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Patients affected by chronic kidney disease (CKD) have an increased risk of developing cognitive impairment. The cause of mental health disorders in CKD and in chronic hemodialysis patients is multifactorial, due to the interaction of classical cardiovascular disease risk factors, kidney- and dialysis-related risk factors with depression, and multiple drugs overuse. A large number of compounds, defined as uremic toxins that normally are excreted by healthy kidneys, accumulate in the circulations, in the tissues, and in the organs of CKD patients. Among the candidate uremic toxins are several guanidino compounds, such as Guanidine. Uremic toxins may also accumulate in the brain and may have detrimental effects on cerebral resident cells (neurons, astrocytes, microglia) and microcirculation. The present study aims to analyze the effect of Guanidine on hippocampal excitatory postsynaptic field potentials (fEPSPs) and in CA1 pyramidal neurons recorded intracellularly. Moreover, we compared these effects with the alterations induced in vitro by CKD patients derived serum samples. Our results show an increased, dose-dependent, synaptic activity in the CA1 area in response to both synthetic Guanidine and patient’s serum, through a mechanism involving glutamatergic transmission. In particular, the concomitant increase of both NMDA and AMPA component of the excitatory postsynaptic currents (EPSCs) suggests a presynaptic mechanism. Interestingly, in presence of the lower dose of guanidine, we measure a significant reduction of EPSCs, in fact the compound does not inhibit GABA receptors allowing their inhibitory effect of glutamate release. These findings suggest that cognitive symptoms induced by the increase of uremic compounds in the serum of CKD patients are caused, at least in part, by an increased glutamatergic transmission in the hippocampus.

Background: The factors associated with the inability to start hemodialysis with an arteriovenous fistula (AVF) in chronic kidney disease patients are not fully understood. Aim: Evaluating factors associated with type of vascular access at the first chronic hemodialysis and at 1 year after it. Methods: The study cohort includes patients registered in the Regional Dialysis and Transplant Registry of Lazio undergoing first hemodialysis between 2008 and 2015. Logistic regression models were used to evaluate the association between socio-demographic, clinical and care/organizational factors, and vascular access at first hemodialysis. Cox regression models were used to assess the odds of switching to AVF during the first year of hemodialysis among patients starting dialysis with central venous catheter (CVC). Results: In the cohort of 6208 incident hemodialysis patients, 52.7% had an AVF and 47.3% had a CVC. Among the 2939 incident patients with CVC, 27.4% switched to FAV after 1 year. A higher probability of starting dialysis with AVF was observed among males (OR = 1.83; 95% CI 1.63–2.06), while a lower probability was observed among patients aged >85 years (OR 0.64; IC 95% 0.51–0.80). Patients with early referral to a nephrologist had a triple probability of start dialysis with AVF. We observed a higher odds of switch to AVF among males (HR = 1.62; 95% CI 1.40–1.89) and a lower odds among patients over 65 years. Conclusion: The observed high rate of AVF at the start of hemodialysis and of the switch from CVC to AVF in the first year, although declining since 2008, is a positive outcome. However, over one-third of patients maintain the CVC as vascular access for the first year because of unmodifiable factors, such as gender, age, comorbidity. The present study suggests that logistics/management and assistance/welfare problems may contribute to the delay or lack of AVF placement in incident hemodialysis patients or within the first year of dialysis.

Background Fatigue in haemodialysis (HD) patients is a prevalent but complex symptom impacted by biological, behavioural, psychological and social variables. Conventional retrospective fatigue questionnaires cannot provide detailed insights into symptom variability in daily life and related factors. The experience sampling methodology (ESM) overcomes these limitations through repeated momentary assessments in patients’ natural environments using digital questionnaires. This study aimed to gain in-depth understanding of HD patients’ diurnal fatigue patterns and related variables using a mobile Health (mHealth) ESM application and sought to better understand the nature of their interrelationships. Methods Forty HD patients used the mHealth ESM application for 7 days to assess momentary fatigue and potentially related variables, including daily activities, self-reported physical activity, social company, location and mood. Results Multilevel regression analyses of momentary observations (n = 1777) revealed that fatigue varied between and within individuals. Fatigue was significantly related to HD treatment days, type of daily activity, mood and sleep quality. Time-lagged analyses showed that HD predicted higher fatigue scores at a later time point (β = 0.22, P = 0.013). Interestingly, higher momentary fatigue also significantly predicted more depressed feelings at a later time point (β = 0.05, P = 0.019) but not the other way around. Conclusions ESM offers novel insights into fatigue in chronic HD patients by capturing informative symptom variability in the flow of daily life. Electronic ESM as a clinical application may help us better understand fatigue in HD patients by providing personalized information about its course and relationship with other variables in daily life, paving the way towards personalized interventions.

Dopaminergic nigrostriatal denervation and widespread intracellular α-synuclein accumulation are neuropathologic hallmarks of Parkinson’s disease (PD). A constellation of peripheral processes, including metabolic and inflammatory changes, are thought to contribute to neurodegeneration. In the present study, we sought to obtain insight into the multifaceted pathophysiology of PD through the application of a multi-marker discovery approach. Fifty older adults aged 70+, 20 with PD and 30 age-matched controls were enrolled as part of the EXosomes in PArkiNson Disease (EXPAND) study. A panel of 68 circulating mediators of inflammation, neurogenesis and neural plasticity, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel), a multi-platform regression method developed to handle highly correlated variables organized in multi-block datasets. The SO-CovSel model with the best prediction ability using the smallest number of variables was built with seven biomolecules. The model allowed correct classification of 94.2 ± 3.1% participants with PD and 100% controls. The biomarker profile of older adults with PD was defined by higher circulating levels of interleukin (IL) 8, macrophage inflammatory protein (MIP)-1β, phosphoethanolamine, and proline, and by lower concentrations of citrulline, IL9, and MIP-1α. Our innovative approach allowed identifying and evaluating the classification performance of a set of potential biomarkers for PD in older adults. Future studies are warranted to establish whether these biomolecules could serve as biomarkers for PD as well as unveil new targets for interventions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11357-020-00192-2) contains supplementary material, which is available to authorized users.

Whether hemodiafiltration (HDF) is better than conventional hemodialysis (HD) in improving left ventricular hypertrophy (LVH), defined as reduction of the left ventricular mass index (LVMi) and increasing the ejection fraction (EF), is unclear. A systematic literature search was performed. Primary outcome was the mean difference between pre- and post-procedural LVMi. Secondary outcome was the mean difference in EF. Seven studies with a total of 845 patients were included. The pooled mean difference between pre-and post-procedural LVMi was -8.0 g/m2 (95% confidence interval [CI] -13.1, -2.8). On subgroup analysis, the mean differences between pre- and post-procedural LVMi for HD and HDF were -6.7 g/m2 (95% CI -14.5, 1.1) and -9.3 g/m2 (95% CI -16.3, -2.3), respectively (P for subgroups = .62). Pooled mean difference between pre- and post-procedural EF was 2.4% (95% CI -1.8, 6.5). On subgroup analysis, the mean differences between pre- and post-procedural EF for HD and HDF were 3.6% (95% CI -2.7, 9.8) and 2.0% (95% CI 2.9, 6.8), respectively (P for subgroups = .68). On meta-regression, age (Beta -0.35 ± 0.05, P

Thirst has been defined as "the sensation that leads animal's and human's actions toward the goal of finding and drinking water" or as "any drive that can motivate water intake, regardless of cause". Thirst, together with xerostomia, is the main cause of poor adherence to fluid restriction and of excessive intake of fluids in patients on chronic hemodialysis, and consequently of high interdialytic weight gain. Interdialytic weight gain (IDWG) should be lower than 4.0-4.5% of dry weight. Unfortunately, many patients have an IDWG greater than this value and some have IDWG of 10-20%. High IDWG is associated with a higher risk of all-cause and cardiovascular death and increased morbidity, such as ventricular hypertrophy and major adverse cardiac and cerebrovascular events. In addition, high IDWG leads to supplementary weekly dialysis sessions with consequent deterioration of quality of life and increased costs. Thus, the knowledge of thirst in patients on chronic hemodialysis is essential to prompt its adequate management to limit IDWG in the routine clinical practice. The present review aims to describe the physiology of thirst in patients on chronic hemodialysis, as well as the prevalence, its measures, the associated variables, the consequences, and the strategies for its reduction.

Background Although frequent and debilitating, little is known about the characteristics of post-dialysis fatigue (PDF). Objective To characterise the intensity, duration and frequency of PDF and the associated variables in patients on chronic haemodialyses. Design Prospective, observational and multicenter study. Patients We studied 271 patients. Measurements Patients were considered to be suffering from PDF if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis? Then, each patient was invited to rate the intensity, duration and frequency of PDF from 1 to 5. Results One hundred sixty-four patients (60.5%) had PDF. The median [95% confidence interval (CI)] scores of PDF intensity, duration and frequency were 3 (3-4), 3 (3-4) and 4 (4-4), respectively. The median (95% CI) of the sum of the scores (Sum Score) of PDF intensity, duration and frequency was 11 (10-12). Seventy four patients had a Sum Score ≥ 12. Using multiple regression analysis, PDF intensity was associated with dialytic age and ultrafiltration rate (UFR), PDF duration with dialytic age, while PDF fatigue frequency was associated with height. The Sum Score was associated with dialytic age and recovery time and negatively associated with daily activity, height and UFR (ml/kg/h). Conclusion The intensity, duration and frequency of PDF are high in a large percentage of patients, suggesting that PDF is an intense event in terms of quantity and quality. Understanding the relationship between the variables associated with PDF and its intensity, duration and frequency may help better understand the underlying mechanisms of this burdensome condition.

Fatigue is a commonly reported and debilitating symptom among patients with CKD, yet little is known about its epidemiology, pathogenesis, and treatment. Various measurement tools have been used in published studies to identify and quantify fatigue. These include several single-item measures embedded in longer questionnaires for assessing depression, quality of life, or symptom burden in patients with kidney disease. Approximately 70% of patients with CKD report fatigue, with up to 25% reporting severe symptoms. Patient-reported fatigue is associated with death, dialysis initiation, and hospitalization among individuals with CKD. The pathophysiology is multifactorial and likely includes decreased oxygen delivery and increased reliance on anaerobic metabolism, thus generating lactic acidosis in response to exertion; the effects of chronic metabolic acidosis and hyperphosphatemia on skeletal muscle myocytes; protein-energy wasting and sarcopenia; and depression. Physical activity has been shown to improve fatigue in some small but promising trials, and so should be recommended, given the additional benefits of exercise. Targeting higher hemoglobin levels with erythropoiesis-stimulating agents may improve fatigue, but potential adverse cardiovascular effects preclude their use to solely treat fatigue without the presence of another indication. Current guidelines recommend cautious individualization of hemoglobin targets for those at low cardiovascular risk who still experience fatigue or functional limitation despite a hemoglobin level of 10 g/dl. Sodium bicarbonate supplementation for the treatment of metabolic acidosis may also improve functional status. Selective serotonin reuptake inhibitors have not been consistently shown to improve fatigue in patients with kidney disease, but an ongoing trial will evaluate the effect of alternative antidepressant drug and behavioral activation therapy on fatigue in patients with CKD. Overall, more research is needed to further clarify underlying mechanisms of fatigue and identify effective, targeted treatments for patients with CKD.

Recently, it has been demonstrated that chronic inflammation could have a role on fatigue onset in chronic hemodialysis (HD). Research on neuro-immune interactions highlighted that an alteration of basal ganglia functioning, secondary to chronic inflammation, may translate in a reduced motivation and altered reward processes in chronic diseases. This study investigated a possible correlation between fatigue severity and reward mechanisms, that regulate motivational dispositions, in HD patients. Evaluation scales were administered to ninety-four patients on HD (54 Male, 40 Female; Md

Fatigue is still present in up to 40–50% of kidney transplant recipients (KTR), the results of studies comparing the prevalence among patients on hemodialysis (HD) and KTR led to conflicting results. Fatigue correlates include inflammation, symptoms of depression, sleep disorders and obesity. Fatigue in KTR leads to significant functional impairment, it is common among KTR poorly adherent to immunosuppressive therapy and is associated with a serious deterioration of quality of life. The following databases were searched for relevant studies up to November 2020: Medline, PubMed, Web of Science and the Cochrane Library. Several studies have compared the prevalence and severity of fatigue between KTR and hemodialysis or healthy patients. They have shown that fatigue determines a significant functional deterioration with less chance of having a paid job and a significant change in quality of life. The aim of the review is to report methods to assess fatigue and its prevalence in KTR patients, compared to HD subjects and define the effects of fatigue on health status and daily life. There is no evidence of studies on the treatment of this symptom in KTR. Efforts to identify and treat fatigue should be a priority to improve the quality of life of KTR.

(1) Background: Interest in gender disparities in epidemiology, clinical features, prognosis and health care in chronic kidney disease patients is increasing. Aims of the study were to evaluate the association between gender and vascular access (arteriovenous fistula (AVF) or central venous catheter (CVC)) used at the start of hemodialysis (HD) and to investigate the association between gender and 1-year mortality. (2) Methods: The study includes 9068 adult chronic HD patients (64.7% males) registered in the Lazio Regional Dialysis Register (Jan 2008–Dec 2018). Multivariable logistic regression models were used to investigate the associations between gender and type of vascular access (AVF vs. CVC) and between gender and 1-year mortality. Interactions between gender and socio-demographic and clinical variables were tested adding the interaction terms in the final model. (3) Results: Females were older, had lower educational level and lower rate of self-sufficiency compared to males. Overall, CVC was used in 51.2% of patients. Females were less likely to use AVF for HD initiation than males. 1354 out of 8215 (16.5%) individuals died at the end of the follow-up period. Interaction term between gender and vascular access was significant in the adjusted model. From stratified analyses by vascular access, OR female vs. male (AVF) = 0.65, 95% CI 0.48–0.87 and OR female vs. male (CVC) = 0.88, 95% CI 0.75–1.04 were found. (4) Conclusion: This prospective population-based cohort study in a large Italian Region showed that in females starting chronic HD AVF was less common respect to men. The better 1-year survival of females is more evident among those women with AVF. Reducing gender disparity in access to AVF represents a key point in the management of HD patients.

Background and Aims Fatigue is one of the most prioritized outcomes among haemodialyis (HD) patients with great impact on health-related quality of life. However, evidence-based therapies are lacking. A better understanding of fatigue symptoms and related behavioral, social and psychological factors in HD patients is of primary importance. Conventionally used fatigue measurement instruments, such as the Fatigue Severity Scale (FSS), only provide a general picture of fatigue severity and are prone to memory bias due to their retrospective nature. However, they cannot provide detailed insight in diurnal variations in fatigue and related factors in daily life. The Experience Sampling Methodology (ESM) overcomes these limitations by repeated “real-time” assessments in patients’ natural environments using digital questionnaires. The aims of this study were (i) to gain in-depth understanding of HD patients’ diurnal fatigue patterns and related variables using a mobile Health (mHealth) ESM application, (ii) to better understand the nature of their interrelationships, and (iii) to explore the relationship between real-time experience of fatigue and its retrospective assessment. Method Forty chronic HD patients used the mHealth ESM application for seven consecutive days to assess momentary fatigue and potentially related variables, including daily activities, self-reported physical activity, social company, location and mood patterns. In addition, patients retrospectively evaluated their fatigue experience over the preceding day and week by means of end-of-day, and end-of-week questionnaires and the FSS. Results Multilevel regression analyses of momentary observations (N=1778) revealed that fatigue varied between and within individuals (Fig.1). Fatigue was significantly related to type of daily activity and mood. Time-lagged analyses showed that HD treatment predicted higher fatigue scores at a later time point, β = 0.22, p = 0.013. Interestingly, higher momentary fatigue also significantly predicted more depressed feelings at a later time point, β = 0.05, p = 0.019, but not the other way around. Retrospective evaluation of fatigue experience over the preceding week was significantly higher than the average of momentary fatigue scores, t(38) = 3.54, p = 0.001. The FSS correlated moderately with the average of momentary fatigue scores, r = 0.63. Conclusion This study demonstrates diurnal variability of fatigue in chronic HD patients. It also corroborates a previous result from our research group showing that fatigue increases as a response to HD treatment (i.e. post-dialysis fatigue) and should, at least partially, be distinguished from a more general fatigue experience. Furthermore, our findings may suggest that depressed mood is secondary to fatigue in HD patients given their temporal relationship. Finally, retrospective fatigue assessment led to overestimation of the real-time fatigue experience. ESM offers novel insights in fatigue in HD patients by capturing informative symptom variability in the flow of daily life, which is not provided by conventional fatigue measures. Moreover, ESM provides personalized information about fatigue symptoms and their relationship with other variables in daily life, paving the way towards personalized interventions for HD patients.

Background: The aetiology of postdialysis fatigue (PDF), an intermittent but debilitating fatigue occurring after haemodialysis (HD) treatment, is still unclear. In other inflammatory diseases, increasing evidence points toward the involvement of the immune system in the onset of fatigue symptoms. Altered serum levels of inflammatory cytokines have also been shown in HD patients. Therefore, we investigated whether pre- and postdialysis serum levels of pro- and anti-inflammatory cytokines (i.e. IL-1β, IL-6, TNF-α and IL-10) or their intradialytic changes (if any) were related to PDF or the time HD patients reported needing to recover from HD treatment (TIRD). Methods: Serum levels of IL-1β, IL-6, TNF-α and IL-10 were measured immediately before and after HD in 45 patients using commercially available kits on an ELLA™ automated immunoassay system. The presence and severity of PDF as well as TIRD duration were assessed by self-report measures. Key results: Seventy-four percent of patients reported PDF, with a median PDF severity index of 3.30 [IQR: 3.00–4.30] on a scale from 1 to 5. Median TIRD was 120 min [IQR: 60–480]. PDF severity correlated strongly with TIRD, rs = 0.85, p < 0.001. Only predialysis levels of IL-10 significantly and positively correlated with PDF severity (rs = 0.43, p = 0.003). Conclusion: Findings of the present study do not support the involvement of the immune system in the onset of PDF or the time patients needed to recover from HD treatment. A positive, but counterintuitive relationship was found between predialysis levels of anti-inflammatory IL-10 and PDF severity, which warrants further research.

Context Poor quality of life is a major problem in hemodialysis patients. Objectives This study was conducted to assess the effect of aromatherapy massage on hemodialysis patients' quality of life. Methods In this parallel randomized clinical trial study, 105 hemodialysis patients who meet the inclusion criteria were assessed and assigned into intervention and control groups using block randomization. Participants in the intervention groups received aromatherapy massage with Lavender essential oil or Citrus Aurantium essential oil for four weeks (three times per week). For the control group, only foot massage was performed. The level of quality of life was measured by the 36-Item Short-Form Health Survey questionnaire (SF-36) before and after the intervention. Data analysis was performed using descriptive and inferential statistics (analysis of variance, chi-square, and Fisher's exact tests). Results There was a significant difference between the mean score of quality of life in the Lavender essential oil group and Citrus Aurantium essential oil group with the control group after intervention. However, there was no significant difference between the mean score of quality of life in the Lavender essential oil group and Citrus Aurantium essential oil group after the intervention. Conclusions In this study, both aromatherapy massages have positive effects on the quality of life of hemodialysis patients. Therefore, nurses are advised to use these aromatherapy massages to improve the quality of life of hemodialysis patients.

Context Fatigue is prevalent among hemodialysis (HD) patients and associated with depressive mood. To advance our understanding of its etiology and develop appropriate treatments, reliable measurement instruments are needed. However, conventional fatigue and mood questionnaires are prone to bias because of their retrospective nature and may misrepresent or overestimate actual symptom experience (i.e., the so-called memory-experience gap). Experience sampling methodology (ESM) overcomes this limitation through repeated real-time assessments in patients' natural environment, thereby providing reliable and ecologically valid data. Objectives We investigated to what extent retrospective symptom reporting accurately represents real-time experiences of fatigue and mood in HD patients using an ESM mobile Health application (PsyMate™; smartHealth GmbH, Luxembourg). Methods Forty HD patients used the PsyMate for one week to assess real-time fatigue and mood. In addition, they retrospectively evaluated their symptom experience completing end-of-day and end-of-week questionnaires as well as the conventional Fatigue Severity Scale and Hospital Anxiety and Depression Scale. Results Results of real-time observations (N = 1777) showed that fatigue and mood varied between and within individuals. Retrospective end-of-week fatigue evaluation was significantly higher than the average real-time fatigue score; t(38) = 3.54, P = 0.001, and d = 0.57. Fatigue Severity Scale and Hospital Anxiety and Depression Scale correlated moderately to strong with the average ESM score for fatigue and mood: r = 0.66 and r = 0.77, respectively. Conclusion Retrospective fatigue assessment may lead to overestimation of real-time symptom experience. ESM provides detailed insight and personalized information about symptom experiences, which may be crucial for the design of more targeted and personalized interventions for fatigue and mood problems in HD patients.

Objective: Fatigue and depressed mood are considered main impediments to physical activity in haemodialysis (HD) patients. A better understanding of their interrelationships is crucial to develop effective therapies. Moreover, measurement of daily physical activity (DPA) in HD patients is tricky, as it is usually assessed by subjective self-report questionnaires. Therefore, we aimed to objectively measure sponteanous DPA with motion sensors and to explore its relation with fatigue and depressive symptoms. Methods: DPA was assessed for seven consecutive days in 37 HD patients based on their daily step count measured with the SenseWear™ Armband. The Fatigue Severity Scale (FSS) and Beck Depression Inventory-II (BDI-II) were administered to evaluate fatigue and depressed mood. Results: Median DPA was 2424 steps/day, (IQR:892–4545). In 81% of subjects, DPA felt within a sedentary lifestyle classification, as they made 13) (p = 0.111, d = 0.60), depressive mood did also not correlate significantly with DPA (rs = − 0.23, p = 0.175). Conclusion: Objective assessment of DPA with motion sensors is feasible in HD patients and allows identifying a sedentary lifestyle. Our results suggest that spontanous DPA is determined by age rather than by fatigue or mood.

BACKGROUND It is still unknown whether ERAS program is safe, feasible and effective in elderly patients undergoing laparoscopic colorectal surgery. In addition, the definition of the "old patient" in terms of age varies across the studies and different age cut-off, such as 65, 70, and 75 years have been used worldwide. METHODS All adult patients undergoing primary, elective colorectal laparoscopic surgery between January 2017 and December 2018 were considered eligible to follow the ERAS protocol according to the Enhanced Recovery After Surgery (ERAS) Society guidelines. Elderly were defined according three different cut-off values

Physical frailty and sarcopenia (PF&S) is a prototypical geriatric condition characterized by reduced physical function and low muscle mass. The aim of the present study was to provide an initial selection of biomarkers for PF&S using a novel multivariate analytic strategy. Two-hundred community-dwellers, 100 with PF&S and 100 non-physically frail, non-sarcopenic (nonPF&S) controls aged 70 and older were enrolled as part of the BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons (BIOSPHERE) study. A panel of 74 serum analytes involved in inflammation, muscle growth and remodeling, neuromuscular junction damage, and amino acid metabolism was assayed. Biomarker selection was accomplished through sequential and orthogonalized covariance selection (SO-CovSel) analysis. Separate SO-CovSel models were constructed for the whole study population and for the two genders. The model with the best prediction ability obtained with the smallest number of variables was built using seven biomolecules. This model allowed correct classification of 80.6 ± 5.3% PF&S participants and 79.9 ± 5.1% nonPF&S controls. The PF&S biomarker profile was characterized by higher serum levels of asparagine, aspartic acid, and citrulline. Higher serum concentrations of platelet-derived growth factor BB, heat shock protein 72 (Hsp72), myeloperoxidase, and α-aminobutyric acid defined the profile of nonPF&S participants. Gender-specific SO-CovSel models identified a “core” biomarker profile of PF&S, characterized by higher serum levels of aspartic acid and Hsp72 and lower concentrations of macrophage inflammatory protein 1β, with peculiar signatures in men and women. SO-CovSel analysis allowed identifying a set of potential biomarkers for PF&S. The adoption of such an innovative multivariate approach could help address the complex pathophysiology of PF&S, translate biomarker discovery from bench to bedside, and unveil novel targets for interventions.

Mitochondria are intracellular organelles involved in a myriad of activities. To safeguard their vital functions, mitochondrial quality control (MQC) systems are in place to support organelle plasticity as well as physical and functional connections with other cellular compartments. In particular, mitochondrial interactions with the endosomal compartment support the shuttle of ions and metabolites across organelles, while those with lysosomes ensure the recycling of obsolete materials. The extrusion of mitochondrial components via the generation and release of mitochondrial-derived vesicles (MDVs) has recently been described. MDV trafficking is now included among MQC pathways, possibly operating via mitochondrial–lysosomal contacts. Since mitochondrial dysfunction is acknowledged as a hallmark of aging and a major pathogenic factor of multiple age-associated conditions, the analysis of MDVs and, more generally, of extracellular vesicles (EVs) is recognized as a valuable research tool. The dissection of EV trafficking may help unravel new pathophysiological pathways of aging and diseases as well as novel biomarkers to be used in research and clinical settings. Here, we discuss (1) MQC pathways with a focus on mitophagy and MDV generation; (2) changes of MQC pathways during aging and their contribution to inflamm-aging and progeroid conditions; and (3) the relevance of MQC failure to several disorders, including neurodegenerative conditions (i.e., Parkinson’s disease, Alzheimer’s disease) and cardiovascular disease.

Sarcopenia, the progressive and generalised loss of muscle mass and strength/function, is a major health issue in older adults given its high prevalence and burdensome clinical implications. Over the years, this condition has been endorsed as a marker for discriminating biological from chronological age. However, the absence of a unified operational definition has hampered its full appreciation by healthcare providers, researchers and policy-makers. In addition to this unsolved debate, the complexity of musculoskeletal ageing represents a major challenge to the identification of clinically meaningful biomarkers. Here, we illustrate the advantages of biomarker discovery procedures in muscle ageing based on multivariate methodologies as an alternative approach to traditional single-marker strategies. The rationale, design and methods of the "BIOmarkers associated with Sarcopenia and PHysical frailty in EldeRly pErsons" (BIOSPHERE) study are described as an application of a multi-marker strategy for the development of biomarkers for the newly operationalised Physical Frailty & Sarcopenia condition.

The aim of the present study was to determine the intensity, duration, frequency and prevalence of postdialysis fatigue (PDF) in patients on chronic hemodialysis (PCD) with and without functional disability. Patients underwent assessment of functional ability by the Katz ADL (activity daily living) questionnaire and the Lawton and Brody scale for the instrumental activity daily living (IADL) fatigue using the SF-36 Vitality Subscale, comorbidity through the Charlson comorbidity score index (CDI), and time of recovery after hemodialysis (TIRD). We studied 271 PCD. ADL and IADL disabilities were present in 75 (27.6%) and 168 (62%) patients, respectively. Patients with ADL disability were significantly older and showed higher CDI scores, and lower levels of serum albumin and Kt/V. Prevalence of PDF was significantly higher in patients with ADL disability as well as its severity, intensity, duration and frequency. Patients with IADL disability were significantly older, had a higher CCI score, had lower levels of serum albumin and Kt/V, and had a higher severity, intensity, duration and frequency of PDF. At multivariate regression analysis, ADL disability was positively associated with age, prevalence and severity of PDF, and dialysate temperature and inversely associated with serum albumin levels. IADL disability was instead positively associated with age and dialysate temperature and inversely associated with serum albumin levels. In conclusion, prevalence and severity of PDF are significantly higher in PCD with ADL disability than in those without it. This knowledge may have important implications for the development of interventions to reduce PDF in PCD.

Aim The study aims to determine prevalence and severity of PDF and to define its associated variables. Methods In five haemodialysis units of northern-centre Italy, patients were regarded to suffer from PDF if they spontaneously offered this complaint when asked the open-ended question: Do you feel better or worse after dialysis? If worse, please specify in which way. A complaint of fatigue would be probed further with questions directed at its duration, frequency and intensity, allowing creation of a fatigue index of severity (one third of the sum of these three parameters, each rated from 1 to 5). Patients were stratified into three groups according the severity of PDF: 1) score = 0; 2) score = 1-3; 3) score > 3. Results We studied 271 patients: 164 had PDF and 107 did not. PDF patients had significantly longer time of recovery after dialysis (TIRD). TIRD was significantly associated with PDF duration, intensity, and frequency. Patients with PDF were older and had a lower ADL score. At multivariate analysis, PDF was significantly associated with TIRD. In a multivariate model that did not include TIRD, PDF was independently associated with age and ADL. Sixty patients had moderate PDF and 104 had severe PDF. In patients with severe PDF, age and dialytic age were higher, ADL and IADL scores were lower, TIRD was longer and the ultrafiltration rate was lower. At multivariate analysis, PDF severity was independently associated with TIRD. In the model without TIRD, PDF severity was associated with ADL only. Conclusion Post-dialysis fatigue is frequent and associated with age and ADL. Dialytic variables seem unrelated to PDF.

Health-related quality of life (HRQOL) in patients on chronic hemodialysis has not improved significantly in the last 20 years. This is largely due to their substantial symptom burden which is rarely assessed and treated in routine clinical practice. This is also consequence of the lack of an appropriate armamentarium for the treatments of such symptoms. Adequate studies on the causes and pathogenesis of the symptoms of hemodialysis patients are needed followed by high-quality studies on possible therapeutic pharmacological and non-pharmacological interventions. Patients on chronic hemodialysis deserve a better quality of life.

The goal of the pharmacological therapy in secondary hyperparathyroidism (SHPT) is to reduce serum levels of parathyroid hormone and phosphorus, to correct those of calcium and vitamin D, to arrest or reverse the parathyroid hyperplasia. However, when nodular hyperplasia or an autonomous adenoma develops, surgery may be indicated. We reviewed the literature with the aim of defining if the echographic criteria predictive of unresponsiveness of SHPT to calcitriol therapy are valid also in the cinacalcet era and if drug therapy may reverse nodular hyperplasia of parathyroid gland (PTG). The responsiveness to therapy and regression of the nodular hyperplasia of PTG remains an open question in the calcimimetic era as well as the cutoff between medical and surgical therapy. Prospective studies are needed in order to clarify if an earlier use of cinacalcet in moderate SHPT might arrest the progression of parathyroid growth and stabilize SHPT.

Fatigue is common in end-stage renal disease patients receiving hemodialysis, reduces significantly their quality of life and is associated with all-cause and cardiac-related mortality. Unfortunately, little is known about the course of fatigue in patients on chronic hemodialysis. The Vitality Subscale of the SF-36 (SF-36 VS), Short-Form Health Survey, was administered to 45 patients in January (T1), June (T2) and November (T3) 2015. The score of the SF-36 VS did not differ significantly among T1, T2 and T3. Similarly, the 1-year course of the SF-36 Vitality Subscale score did not differ significantly among T1, T2 and T3 after stratification of patients for sex, age, BMI, IADL and Charlson. Between T1 and T2, 21 out of 45 patients (46.6%) changed their fatigue status: 8 fatigued patients became not-fatigued and 13 not-fatigued patients became fatigued. Between T2 and T3, 12 out of 45 (26.6%) patients changed their fatigue status: 5 fatigued patients became not-fatigued and 7 not-fatigued patients became fatigued. Between T1 and T3, 19 out of 45 patients (42.2%) changed their fatigue status: 6 fatigued patients became not-fatigued and 13 not-fatigued became fatigued. The present study is the first to identify variations in fatigue status among patients on chronic hemodialysis during 1-year course. These findings suggest to frequently assess the presence and severity of fatigue in patients on chronic hemodialysis.

Background Little is known about the underlying aetiology of fatigue in haemodialysis (HD) patients apart from a significant association and overlapping symptomatology with depressive symptoms. Growing evidence exists for the involvement of the immune system, by pro-inflammatory cytokines, in the development of fatigue in other inflammatory diseases. In HD patients, increased exposure to bacterial endotoxins may contribute to an inflammatory response and may potentially lead to fatigue. We therefore aimed (i) to assess the interrelationship between serum endotoxin (EA) levels, interleukin-6 (IL-6) levels and fatigue in HD patients; (ii) to evaluate whether there is a relationship between depressive symptoms and inflammation as well and (iii) to what extent depressive symptoms and fatigue are related to each other. Methods Fatigue and depressive symptoms in daily life were assessed in 59 individuals using the SF-36 vitality subscale and the Geriatric Depression Scale. Blood samples were collected on a mid-week dialysis session to determine EA levels, through the Endotoxin Activity Assay (EAA™), and IL-6 concentrations, through the commercially available Abcam ELISA (Enzyme-Linked Immunosorbent Assay) kit. Results EA, IL-6 levels and depressive symptoms were significantly correlated with fatigue. EA levels and depressive symptoms were significant predictors of fatigue, explaining 31% of its variance. However, EA and IL-6 were not significantly associated with depression. Conclusions Fatigue in HD patients may be related to endotoxemia and inflammation through IL-6. Furthermore, fatigue is significantly associated with depressive symptoms. Future research into the causal interrelationship of inflammation, fatigue and depression in HD patients might lead to potential targets for therapeutic strategies.

Background The construct of physical frailty and sarcopenia (PF&S) identifies an age-related pre-disability condition defined by reduced physical performance and low muscle mass. Whether PF&S is characterized by perturbations of the cytokine network is presently unclear. Furthermore, the existence of gender-specific inflammatory profiles of PF&S is unknown. This study was designed to explore the association between a large panel of inflammatory biomolecules and PF&S in older adults through a multivariate statistical approach. Gender-specific inflammatory patterns were also explored. Methods One-hundred community-dwellers aged 70 years and older with PF&S and 100 non-sarcopenic, non-frail controls (nonPF&S) were enrolled. A panel of 30 circulating inflammatory biomarkers was assayed. Partial least squares discriminant analysis (PLS-DA) was employed to explore the relationship between inflammatory molecules and PF&S. Separate PLS-DA models were built for the whole sample and the two genders. Double cross-validation procedures were used to validate the predictive ability of PLS-DA models. Results The optimal complexity of the PLS-DA model built on the whole sample was found to be four latent variables. The proportion of correct classification was 75.6 ± 1.3% (82.3 ± 1.6% for enrollees with PF&S and 68.7 ± 2.5% for nonPF&S controls). The inflammatory profile of people with PF&S was defined by higher levels of P-selectin, C-reactive protein (CRP), and interferon γ-induced protein 10. NonPF&S participants were characterized by higher levels of myeloperoxidase (MPO), interleukin (IL) 8, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1-α, platelet-derived growth factor (PDGF) BB. Gender-specific PLS-DA allowed identifying a “core” inflammatory signature of PF&S, composed by higher levels of CRP, and lower concentrations of MPO, IL8, MCP-1, and PDGF-BB, with peculiar patterns of relationships for men and women. Conclusions A core inflammatory profile was identified in people with PF&S with a gender-specific signature. The dissection of the PF&S “cytokinome” will provide novel insights into the role played by inflammation in the disabling cascade and allow designing personalized treatment strategies.

Introduction: The present study aimed to determine the variables that are associated with a longer dialysis recovery time (DRT) and to define the relationship that exists between DRT and the ultrafiltration rate (UFR) in prevalent chronic hemodialysis (CHD) patients. Methods: We studied 210 prevalent CHD of 5 hemodialysis units in Central Italy. Patients were invited to answer to the question: “How long does it take you to recover from a dialysis session?” Answers to this question were subsequently converted into minutes. Demographic, clinical and laboratory parameters were recorded for each patient as well as the UFR (mL/kg/h), the dialysate sodium concentration and temperature. Results: Median DRT was 180 min (60–420). Ninety five (45%) patients had a DRT ≥ the median value. Mean UFR was 9.2 ± 3.0 mL/kg/h. Patients with a lower DRT had a less prevalent disability in the instrumental activities daily living, had a higher UFR, and a lower dialysate temperature, as compared with subjects with higher DRT. According to the logistic regression model, UFR was associated with a DRT below the median (i.e., 180) in the unadjusted model (OR 1.12; 95% CI 1.02–1.23; p = 0.019), after adjusting for age and sex (OR 1.11; 95% CI 1.01–1.22; p = 0.025), and in the fully adjusted model (OR 1.11; 95% CI 1.04–1.22; p = 0.040). UFR increase was associated with increasing probability of DRT below the median (p for trend = 0.035). The highest tertile of DRT was associated with UFR below the mean value (i.e., 9.2 mL/kg/h) in multinomial logistic regression having the lowest DRT tertile as reference. DRT was significantly lower in patients with UFR > 13 mL/kg/h than in patients with UFR 10–13 or < 10 mL/kg/h. Conclusion: DRT is inversely associated with UFR in CHD patients. Whether a high UFR should be recommended to reduce the DRT needs to be elucidated through an adequate prospective randomized study.

ContextFatigue is one of the most prevalent symptoms among hemodialysis (HD) patients. To design effective treatments, it is crucial to understand the diurnal pattern of fatigue in this population.ObjectivesThe objectives of this study were to assess diurnal changes in fatigue in patients undergoing hemodialysis and their relation with depressive symptoms and to explore whether fatigue may become a classically conditioned response to the hospital environment.MethodsA prospective, observational study was conducted in 51 HD patients. Subjects repeatedly rated their current fatigue on three different days during one week of hemodialysis treatment to capture changes in momentary fatigue. First, on an HD treatment day, fatigue was measured one hour before and immediately before dialysis, as well as immediately after dialysis and again at 22:00 pm Second, on the postdialysis day and on the seventh weekday (when patients had not received treatment on the previous day), fatigue was measured at the same moments in time as the two measurements before dialysis on the treatment day. Beck Depression Inventory-II and Fatigue Severity Scale were administered to evaluate depressive mood and fatigue severity in daily life.ResultsFatigue increased as a result of hemodialysis treatment over the entire sample. However, diurnal fatigue patterns differed significantly between individuals high and low in depressive symptoms, with the former being fatigued more constantly throughout the day, and the latter experiencing increases in fatigue due to treatment. Pretreatment fatigue experienced in the hospital environment followed a pattern consistent with the development of a classically conditioned response.ConclusionDiurnal fatigue patterns during hemodialysis treatment are associated with depressive symptoms, and classical conditioning may play a role in the experience of pretreatment fatigue.

Xerostomia, or dryness of oral cavity, is relatively common in patients on chronic hemodialysis and significantly impairs their quality of life. Xerostomia is often the consequence of reduced salivary flow resulting from atrophy and fibrosis of the salivary glands, an event that is of uncertain origin. Many medications commonly used in dialysis patients may also cause or exacerbate xerostomia. Its consequences may be serious and disturbing and include difficulties in chewing, swallowing, tasting, and speaking; increased risk of oral disease, including lesions of the mucosa, gingiva and tongue; bacterial and fungal infections, such as candidiasis, dental caries, and periodontal disease; interdialytic weight gain resulting from increased fluid intake; and a reduction in the quality of life. Therapeutically, stimulation of the salivary glands to increase the production of saliva mechanically by chewing-gum, mouthwash, acupressure, or transcutaneous electrical stimulation has had modest success. However, the long-term effectiveness of such treatments still needs to be investigated and defined. Xerostomia remains a frustrating and disturbing symptom for patients on hemodialysis. Further efforts should be made to find the causes and the mechanisms of the reduced salivary flow observed in patients on chronic hemodialysis.

Postdialysis fatigue (PDF) is a frequent and debilitating symptom of patients on chronic hemodialysis that affects their daily living and quality of life. Little is known about the mechanisms underlying this symptom and its severity. Only a few studies have investigated therapeutic interventions and with conflicting results. Given the major impact of PDF on the quality of life of hemodialysis patients, a larger effort is warranted to better understand, prevent, and treat PDF.

Aim Data on the outcome of chronic kidney disease (CKD) patients who are hospitalized and start unplanned urgent haemodialysis (HD) are lacking. This prospective, longitudinal, observational study aimed to define the hospital mortality rate and associated factors in CKD patients who start unplanned urgent HD. Methods Between January 2003 and December 2009, all patients with CKD who were hospitalized, diagnosed with ESRD and started unplanned urgent haemodialysis at Haemodialysis Service of the Catholic University of Rome, Italy were recruited. Exclusion criteria were: acute renal failure, prior history of dialysis, multiple organ failure, coma, and dementia. Hospital mortality rate was the primary outcome. Results Three and hundred sixteen patients were studied: 99 died after 19.5 ± 27.3 days and 217 survived until discharge. Of these, 154 were prescribed chronic HD and 63 restored renal function. Patients who died were significantly older and had a higher Charlson Comorbidity Index score. The mortality rates were 51.1% in patients with 81–90 years, 37.8% with 71–80 years, 34.1% with 61–70 years and 13.9% with age ≤60 years. Logistic regression analysis showed that age only was an independent risk factor for all-cause mortality. Conclusions In CKD patients who need hospitalization and start unplanned urgent haemodialysis the mortality is very high and significantly related to age.

Background: To measure daily sodium intake in patients on chronic hemodialysis and to compare the intake of nutrients, minerals, trace elements, and vitamins in patients who had a daily sodium intake below or above the value of 1500 mg recommended by the American Heart Association. Methods: Dietary intake was recorded for 3 days by means of 3-day diet diaries in prevalent patients on chronic hemodialysis. Each patient was instructed by a dietitian on how to fill the diary, which was subsequently signed by a next of kin. Results: We studied 127 patients. Mean sodium intake (mg) was 1295.9 &plusmn, 812.3. Eighty-seven (68.5%) patients had a daily sodium intake &lt, 1500 mg (group 1) and 40 (31.5%) &ge, 1500 mg (group 2). Correlation between daily sodium intake and daily calorie intake was significant (r = 0.474 [0.327 to 0.599], p &lt, 0.0001). Daily calorie intake (kcal/kg/day) was lower in group 1 (21.1 &plusmn, 6.6, p = 0.0001) than in group 2 (27.1 &plusmn, 10.4). Correlation between daily sodium intake and daily protein intake was significant (r = 0.530[0.392 to 0.644], 0.0001). The daily protein intake (grams/kg/day) was lower in group 1 (0.823 &plusmn, 0.275, p = 0.0003) than in group 2 (1.061 &plusmn, 0.419). Daily intake of magnesium, copper, iron, zinc, and selenium was significantly lower in group 1 than in group 2. Daily intake of vitamin A, B2, B3, and C did not differ significantly between group 1 and group 2. Daily intake of vitamin B1 was significantly lower in group 1 than in group 2. Significantly lower was, in group 1 than in group 2, the percentage of patients within the target value with regard to intake of calories (11.5% vs. 37.5%, p = 0.001) and proteins (9.2% vs. 27.5%, p = 0.015) as well as of iron (23% vs. 45%, p = 0.020), zinc (13.8% vs. 53.8%, p = 0.008) and vitamin B1 (8.1% vs. 50%, 0.001). Conclusion: A low daily intake of sodium is associated with an inadequately low intake of calorie, proteins, minerals, trace elements, and vitamin B1. Nutritional counselling aimed to reduce the intake of sodium in patients on chronic hemodialysis should not disregard an adequate intake of macro- and micronutrients, otherwise the risk of malnutrition is high.

Physical frailty and sarcopenia (PF&amp, S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&amp, S. In this initial report, 68 community-dwellers aged 70 years and older, 38 with PF&amp, S and 30 non-sarcopenic, non-frail controls (nonPF&amp, S), were enrolled as part as the &ldquo, BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons&rdquo, (BIOSPHERE) study. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares&ndash, Discriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&amp, S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 &plusmn, 3.9% (75.1 &plusmn, 4.6% for enrollees with PF&amp, S, 78.5 &plusmn, 6.0% for nonPF&amp, S). Older adults with PF&amp, S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&amp, S participants was defined by higher concentrations of &alpha, aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older people with PF&amp, S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions.

Mitochondrial dysfunction is a relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at a non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the hearts of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n = 8) or placebo (n = 8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and the abundance of mtDNA4834 deletion), and the mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. The binding of mitochondrial transcription factor A to mtDNA regions involved in replication and deletion generation was enhanced following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling were found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.

Background and aim Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in old age. Neurotoxicity of dopaminergic neurons triggered by aggregation of misfolded α-synuclein is a major pathogenic trait of PD. However, growing evidence indicates that peripheral processes, including metabolic changes, may precede and contribute to neurodegeneration. The present study was undertaken to identify a metabolic signature of PD through the quantification of serum amino acids and derivatives. Participants and methods Twenty older adults with PD (11 men and 9 women; mean age 73.1 ± 10.2 years) and 30 age-matched controls (14 men and 16 women; mean age 74.6 ± 4.3 years) were enrolled. A panel of 37 serum amino acids and derivatives was assessed by ultra-performance liquid chromatography/mass spectrometry. Partial least squares − discriminant analysis (PLS-DA) followed by double cross-validation was used to characterize the relationship between amino acid profiles and PD. Results The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classifications was 99.3 ± 2.5% for participants with PD and 94.7 ± 3.0% for non-PD controls. Higher levels of β-amino butyric acid, cystine, ornithine, phosphoethanolamine, and proline defined the circulating amino acid profile of older people with PD. Controls were characterized by higher concentrations of 3-methyl-histidine, citrulline, and serine. Conclusion Our findings indicate the existence of a distinct metabotype in older persons with PD. Future studies will have to establish whether changes in amino acid metabolism are involved in the pathogenesis of PD. This knowledge may be harnessed to identify novel disease biomarkers as well as new targets for interventions.

The symptom burden of fatigued hemodialysis patients is poorly known. We aimed to investigate possible differences in the prevalence and severity of symptoms between fatigued and not fatigued patients on chronic hemodialysis. All prevalent patients on chronic hemodialysis referring to the Hemodialysis Service between January 2016 and June 2017 were considered eligible. The Dialysis Symptom Index (DSI) questionnaire was performed during the dialysis treatment. Patients underwent assessment of fatigue using the Italian version of the vitality scale of the SF-36 (SF-36VS). We studied 137 patients: 107 (78.1%) were fatigued and 30 (31.9%) were non-fatigued. The median [95% CI] number of symptoms was 15 [14–16] for patients who reported fatigue and 9 [8–19] for the non-fatigued (P

International audience; Fatigue is one of the most highly prioritized outcomes for patients and clinicians, but remains infrequently and inconsistently reported across trials in hemodialysis. We convened an international Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) consensus workshop with stakeholders to discuss the development and implementation of a core outcome measure for fatigue. 15 patients/caregivers and 42 health professionals (clinicians, researchers, policy makers, and industry representatives) from 9 countries participated in breakout discussions. Transcripts were analyzed thematically. 4 themes for a core outcome measure emerged. Drawing attention to a distinct and all-encompassing symptom was explicitly recognizing fatigue as a multifaceted symptom unique to hemodialysis. Emphasizing the pervasive impact of fatigue on life participation justified the focus on how fatigue severely impaired the patient's ability to do usual activities. Ensuring relevance and accuracy in measuring fatigue would facilitate shared decision making about treatment. Minimizing burden of administration meant avoiding the cognitive burden, additional time, and resources required to use the measure. A core outcome measure that is simple, is short, and includes a focus on the severity of the impact of fatigue on life participation may facilitate consistent and meaningful measurement of fatigue in all trials to inform decision making and care of patients receiving hemodialysis.

Mitochondrial structural and functional integrity is maintained through the coordination of several processes (e.g., biogenesis, dynamics, mitophagy), collectively referred to as mitochondrial quality control (MQC). Dysfunctional MQC and inflammation are hallmarks of aging and are involved in the pathogenesis of muscle wasting disorders, including sarcopenia and cachexia. One of the consequences of failing MQC is the release of mitochondria-derived damage-associated molecular patterns (DAMPs). By virtue of their bacterial ancestry, these molecules can trigger an inflammatory response by interacting with receptors similar to those involved in pathogen-associated responses. Mitochondria-derived DAMPs, especially cell-free mitochondrial DNA, have recently been associated with conditions characterized by chronic inflammation, such as aging and degenerative diseases. Yet, their actual implication in the aging process and muscle wasting disorders is at an early stage of investigation. Here, we review the contribution of mitochondria-derived DAMPs to age-related systemic inflammation. We also provide arguments in support of the exploitation of such signaling pathways for the management of muscle wasting conditions.

Sarcopenia is a well-known geriatric syndrome that has been endorsed over the years as a biomarker allowing for the discrimination, at a clinical level, of biological from chronological age. Multiple candidate mechanisms have been linked to muscle degeneration during sarcopenia. Among them, there is wide consensus on the central role played by the loss of mitochondrial integrity in myocytes, secondary to dysfunctional quality control mechanisms. Indeed, mitochondria establish direct or indirect contacts with other cellular components (e.g. endoplasmic reticulum, peroxisomes, lysosomes/vacuoles) as well as the extracellular environment through the release of several biomolecules. The functional implications of these interactions in the context of muscle physiology and sarcopenia are not yet fully appreciated and represent a promising area of investigation. Here, we present an overview of recent findings concerning the interrelation between mitochondrial quality control processes, inflammation and the metabolic regulation of muscle mass in the pathogenesis of sarcopenia highlighting those pathways that may be exploited for developing preventive and therapeutic interventions against muscle aging.

Functional impairment is associated with adverse outcomes in older people, as well as in patients on chronic hemodialysis. The aim of this study was to evaluate if functional impairment represents a risk factor for reduced survival in patients on chronic hemodialysis. All incident chronic hemodialysis patients of Lazio, a large region of central Italy, registered in the Dialysis and Transplant Lazio Region Registry (DTLRR) in the period 2008–2013 were considered eligible. Inclusion criteria were: age > 18 years, resident in Lazio, still doing dialysis after 90 days from incidence date, doing hemodialysis or hemodiafiltration treatment for > 9 h/week. Patients were stratified into three classes of functional activity: total autonomy, autonomy in some activities, and not self-sufficient. Functional activity was assessed for each patient by the referring physician for the DTLRR from the ~ 90 hemodialysis units of the Lazio region. Each patient was followed from date of first dialysis treatment to the end of the study (31/12/2015) or death or renal transplant, whichever occurred first. Cox proportional hazard models were performed to obtain mortality hazard ratios (HR), 95% confidence intervals (CI), for each class of functional activity adjusting for sex, age, country of birth, city of residence, body mass index (BMI), type of nephropathy, vascular access, previous nephrology counselling, weekly hours of hemodialysis, serum albumin, hemoglobin, and presence of comorbidities (e.g. vascular diseases, coronary disease, and diabetes). A total of 3356 patients were studied. In the whole follow-up period, 1622 deaths occurred (48%). Functional impairment was associated with the risk of mortality: compared to ‘total autonomy’, the HR for ‘autonomy in some activities’ was 1.30 [95% CI: 1.14–1.49] and for ‘not self-sufficient’ 1.71 [1.47–1.99] (p for trend

In secondary hyperparathyroidism (SHPT), ultrasonography (US) can accurately define the size and structure of parathyroid glands as well as differentiate diffuse and nodular hyperplasia. US may be also useful to predict the response of SHPT to vitamin D analogs and cinacalcet and to assess for regression of parathyroid glands hyperplasia by measurement of parathyroid gland volume. There is increasing evidence that US can potentially identify patients who will benefit from prompt surgical intervention. Therefore, US should be part of the diagnostic armamentarium in the treatment of SHPT in the daily clinical practice.

A significant percentage of patients on chronic hemodialysis have an interdialytic weight gain (IDWG) above the recommended values. High IDWG has detrimental effects on survival, cardiovascular outcomes, and quality of life. High IDWG is secondary to poor adherence to fluid restriction and to excessive intake of fluids, due to thirst and xerostomia. Various strategies have been proposed to limit IDWG such as the reduction of dietary salt intake, behavioral interventions aimed at improving the adherence to fluid restriction, the improvement of xerostomia, and the use of lower dialysate sodium concentration. The present narrative review aims to evaluate the efficacy of each of such strategies.

Background Exposure to heavy metals has been associated with kidney disease. We investigated the spatial distribution of kidney disease in the industrially contaminated site of Taranto. Methods Cases were subjects with a first hospital discharge diagnosis of kidney disease. Cases affected by specific comorbidities were excluded. Standardized Hospitalization Ratios (SHRs) were computed for low/high exposure area and for modeled spatial distribution of cadmium and fine particulate matter. Result Using the high/low exposure approach, in subjects aged 20-59 years residing in the high exposure area a significant excess of hospitalization was observed in males and a non-significant excess in females. No excesses were observed in subjects aged 60 years and over. The analysis by the modeling approach did not show a significant association with the greatest pollution impact area. Conclusion Due to the excesses of hospitalization observed in the high/low exposure approach, a continuing epidemiological surveillance of residents and occupational groups is warranted.

Health-related quality of life (HRQOL) in patients on chronic hemodialysis has not improved significantly in the last 20 years. This is largely due to their substantial symptom burden which is rarely assessed and treated in routine clinical practice. It also is a consequence of the lack of an appropriate armamentarium for the treatments of such symptoms. Adequate studies on the causes and pathogenesis of the symptoms of hemodialysis patients are needed followed by high quality studies on possible therapeutic pharmacological and nonpharmacological interventions.

Objectives The clinical practice guidelines published by the Renal Physicians Association (USA) recommend instituting advance care planning (ACP) for patients with end-stage renal disease. Studies on this issue are lacking in Italy. Our aim was to determine the attitudes of patients on ACP in our dialysis centre. Methods We performed a cross-sectional survey. We recruited patients on maintenance haemodialysis (HD) at Hemodialysis Center of Universita Cattolica del Sacro Cuore, from 1 March 2014 to 31 March 2015. The only exclusion criterion was inability to give an informed consent. Patients completed a questionnaire concerning their treatment preferences in three hypothetical disease scenarios: persistent vegetative state, advanced dementia, severe terminal illness; for each patients, we also collected clinical, functional and socioeconomic data. Results Thirty-four HD outpatients completed the study questionnaire. The majority of respondents (85%) considered information about prognosis, health conditions and treatment options, including withdrawing dialysis, as very important and 94% of respondents considered treatment of uraemic/dialytic symptoms the most important issue. In the health scenarios provided, dialysis was the treatment least withheld. Dependence on instrumental activities of daily living (0.048) and higher Charlson Comorbidity Index scores (p = 0.035) were associated with continuing dialysis in at least one scenario. Conclusions ACP should be tailored to patients’ value, culture and preferences. A significant proportion of patients, however, do not want to be involved in end of life decisions. Frail elderly patients, in particular, are not inclined to interrupt dialysis, despite poor quality of life or a poor prognosis.

Introduction and Aims: Serum p-cresyl sulfate associates with cardiovascular disease in patients at different stages of chronic kidney disease. p-Cresyl sulfate concentrations are determined by intestinal uptake of p-cresol, human metabolism to p-cresyl sulfate and renal clearance. Whether intestinal uptake of p-cresol itself is associated with cardiovascular disease in patients with renal disease has not been studied to date. Methods: We performed a prospective study in patients with chronic kidney disease stage 1-5 (clinicaltrials.gov NCT00441623). Intestinal uptake of p-cresol, under steady state conditions, was estimated from 24h urinary excretion of p-cresyl sulfate. Primary endpoint was time to first cardiovascular event, i.e. cardiac death, myocardial infarction/ischemia, ventricular arythmia, cardiovascular surgery, cerebrovascular accident or symptomatic peripheral arterial disease. Statistical analysis was done using Kaplan Meier estimates and Cox proportional hazard analyses. Results: In a cohort of 200 patients, median 24h urinary excretion of p-cresyl sulfate was 457.47 µmol (IQR 252.68-697.17). After a median follow-up of 52 months, 25 patients reached the primary endpoint (tertile 1/2/3: 5/6/14 events, log rank P 0.0368, see figure). Higher urinary excretion of p-cresyl sulfate was related with cardiovascular events (univariate hazard ratio per 100 µmol increase: 1.112, P 0.0015). In multivariate analysis, urinary excretion of p-cresyl sulfate remained a predictor of cardiovascular events, independent of markers of renal function (Hazard ratio 1.120, P 0.0022) and in different models with other cardiovascular risk factors (Framingham risk factors, cardiovascular history, diabetes mellitus and biochemical parameters). The independent association between urinary excretion of p-cresyl sulfate and outcome persisted after correction for serum p-cresyl sulfate. Conclusions: Intestinal uptake of p-cresol associates with cardiovascular disease independent of renal function. Insights into mechanisms governing intestinal generation and absorption of p-cresol may lead to identification of novel therapeutic targets to reduce cardiovascular disease risk in patients with chronic kidney disease.