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.

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.

The impact of muscle mass and myosteatosis on mortality in critically ill patients with Sars-Cov2-related pneumonia.

BACKGROUND & AIMS: Sars-Cov-2 pneumonia can lead to severe complications, requiring invasive mechanical ventilation and admission to the intensive care unit (ICU). Low muscle quantity and quality (the latter evaluated by the amount of ectopic fat infiltration in the muscle [myosteatosis]) at ICU admission are associated with worse outcomes in critically ill patients. The purpose of the present study is to assess muscle mass and myosteatosis of paravertebral skeletal muscle, in critically ill patients with Sars-Cov2 pneumonia and its association with mortality. METHODS: We conducted a retrospective observational study in 110 critically ill patients with severe Sars-Cov-2 pneumonia that had a high - resolution chest Computerized Tomography (HR-CT) at ICU admission. We acquired CT images at the level of the thoracic 12 (T12) vertebral body and measured skeletal muscle area (SMA), intermuscular adipose tissue (IMAT), and low attenuation muscle area (LAMA). Patients were followed until ICU mortality or discharge. RESULTS: Patients were 59.8 ± 8.1 years old, 77% were male. Seventy-nine percent of patients were considered at nutritional risk, and 22% were obese. Average Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 17 ± 5.4, and the overall ICU mortality was 48,2% (53/110). At ICU admission, both parameters of myosteatosis were associated with higher mortality (IMAT [per 10% increase] HR: 2.01 (95% Confidence Interval [CI] 1.27 to 3.17), P = 0.003; LAMA HR [per 10% increase]: 1.53 (95% CI 1.10 to 2.13), P = 0.012). CONCLUSION: Myosteatosis as assessed by CT scans plays a relevant role as a prognostic marker in critically ill patients with Sars-Cov2 severe pneumonia.

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.

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.

Simplified regional citrate anticoagulation protocol for CVVH, CVVHDF and SLED focused on the prevention of KRT-related hypophosphatemia while optimizing acid-base balance.

BACKGROUND: Hypophosphatemia is a common electrolyte disorder in critically ill patients undergoing prolonged kidney replacement therapy (KRT). We evaluated the efficacy and safety of a simplified regional citrate anticoagulation (RCA) protocol for continuous venovenous hemofiltration (CVVH), continuous venovenous hemodiafiltration (CVVHDF) and sustained low-efficiency dialysis filtration (SLED-f). We aimed at preventing KRT-related hypophosphatemia while optimizing acid-base equilibrium. METHODS: KRT was performed by the Prismax system (Baxter) and polyacrylonitrile AN69 filters (ST 150, 1.5 m2, Baxter), combining a 18 mmol/L pre-dilution citrate solution (Regiocit 18/0, Baxter) with a phosphate-containing solution (HPO42- 1.0 mmol/L, HCO3- 22.0 mmol/L; Biphozyl, Baxter). When needed, phosphate loss was replaced with sodium glycerophosphate pentahydrate (Glycophos™ 20 mmol/20 mL, Fresenius Kabi Norge AS, Halden, Norway). Serum citrate measurements were scheduled during each treatment. We analyzed data from three consecutive daily 8-h SLED-f sessions, as well as single 72-h CVVH or 72-h CVVHDF sessions. We used analysis of variance (ANOVA) for repeated measures to evaluate differences in variables means (i.e. serum phosphate, citrate). Because some patients received phosphate supplementation, we performed analysis of covariance (ANCOVA) for repeated measures modelling phosphate supplementation as a covariate. RESULTS: Forty-seven patients with acute kidney injury (AKI) or end stage kidney disease (ESKD) requiring KRT were included [11 CVVH, 11 CVVHDF and 25 SLED-f sessions; mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score 25 ± 7.0]. Interruptions for irreversible filter clotting were negligible. The overall incidence of hypophosphatemia (s-P levels <2.5 mg/dL) was 6.6%, and s-P levels were kept in the normality range irrespective of baseline values and the KRT modality. The acid-base balance was preserved, with no episode of citrate accumulation. CONCLUSIONS: Our data obtained with a new simplified RCA protocol suggest that it is effective and safe for CVVH, CVVHDF and SLED, allowing to prevent KRT-related hypophosphatemia and maintain the acid-base balance without citrate accumulation. TRIAL REGISTRATION: NCT03976440 (registered 6 June 2019).

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.

Survey on Carbapenem-Resistant Bacteria in Pigs at Slaughter and Comparison with Human Clinical Isolates in Italy.

This study is focused on resistance to carbapenems and third-generation cephalosporins in Gram-negative microorganisms isolated from swine, whose transmission to humans via pork consumption cannot be excluded. In addition, the common carriage of carbapenem-resistant (CR) bacteria between humans and pigs was evaluated. Sampling involved 300 faecal samples collected from slaughtered pigs and 300 urine samples collected from 187 hospitalised patients in Parma Province (Italy). In swine, MIC testing confirmed resistance to meropenem for isolates of Pseudomonas aeruginosa and Pseudomonas oryzihabitans and resistance to cefotaxime and ceftazidime for Escherichia coli, Ewingella americana, Enterobacter agglomerans, and Citrobacter freundii. For Acinetobacter lwoffii, Aeromonas hydrofila, Burkolderia cepacia, Corynebacterium indologenes, Flavobacterium odoratum, and Stenotrophomonas maltophilia, no EUCAST MIC breakpoints were available. However, ESBL genes (blaCTXM-1, blaCTX-M-2, blaTEM-1, and blaSHV) and AmpC genes (blaCIT, blaACC, and blaEBC) were found in 38 and 16 isolates, respectively. P. aeruginosa was the only CR species shared by pigs (4/300 pigs; 1.3%) and patients (2/187; 1.1%). P. aeruginosa ST938 carrying blaPAO and blaOXA396 was detected in one pig as well as an 83-year-old patient. Although no direct epidemiological link was demonstrable, SNP calling and cgMLST showed a genetic relationship of the isolates (86 SNPs and 661 allele difference), thus suggesting possible circulation of CR bacteria between swine and humans.

Quadriceps muscle thickness assessed by ultrasound is independently associated with mortality in hemodialysis patients.

BACKGROUND/OBJECTIVES: Estimation of muscle mass is an integral part of nutritional assessment in End-Stage Kidney Disease (ESKD) patients on chronic hemodialysis (HD). In this respect, muscle ultrasound (US) is a valid and reliable tool but has not been previously related to outcomes in this population. Aims of this study were to assess the relationship between quadriceps muscle thickness as assessed by US and outcomes in ESKD patients on HD; we also compared US with anthropometry and malnutrition inflammation score (MIS). SUBJECTS/METHODS: In this prospective study, 181 prevalent patients on HD were included. Thickness of the quadriceps rectus femoris and vastus intermedius (VIT) were assessed separately using ultrasonography, and were indexed for height squared. Mid-arm muscle circumference (MAMC) and area (MAMA) were assessed by anthropometry. MIS was evaluated. In the absence of predetermined cut-offs, values below the median of the distribution of VIT index were considered low. Instead, cut-off for anthropometric values such as MAMC and MAMA were set at ≥90% of agreement with the 50th percentile of the sex- and age-specific normal distribution. Cox-regression analysis was used to assess the association of US, MIS, and anthropometric parameters with mortality. RESULTS: Patients were followed for a median of 35 months. During this period 36% of patients died. Multivariable Cox-regression analysis (adjusted for demographic, biochemical and clinical variables), demonstrated that higher VIT distal index values were independently associated with lower mortality risk (HR: 0.76 (0.59-0.99); P = 0.040), whilst higher MIS values were independently associated with higher (HR 1.22 (1.10-1.35); P < 0.001) mortality risk. When assessing muscle parameters as categorical variables, both low VIT distal index (HR: 1.71 (1.01-2.89); 0.045) and MAMC (HR: 1.74 (1.02-2.96); 0.042) were independently associated with increased risk of death. CONCLUSION: Indexed distal VIT was independently associated with mortality both as continuous and as a categorical variable. Muscle US is a simple practical tool that adds prognostic information to the bedside nutritional assessment in ESKD patients on maintenance HD.

Fiber intake and health in people with chronic kidney disease.

Emerging evidence suggests that diet, particularly one that is rich in dietary fiber, may prevent the progression of chronic kidney disease (CKD) and its associated complications in people with established CKD. This narrative review summarizes the current evidence and discusses the opportunities for increasing fiber intake in people with CKD to improve health and reduce disease complications. A higher consumption of fiber exerts multiple health benefits, such as increasing stool output, promoting the growth of beneficial microbiota, improving the gut barrier and decreasing inflammation, as well decreasing uremic toxin production. Despite this, the majority of people with CKD consume less than the recommended dietary fiber intake, which may be due in part to the competing dietary potassium concern. Based on existing evidence, we see benefits from adopting a higher intake of fiber-rich food, and recommend cooperation with the dietitian to ensure an adequate diet plan. We also identify knowledge gaps for future research and suggest means to improve patient adherence to a high-fiber diet.

Low skeletal muscle mass by computerized tomography is associated with increased mortality risk in end-stage kidney disease patients on hemodialysis.

BACKGROUND AND AIMS: Skeletal muscle (SM) area, as measured by abdominal CT at the level of the third lumbar vertebra (L3), has been proposed as a proxy of whole body muscle mass. However, population-specific reference values are lacking. In the present study we aimed at: (1) detecting low SM area on abdominal CT images in patients on hemodialysis by applying cut-offs derived from a group of healthy subjects, and (2) estimating the independent risk of all-cause mortality associated with low SM area. METHODS: We retrospectively enrolled 212 adult patients on hemodialysis, undergoing abdominal CT scan (study group), and 87 healthy kidney donors (reference group). We obtained the gender-specific 5th percentile values of the abdominal SM area distribution from both the whole control group and the subgroup of younger (29-60 years) subjects, which we used as reference cut-offs. Then we applied those cut-offs in the study group to identify patients with low SM area. We used survival and Cox regression analysis to evaluate the risk of all-cause mortality associated with low abdominal SM area. RESULTS: In the fully adjusted Cox regression analysis, the patients with low abdominal SM area had a higher risk of death than the patients with values above the reference cut-off derived in the subgroup of younger controls (adjHR = 1.79 (1.21; 2.67), P = 0.004). CONCLUSIONS: Abdominal CT imaging can be used to detect low abdominal SM area in patients on hemodialysis by applying cut-offs derived from healthy subjects sharing a similar ethnic background. Low SM area as assessed by CT is independently associated with all-cause mortality in ESKD patients on hemodialysis.

A Comparative Analysis of Nutritional Assessment Using Global Leadership Initiative on Malnutrition Versus Subjective Global Assessment and Malnutrition Inflammation Score in Maintenance Hemodialysis Patients.

OBJECTIVE: Malnutrition is a prevalent condition in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the performance of the recently developed GLIM (Global Leadership Initiative on Malnutrition) in MHD by assessing the agreement, accuracy, sensitivity, specificity, and survival prediction of GLIM when compared to 7-point subjective global assessment (7p-SGA) and malnutrition inflammation score (MIS). DESIGN AND METHODS: We investigated 2 cohorts: MHDltaly (121 adults from Italy; 67 ± 16 years, 65% men, body mass index 25 ± 5 kg/m2) and MHDBrazil (169 elderly [age > 60 years] from Brazil; 71 ± 7 years, 66% men, body mass index 25 ± 4 kg/m2), followed for all-cause mortality for median 40 and 17 months, respectively. We applied the 2-step approach from GLIM: (1) screening and (2) confirming malnutrition by phenotypic and etiologic criteria. For 7p-SGA and MIS, a score ≤5 and ≥8, respectively, defined malnutrition. RESULTS: Malnutrition was present in 38.8% by GLIM, 25.6% by 7p-SGA, and 29.7% by MIS in the MHDItaly cohort, and in 47.9% by GLIM, 59.8% by 7p-SGA, and 49.7% by MIS in the MHDBrazil cohort. Cohen's kappa coefficient (κ) showed only "fair" agreement between GLIM and SGA (MHDItaly: κ = 0.26, P = .003; MHDBrazil: κ = 0.22, P = .003) and between GLIM and MIS (MHDItaly: κ = 0.33, P < .001; MHDBrazil: κ = 0.25, P = .001). Cox regression analysis showed that all 3 methods were able to predict mortality in crude analysis; however in the adjusted model, the association seemed more consistent and stronger in magnitude for 7p-SGA and MIS. CONCLUSION: In MHD patients, GLIM showed low agreement, sensitivity, and accuracy in identifying malnourished subjects by either 7p-SGA or MIS. Considering the specific wasting characteristics that predominate in MHD, the well-established 7p-SGA and MIS methods may be more useful in this clinical setting.