Search Results (24)

Sarcopenia, defined as the progressive loss of skeletal muscle mass and strength, is increasingly recognized as a significant concern in patients with chronic kidney disease (CKD) and particularly in kidney transplant recipients (KTx-ps). This review explores the complex interplay of pathophysiological mechanisms, prevalence, and management strategies of sarcopenia in the context of kidney transplantation. CKD contributes to sarcopenia through systemic inflammation, malnutrition, uremic toxin accumulation, and metabolic imbalances, all of which persist or are exacerbated after transplantation due to immunosuppressive therapies especially corticosteroids. Notably, the post-transplant period may introduce additional risks, such as altered body composition and reduced physical activity, further aggravating muscle wasting. Sarcopenia affects approximately 26% of KTx-ps, leading to adverse outcomes including decreased quality of life, increased risk of infection, frailty, delayed recovery, and graft loss. The diagnosis remains challenging due to variability in assessment tools and a lack of standardized criteria. Management strategies must be multifactorial, including personalized nutritional support, targeted physical activity, and, where appropriate, pharmacological interventions. Early identification through imaging and functional testing is critical, especially in older patients and those with prolonged dialysis vintage. Emerging therapies, such as myostatin inhibitors, offer promise but require further validation. Additionally, early steroid withdrawal may mitigate muscle loss without compromising graft survival in selected patients. This review underscores the need for heightened awareness and standardized protocols to identify and manage sarcopenia in kidney transplantation, ultimately improving long-term outcomes and patient-centered care. Full article

Chronic kidney disease (CKD) is on the rise, with sarcopenia accompanying CKD in an estimated 25% of patients, featuring as a potentially debilitating issue that should not be overlooked. Sarcopenia, characterized by a loss of skeletal muscle mass and strength, is multifactorial. The aging process, uremic toxins, systemic inflammation, oxidative stress, gut dysbiosis, hormonal dysregulation, dietary deficits, and even air pollution are among the major parameters being implicated in sarcopenia among patients with CKD. Additionally, the existence of various comorbidities, such as type 2 diabetes mellitus (T2DM), depression, and cardiovascular diseases (CVD), also contribute to the chronic low-grade inflammation associated with skeletal muscle inflammation and atrophy. The purpose of this review is to delve into the complex interplay of multiple factors being involved in the pathogenesis of sarcopenia in patients with CKD. Moreover, we aim to shed light upon nutritional aspects that could delay the development and progression of sarcopenia among patients with CKD. To address vitamin D deficiency, micronutrients and macronutrients together with physical activity remain the cornerstone of delaying the progression of sarcopenia in this sub-population. Additionally, experimental drugs exhibiting therapeutic potential are also being discussed. As sarcopenia and quality of life are interconnected, the timely recognition of sarcopenia, together with nutritional and therapeutic interventions, is of the utmost importance in our crusade for a better quality of life (QoL) in patients with CKD. Full article

Background: Hemodialysis (HD) patients frequently develop muscle wasting and chronic inflammation, conditions associated with functional decline and reduced quality of life (QoL). Nutritional strategies that provide targeted anabolic support without increasing nitrogen load may offer clinical benefits. The aim of this study was to evaluate the possible impact of a food for special medical purposes (FFSMP), composed of free-form branched-chain amino acids, β-hydroxy-β-methylbutyrate, and zinc, on muscle mass and strength, laboratory parameters, physical performance (PP), and QoL in HD patients. Methods: in this randomized double-blind crossover study, 24 adult HD patients received the FFSMP (10 g/day; two sachets) supplementation or placebo for 12 weeks, separated by an 8-week wash-out (protocol code RS 29.23). Measured outcomes included quadriceps rectus femoris thickness (QRFT) muscle, body composition analysis, inflammatory markers, oxidative stress indices, other routine biochemical parameters, PP, and QoL (SF-36 questionnaire). Results: FFSMP supplementation resulted in significant increases in QRFT and in fat-free mass percentage. Reductions in oxidative stress and inflammatory biomarkers were observed. Routine biochemical parameters remained stable, with the exception of a decrease in pre-dialysis urea. Functional performance measures did not differ between treatment periods. Improvements were noted in selected SF-36 domains, specifically energy/fatigue and general health. No major adverse events occurred during the study. Conclusions: In HD patients, this FFSMP produced favorable changes in markers of muscle mass and systemic inflammation without affecting short-term physical performance. These findings support the potential clinical utility of targeted amino acid supplementation in this patient population, highlighting the need for larger, longer-term trials. Full article

Chronic kidney disease (CKD), which affects over 850 million individuals globally, is increasingly regarded as a systemic condition in which the gut microbiota represents a key pathogenic node. This review provides an integrated overview of mechanistic, translational and clinical data implicating the gut–kidney axis in CKD. The CKD-associated microbiota displays a characteristic dysbiosis, marked by depletion of short-chain fatty acid–producing commensals, overgrowth of proteolytic and urease-expressing taxa and disruption of epithelial barrier integrity. These disturbances favor the generation and systemic accumulation of gut-derived uremic toxins, most notably indoxyl sulfate, p-cresyl sulfate, indole-3-acetic acid and trimethylamine-N-oxide, which promote endothelial dysfunction, vascular calcification, fibrosis and chronic inflammation, thereby hastening renal function loss and heightening cardiovascular risk. Microbiome-directed interventions, including dietary modification, prebiotics, probiotics, synbiotics, intestinal dialysis, fecal microbiota transplantation, gut-acting sorbents and nephroprotective phytochemicals, are summarized with emphasis on their effects on uremic toxin burden and clinical surrogates. System-level implications of the gut–kidney axis for cardiovascular disease, immunosenescence and sarcopenia are discussed, together with future priorities for integrating multi-omics profiling and precision microbiome-based strategies into nephrology practice. Full article

Chronic kidney disease (CKD) is a leading condition in terms of prevalence and overall health impact. With the increased life expectancy of the CKD population and the improvement in medical care, controlling musculoskeletal complications remains a tough challenge. Patients with CKD are prone to falls, fractures and sarcopenia, enhancing the risk of death. A multitude of mechanisms contribute to fractures, and treatment is suboptimal; therefore, prevention must stand out as a key step. This review aims to provide an overview of the most relevant data regarding the impact of nutrition on bone disorders and sarcopenia in CKD. The newest relevant studies emphasize that plant protein intake is associated with a lower production of uremic toxins, lower serum phosphorus levels, and stronger bones. We conclude that patients with CKD should adopt specific diets tailored to the presence of osteoporosis, renal osteodystrophy, and muscle wasting. Low-protein diets or plant-dominant diets containing an adequate amount of protein could be better choices for predialysis patients with CKD in order to protect their bones and muscles, whereas in the dialysis population, a higher protein intake could be essential to prevent osteoporosis and sarcopenia. In all patients with CKD, focusing on antioxidant food intake could provide a strong antiaging benefit through ensuring good musculoskeletal health. Full article

Background: Chronic kidney disease (CKD) will become the fifth leading cause of death in the world by 2040. It is fundamental to prevent and treat this pathology to reduce its impact on national health costs. This trial’s aim is to evaluate the effects induced by a combination of consumed functional foods (FFs) with adapted physical activity (APA) on the progression of CKD-related comorbidities. Methods: The study lasted 12 weeks. We divided 40 CKD patients into four groups: mixed (FF + APA), APA, FF and control group (usual care). The FFs were characterized by their total antioxidant capacity and antiradical activity. The APA was performed though an online training protocol, three times per week, 1 h each session. Results: At the end of the study, we observed, in the mixed group, a decrease in azotemia (p = 0.0272), diastolic blood pressure (p = 0.0169), and C-reactive protein (p = 0.0313), with increases in the FORD test (p = 0.0203) and fat free mass (p = 0.0258). The APA group showed a reduction in total cholesterol (p = 0.0039). Conclusions: The combination of FFs and APA can help counteract several CKD-related comorbidities, such as arterial hypertension, dyslipidemia and uremic sarcopenia, and improve the CKD patients’ quality of life. Full article

Chronic kidney disease (CKD) is associated with significant reductions in lean body mass and in the mass of various tissues, including skeletal muscle, which causes fatigue and contributes to high mortality rates. In CKD, the cellular protein turnover is imbalanced, with protein degradation outweighing protein synthesis, leading to a loss of protein and cell mass, which impairs tissue function. As CKD itself, skeletal muscle wasting, or sarcopenia, can have various origins and causes, and both CKD and sarcopenia share common risk factors, such as diabetes, obesity, and age. While these pathologies together with reduced physical performance and malnutrition contribute to muscle loss, they cannot explain all features of CKD-associated sarcopenia. Metabolic acidosis, systemic inflammation, insulin resistance and the accumulation of uremic toxins have been identified as additional factors that occur in CKD and that can contribute to sarcopenia. Here, we discuss the elevation of systemic phosphate levels, also called hyperphosphatemia, and the imbalance in the endocrine regulators of phosphate metabolism as another CKD-associated pathology that can directly and indirectly harm skeletal muscle tissue. To identify causes, affected cell types, and the mechanisms of sarcopenia and thereby novel targets for therapeutic interventions, it is important to first characterize the precise pathologic changes on molecular, cellular, and histologic levels, and to do so in CKD patients as well as in animal models of CKD, which we describe here in detail. We also discuss the currently known pathomechanisms and therapeutic approaches of CKD-associated sarcopenia, as well as the effects of hyperphosphatemia and the novel drug targets it could provide to protect skeletal muscle in CKD. Full article

Chronic kidney disease (CKD) is a global health problem. In patients with CKD, exercise endurance is decreased, especially as renal dysfunction advances. This is due to the combined effects of protein-energy wasting, uremic acidosis, and inflammatory cachexia, which lead to sarcopenia and are aggravated by a sedentary lifestyle, resulting in a progressive downward spiral of deconditioning. Renal rehabilitation (RR) is a coordinated, multifaceted intervention designed to optimize a patient’s physical, psychological, and social functioning, as well as to stabilize, slow, or even reverse the progression of renal deterioration, improving exercise tolerance and preventing the onset and worsening of heart failure, thereby reducing morbidity and mortality. This review focused on the history and benefits of RR in patients with CKD. Based on current evidence, RR is an effective, feasible, and safe secondary prevention strategy in CKD. RR is a promising model for a new field of rehabilitation. Therefore, efforts to increase RR implementation rates are urgently needed. Full article

Patients with chronic kidney disease (CKD) often experience a high accumulation of protein-bound uremic toxins (PBUTs), specifically indoxyl sulfate (IS) and p-cresyl sulfate (pCS). In the early stages of CKD, the buildup of PBUTs inhibits bone and muscle function. As CKD progresses, elevated PBUT levels further hinder bone turnover and exacerbate muscle wasting. In the late stage of CKD, hyperparathyroidism worsens PBUT-induced muscle damage but can improve low bone turnover. PBUTs play a significant role in reducing both the quantity and quality of bone by affecting osteoblast and osteoclast lineage. IS, in particular, interferes with osteoblastogenesis by activating aryl hydrocarbon receptor (AhR) signaling, which reduces the expression of Runx2 and impedes osteoblast differentiation. High PBUT levels can also reduce calcitriol production, increase the expression of Wnt antagonists (SOST, DKK1), and decrease klotho expression, all of which contribute to low bone turnover disorders. Furthermore, PBUT accumulation leads to continuous muscle protein breakdown through the excessive production of reactive oxygen species (ROS) and inflammatory cytokines. Interactions between muscles and bones, mediated by various factors released from individual tissues, play a crucial role in the mutual modulation of bone and muscle in CKD. Exercise and nutritional therapy have the potential to yield favorable outcomes. Understanding the underlying mechanisms of bone and muscle loss in CKD can aid in developing new therapies for musculoskeletal diseases, particularly those related to bone loss and muscle wasting. Full article

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

Alterations in muscle structure and function in chronic kidney disease (CKD) patients are associated with poor outcomes. As key organelles in muscle cell homeostasis, mitochondrial metabolism has been studied in the context of muscle dysfunction in CKD. We conducted a study to determine the contribution of oxidative metabolism, glycolysis and fatty acid oxidation to the muscle metabolism in CKD. Mice developed CKD by exposure to adenine in the diet. Muscle of CKD mice showed significant weight loss compared to non-CKD mice, but only extensor digitorum longus (EDL) muscle showed a decreased number of fibers. There was no difference in the proportion of the various muscle fibers in CKD and non-CKD mice. Muscle of CKD mice had decreased expression of proteins associated with oxidative phosphorylation but increased expression of enzymes and transporters associated with glycolysis. In cell culture, myotubes exposed to uremic serum demonstrated decreased oxygen consumption rates (OCR) when glucose was used as substrate, conserved OCR when fatty acids were used and increased lactate production. In conclusion, mice with adenine-induced CKD developed sarcopenia and with increased glycolytic metabolism but without gross changes in fiber structure. In vitro models of uremic myopathy suggest fatty acid utilization is preserved compared to decreased glucose utilization. Full article

Serum myostatin and indoxyl sulfate (IS) levels increase with kidney function decline and may function as uremic toxins in chronic kidney disease (CKD)-related sarcopenia. Herein, we analyzed the association between serum myostatin and IS levels and sarcopenia in patients with CKD, by performing a post hoc analysis of baseline data extracted from the RECOVERY study (clinicaltrials.gov: NCT03788252) of 150 patients with CKD. We stratified patients into two groups according to the median value of myostatin (cutoff 4.5 ng/mL) and IS levels (cutoff 0.365 mg/dL). The proportion of patients with sarcopenia was higher in those with high IS levels but lower in those with high myostatin levels. The skeletal muscle mass index (SMI) and handgrip strength (HGS) were significantly lower in patients with high IS levels but significantly higher in patients with high myostatin levels. IS levels showed a negative correlation with glomerular filtration rate (GFR), SMI, and HGS. However, myostatin levels were positively correlated with SMI and HGS, but not with GFR. Sarcopenia was independently associated with age and IS level after adjustment. Increased levels of serum total IS might play a role in sarcopenia, while increased levels of serum myostatin are associated with muscle mass in patients with CKD. Full article

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

Chronic kidney disease (CKD) represents a public health problem because it is characterized by several comorbidities, including uremic sarcopenia (US), and a poor quality of life. Currently, there are no standardized treatments available to counteract the onset of US but only some possible therapeutic approaches to slow its progression. The aim of this pilot study is to collect descriptive data in order to design a clinical trial based on the power analysis and simple size. The purpose of this pilot study was to evaluate the possible beneficial action induced by the functional anti-inflammatory and antioxidant bars in combination with the adapted physical activity (APA), on the onset and progression of US and other related-CKD comorbidities. We enrolled 21 CKD patients under conservative therapy, divided into four groups: (A) the physical exercise program (PEP), three times a week, in combination with the daily consumption of the two functional bars group; (B) the PEP group; (C) the daily consumption of the two functional bars group; (D) the control group. The duration of the study protocol was 12 weeks. We observed an improvement trend of body composition, blood pressure levels, lipid metabolism, and functional test in A and B groups. These preliminary data would seem to confirm the effectiveness of APA and to demonstrate the additive role of the natural bioactive compound’s assumption in countering US and other CKD comorbidities. Full article

Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia. Furthermore, we investigated whether in these patients, there was any association between gMB, uremic toxins, inflammation and oxidative stress. We analyzed gMB composition, uremic toxins (indoxyl sulphate and p-cresyl sulphate), inflammatory cytokines (interleukin 10, tumor necrosis factor α, interleukin 6, interleukin 17, interleukin 12 p70, monocyte chemoattractant protein-1 and fetuin-A) and oxidative stress (malondialdehyde) of 64 elderly CKD patients (10 < eGFR < 45 mL/min/1.73 m², not on dialysis) categorized as sarcopenic and not-sarcopenic. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 criteria. Sarcopenic patients had a greater abundance of the Micrococcaceae and Verrucomicrobiaceae families and of Megasphaera, Rothia, Veillonella, Akkermansia and Coprobacillus genera. They had a lower abundance of the Gemellaceae and Veillonellaceae families and of Acidaminococcus and Gemella genera. GMB was associated with uremic toxins, inflammatory cytokines and MDA. However, uremic toxins, inflammatory cytokines and MDA were not different in sarcopenic compared with not-sarcopenic individuals, except for interleukin 10, which was higher in not-sarcopenic patients. In older CKD patients, gMB was different in sarcopenic than in not-sarcopenic ones. Several bacterial families and genera were associated with uremic toxins and inflammatory cytokines, although none of these latter substantially different in sarcopenic versus not-sarcopenic patients. Full article