk of UPFs in activating hedonic eating and their main implications for health, especially for kidney health and metabolic complications of CKD. We also present various aspects of consequences of UPFs on planetary health and discuss future directions for research to bring awareness of the harms of UPFs within the CKD scenario.

The dietary source of trimethylamine N-oxide and clinical outcomes: an unexpected liaison.

The profile of gut microbiota can vary according to host genetic and dietary characteristics, and be influenced by disease state and environmental stressors. The uremic dysbiosis results in a loss of biodiversity and overgrowth of microorganisms that may cause elevation of metabolic solutes such as trimethylamine N-oxide (TMAO), inducing pathogenic effects on its host. In patients with chronic kidney disease (CKD), TMAO levels are elevated because of a decreased clearance and an increased production from the uremic gut dysbiosis with a disrupted intestinal barrier and elevated enzymatic hepatic activity. Dietary precursors of TMAO are abundant in animal-derived foods such as red meat, egg yolk and other full-fat dietary products. TMAO is also found naturally in fish and certain types of seafood, with the TMAO content highly variable according to the depth of the sea where the fish is caught, as well as processing and storage. Although evidence points towards TMAO as being an important link to vascular damage and adverse cardiovascular outcomes, the evidence in CKD patients has not been consistent. In this review we discuss the potential dietary sources of TMAO and its actions on the intestinal microbiome as an explanation for the divergent results. We further highlight the potential of a healthy diet as one feasible therapeutic opportunity to prevent gut dysbiosis and reduce uremic toxin levels in patients with CKD.

From ultra-processed foods towards healthy eating for CKD patients: a proposal of educational infographics.

Ultraprocessed food (UPF) is defined as industrialized, packaged and ready-to-eat food produced on a large scale, using sophisticated industrial machinery. Examples of UPFs include salty and sweet snacks, industrialized biscuits and packaged meals, processed meats and sugary drinks. Ultraprocessed food has a long-shelf life, is highly palatable, microbiologically safe, affordable and most of all, easy to consume. For these reasons, its consumption has been increasing worldwide, and is replacing healthy homemade meals. The main concern of this dietary shift is that UPFs come with the addition of salt, sugar, unhealthy fats, and several additives and taste enhancers that contain, among other substances, relevant quantities of potassium, phosphate and sodium. A large proportion of UPF in the diet may carry risks for patients with chronic kidney disease (CKD) since it can worsen blood pressure and glycemic control, and lead to constipation, hyperkalemia and hyperphosphatemia. Acknowledging the importance of UPF in kidney health implies integrating nutritional counseling with information on UPFs, and specific educational material can be helpful for patients, caregivers, and also for health care providers. We developed a set of 3 infographics dedicated to CKD patients, with information on how to identify UPFs, reasons for decreasing consumption, how to compose a healthy CKD plate and tips for reading food labels in supermarkets and grocery shops. We hope that this material can be useful in CKD outpatient clinics and dialysis centers as well as in general practitioners' offices, caring for early stage CKD.

New Insights Into Dietary Approaches to Potassium Management in Chronic Kidney Disease.

Potassium disorders are one of the most common electrolyte abnormalities in patients with chronic kidney disease (CKD), contributing to poor clinical outcomes. Maintaining serum potassium levels within the physiologically normal range is critically important in these patients. Dietary potassium restriction has long been considered a core strategy for the management of chronic hyperkalemia in patients with CKD. However, this has been challenged by recent evidence suggesting a paradigm shift toward fostering more liberalized, plant-based dietary patterns. The advent of novel potassium binders and an improved understanding of gastrointestinal processes involved in potassium homeostasis (e.g., gastrointestinal potassium wasting) may facilitate a paradigm shift and incorporation of heart-healthy potassium-enriched food sources. Nevertheless, uncertainty regarding the risk-benefit of plant-based diets in the context of potassium management in CKD remains, requiring well-designed clinical trials to determine the efficacy of dietary potassium manipulation toward improvement of clinical outcomes in patients with CKD.

Design and methodology of the SARCopenia trajectories and associations with adverse clinical outcomes in patients on HemoDialysis: the SARC-HD study.

BACKGROUND: Sarcopenia has been associated with adverse outcomes in patients with chronic kidney disease (CKD), particularly in those undergoing hemodialysis (HD). However, the trajectories across sarcopenia stages, their determinants, and associations with adverse clinical outcomes have yet to be comprehensively examined. METHODS: The SARC-HD is a multicenter, observational prospective cohort study designed to comprehensively investigate sarcopenia in patients on HD. Eligibility criteria include adult patients undergoing HD for ≥ 3 months. The primary objective is to investigate the trajectories of sarcopenia stages and their potential determinants. Secondary objectives include evaluating the association between sarcopenia and adverse clinical outcomes (i.e., falls, hospitalization, and mortality). Sarcopenia risk will be assessed by the SARC-F and SARC-CalF questionnaire. Sarcopenia traits (i.e., low muscle strength, low muscle mass, and low physical performance) will be defined according to the revised European Working Group on Sarcopenia in Older People and will be assessed at baseline and after 12 follow-up months. Patients will be followed-up at 3 monthly intervals for adverse clinical outcomes during 24 months. DISCUSSION: Collectively, we expect to provide relevant clinical findings for healthcare professionals from nephrology on the association between sarcopenia screening tools (i.e., SARC-F and SARC-CalF) with objective sarcopenia measurements, as well as to investigate predictors of trajectories across sarcopenia stages, and the impact of sarcopenia on adverse clinical outcomes. Hence, our ambition is that the data acquired from SARC-HD study will provide novel and valuable evidence to support an adequate screening and management of sarcopenia in patients on HD.

Sarcopenic obesity and its relation with muscle quality and mortality in patients on chronic hemodialysis.

BACKGROUND & AIMS: Sarcopenia is prevalent in patients with end-stage kidney disease (ESKD) on hemodialysis (HD), and is associated with poor outcomes, while obesity may be protective. Sarcopenic obesity is associated with increased frailty, morbidity and mortality in the general population. Myosteatosis, i.e., muscle fat infiltration, has major effects on muscle strength and physical performance, but is poorly investigated in the nephrology setting. In the present study we aimed to assess the association between sarcopenic obesity, as diagnosed by abdominal CT, and mortality. Moreover, the relationship between myosteatosis, sarcopenic obesity and mortality was also investigated. METHODS: This is a retrospective study in which ESKD patients on HD submitted to unenhanced abdominal CT for clinical reasons at least 6 months after dialysis initiation were evaluated for sarcopenic obesity and myosteatosis, defined as intermuscular fat area and low attenuation muscle area. Sarcopenic obesity was diagnosed in cases of low abdominal skeletal muscle area and high total fat area. Receiver-operating characteristics (ROC) analysis with Youden index was used to determine the cut-off for high total fat area. Intermuscular fat area and low attenuation muscle area were evaluated by applying the Hounsfield unit of interest (-190; -30, and -29; +29 respectively). Cox regression analysis was used to evaluate the association between predictors and mortality risk. RESULTS: We enrolled 212 patients, aged 68.8 (±14.7) years, 65.5% (139/212) male. Median follow-up was 19.7 (interquartile range [IQR] 2.7-35) months. Sarcopenic obesity was diagnosed in 19.8% of patients and was associated with increased mortality (HR: 3.29 (1.72; 6.27), P < 0.001), and with the presence of myosteatosis. Both intermuscular fat area and low attenuation muscle area were associated with increased mortality in adjusted analyses. CONCLUSIONS: Patients with sarcopenic obesity have increased myosteatosis. Sarcopenic obesity and myosteatosis are associated with increased mortality in patients on HD.

GLIM in chronic kidney disease: What do we need to know?

The lack of consensus on diagnostic criteria for malnutrition has hampered developments in research and clinical practice pertaining to nutrition. This opinion paper describes the applicability and other aspects of using the Global Leadership Initiative on Malnutrition (GLIM) criteria for diagnosing malnutrition in patients with chronic kidney disease (CKD). We examine the purpose of GLIM, the particularities of CKD that can affect the nutritional and metabolic status and the diagnosis of malnutrition. In addition, we make an appraisal of previous studies that used GLIM in the context of CKD and discuss the value and relevance of using the GLIM criteria in patients with CKD.

Central obesity as assessed by conicity index and a-body shape index associates with cardiovascular risk factors and mortality in kidney failure patients.

Background: Anthropometric indices of central obesity, waist circumference (WC), conicity index (CI), and a-body shape index (ABSI), are prognostic indicators of cardiovascular (CV) risk. The association of CI and ABSI with other CV risk indices, markers of nutritional status and inflammation, and clinical outcomes in chronic kidney disease (CKD) stage 5 (CKD5) patients was investigated. Methods: In a cross-sectional study with longitudinal follow up of 203 clinically stable patients with CKD5 (median age 56 years; 68% males, 17% diabetics, 22% with CV disease, and 39% malnourished), we investigated CI and ABSI and their associations with atherogenic index of plasma (AIP), Framingham CV risk score (FRS), Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC), handgrip strength (HGS), high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). CV events (CVE) and all-cause mortality during up to 10-years follow up were analyzed by multivariate survival analysis of restricted mean survival time (RMST). Results: Chronic kidney disease patients with middle and highest CI and ABSI tertiles (indicating greater abdominal fat deposition), compared to those with the lowest CI and ABSI tertiles, tended to be older, more often men and diabetic, had significantly higher levels of hsCRP, IL-6, AIP, FRS, CAC and AVC scores. CI and ABSI were positively correlated with CAC, FRS, AIP, hsCRP and IL-6. Both CI and ABSI were negatively correlated with HGS. In age-weighted survival analysis, higher CI and ABSI were associated with higher risk of CVE (Wald test = 4.92, p = 0.027; Wald test = 4.95, p = 0.026, respectively) and all-cause mortality (Wald test = 5.24, p = 0.022; Wald test = 5.19, p = 0.023, respectively). In RMST analysis, low vs. high and middle tertiles of CI and ABSI associated with prolonged CVE-free time and death-free time, and these differences between groups increased over time. Conclusion: Abdominal fat deposit indices, CI and ABSI, predicted CV outcomes and all-cause mortality, and were significantly associated with the inflammatory status in CKD patients.

Nutritional status and the risk of malnutrition in older adults with chronic kidney disease - implications for low protein intake and nutritional care: A critical review endorsed by ERN-ERA and ESPEN.

Increased life expectancy is posing unprecedented challenges to healthcare systems worldwide. These include a sharp increase in the prevalence of chronic kidney disease (CKD) and of impaired nutritional status with malnutrition-protein-energy wasting (PEW) that portends worse clinical outcomes, including reduced survival. In older adults with CKD, a nutritional dilemma occurs when indications from geriatric nutritional guidelines to maintain the protein intake above 1.0 g/kg/day to prevent malnutrition need to be adapted to the indications from nephrology guidelines, to reduce protein intake in order to prevent or slow CKD progression and improve metabolic abnormalities. To address these issues, the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Renal Nutrition group of the European Renal Association (ERN-ERA) have prepared this conjoint critical review paper, whose objective is to summarize key concepts related to prevention and treatment of both CKD progression and impaired nutritional status using dietary approaches, and to provide guidance on how to define optimal protein and energy intake in older adults with differing severity of CKD. Overall, the authors support careful assessment to identify the most urgent clinical challenge and the consequent treatment priority. The presence of malnutrition-protein-energy wasting (PEW) suggests the need to avoid or postpone protein restriction, particularly in the presence of stable kidney function and considering the patient's preferences and quality of life. CKD progression and advanced CKD stage support prioritization of protein restriction in the presence of a good nutritional status. Individual risk-benefit assessment and appropriate nutritional monitoring should guide the decision-making process. Higher awareness of the challenges of nutritional care in older adult patients with CKD is needed to improve care and outcomes. Research is advocated to support evidence-based recommendations, which we still lack for this increasingly large patient subgroup.

Muscle fat infiltration in chronic kidney disease: a marker related to muscle quality, muscle strength and sarcopenia.

Muscle fat infiltration (MFI) also known as myosteatosis refers to any deposit of lipids found in the skeletal muscle. MFI is preferably assessed by image-based methods like computed tomography (CT), magnetic resonance image (MRI) and ultrasound, normally from muscle groups located in the legs, arms and in the trunk. MFI is understood as a marker of muscle quality, where a muscle with higher fat deposition has lower contraction power and capacity to produce force per unit of muscle mass. This concept supports the hypothesis that a decrease in muscle strength is not always explained by a decrease in muscle mass, but also by other factors, including lipid deposition in the muscle. In the general population, MFI is associated with older age, physical inactivity and with insulin resistance and inflammation. In chronic kidney disease (CKD), MFI has been associated with a decrease in muscle strength and impaired muscle quality as well as with metabolic abnormalities, cardiovascular disease and increased mortality. Interventions aimed at reducing MFI in CKD are incipient, but it seems that guided exercise can ameliorate muscle quality in patients on hemodialysis. The aim of this narrative review about MFI in CKD is to draw attention to a still not often addressed complication in CKD. We conclude that more studies are warranted to investigate mechanisms and factors promoting MFI in CKD. Thus, clinical trials aimed at understanding the type, frequency and intensity of exercise that can diminish MFI and improve the clinical condition of the patients are needed.

Gut microbiota disturbances and protein-energy wasting in chronic kidney disease: a narrative review.

Protein-energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality, and lower quality of life. It is a complex syndrome, in which inflammation and retention of uremic toxins are two main factors. Causes of inflammation and uremic toxin retention in CKD are multiple; however, gut dysbiosis plays an important role, serving as a link between those entities and PEW. Besides, there are several pathways by which microbiota may influence PEW, e.g., through effects on appetite mediated by microbiota-derived proteins and hormonal changes, or by impacting skeletal muscle via a gut-muscle axis. Hence, microbiota disturbances may influence PEW independently of its relationship with local and systemic inflammation. A better understanding of the complex interrelationships between microbiota and the host may help to explain how changes in the gut affect distant organs and systems of the body and could potentially lead to the development of new strategies targeting the microbiota to improve nutrition and clinical outcomes in CKD patients. In this review, we describe possible interactions of gut microbiota with nutrient metabolism, energy balance, hunger/satiety signals and muscle depletion, all of which are strongly related to PEW in CKD patients.