Association between the uremic toxins indoxyl-sulfate and p-cresyl-sulfate with sarcopenia and malnutrition in elderly patients with advanced chronic kidney disease

Caldiroli, Lara; Armelloni, Silvia; Eskander, Alessandra; Rizzo, Vittoria; Margiotta, Elisabetta; Cesari, Matteo; Vettoretti, Simone

doi:10.1016/j.exger.2021.111266

Cited by 20 publications

(15 citation statements)

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“…These results may at least partially depend on the correlations between poor nutritional status and sarcopenia in our patients. Indeed, in a previous study by our group conducted in older CKD patients, IS and pCS were oppositely associated with nutritional indices [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…Finally, IS induces atrophy of myotubes through the production of reactive oxygen species [ 12 ]. In patients with end stage renal disease in dialysis, there is a significant inverse association between plasma IS and skeletal muscle mass [ 11 ], but this association was not observed in older patients with advanced CKD not yet in dialysis [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…In addition to the role played by uremic toxins, it has recently been demonstrated that intestinal dysbiosis and gastrointestinal barrier disruption may significantly contribute to sustaining a low-grade systemic inflammation in CKD [ 11 , 12 ]. In CKD patients, gut dysbiosis is characterized by distinctive qualitative changes, such as increased the Enterobacteriaceae and reduced the Lactobacillaceae and Prevotellaceae families [ 13 , 14 , 15 ]. In our previous study, in which we compared CKD patients with healthy controls, we found that the former were characterized by increased abundance of the Citrobacter , Anaerotruncus , Coprobacillus genera and Ruminococcus torques species and reduced abundance of saccharolytic and butyrate-producing bacteria ( Prevotella , F. prausnitzii , Roseburia ) [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress

Margiotta

Caldiroli

Callegari

et al. 2021

Toxins

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Background: 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. Methods: 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. Results: 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. Conclusions: 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.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress

Margiotta

Caldiroli

Callegari

et al. 2021

Toxins

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“…Alterations in serum UT levels such as hippuric acid and oxoproline are also close proxies of physical inactivity in those of advanced age [58]. Despite the rare findings of a lack of associations between UTs and sarcopenia in small scale studies [59], overwhelming clinical reports derive consistent results that UT levels closely follow the severity of skeletal muscle loss, increasing the susceptibility to developing frailty, in CKD/ESRD patients [56][57][58].…”

Section: Other Utsmentioning

confidence: 99%

Uremic Toxins and Frailty in Patients with Chronic Kidney Disease: A Molecular Insight

Chao

Lin

2021

IJMS

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The accumulation of uremic toxins (UTs) is a prototypical manifestation of uremic milieu that follows renal function decline (chronic kidney disease, CKD). Frailty as a potential outcome-relevant indicator is also prevalent in CKD. The intertwined relationship between uremic toxins, including small/large solutes (phosphate, asymmetric dimethylarginine) and protein-bound ones like indoxyl sulfate (IS) and p-cresyl sulfate (pCS), and frailty pathogenesis has been documented recently. Uremic toxins were shown in vitro and in vivo to induce noxious effects on many organ systems and likely influenced frailty development through their effects on multiple preceding events and companions of frailty, such as sarcopenia/muscle wasting, cognitive impairment/cognitive frailty, osteoporosis/osteodystrophy, vascular calcification, and cardiopulmonary deconditioning. These organ-specific effects may be mediated through different molecular mechanisms or signal pathways such as peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), mitogen-activated protein kinase (MAPK) signaling, aryl hydrocarbon receptor (AhR)/nuclear factor-κB (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Runt-related transcription factor 2 (RUNX2), bone morphogenic protein 2 (BMP2), osterix, Notch signaling, autophagy effectors, microRNAs, and reactive oxygen species induction. Anecdotal clinical studies also suggest that frailty may further accelerate renal function decline, thereby augmenting the accumulation of UTs in affected individuals. Judging from these threads of evidence, management strategies aiming for uremic toxin reduction may be a promising approach for frailty amelioration in patients with CKD. Uremic toxin lowering strategies may bear the potential of improving patients’ outcomes and restoring their quality of life, through frailty attenuation. Pathogenic molecule-targeted therapeutics potentially disconnect the association between uremic toxins and frailty, additionally serving as an outcome-modifying approach in the future.

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“…PC is formed by gut bacterial fermentation of tyrosine and phenylalanine and has previously been described to promote the redistribution of total body fat and modify insulin resistance. A cross section study showed a positive association of PCs and protein-energy wasting with higher inflammatory markers of LogIL10 and logIL12p70 in sarcopenic patients with advanced CKD [ 31 ].…”

Section: Relationship Between Sarcopenic Obesity and Kidney Diseasementioning

confidence: 99%

The Role of Lifestyle Intervention, in Addition to Drugs, for Diabetic Kidney Disease with Sarcopenic Obesity

Chen

Liang

2022

Life

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Diabetic kidney disease is the leading cause of end-stage renal disease in developing and developed countries. The growing prevalence and clinical challenges of sarcopenic obesity have been associated with the frailty and disability of diabetic kidney disease. It has been reported that insulin resistance, chronic inflammation, enhanced oxidative stress and lipotoxicity contribute to the pathophysiology of muscle loss and visceral fat accumulation. Sarcopenic obesity, which is diagnosed with dual-energy X-ray absorptiometry, is associated with worse outcomes in kidney disease. Growing evidence indicates that adherence to healthy lifestyles, including low protein diet, proper carbohydrate control, vitamin D supplement, and regular physical training, has been shown to improve clinical prognosis. Based on the higher risk of sarcopenic-obesity-related renal function decline, it has led to the exploration and investigation of the pathophysiology, clinical aspects, and novel approach of these controversial issues in daily practice.

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Association between the uremic toxins indoxyl-sulfate and p-cresyl-sulfate with sarcopenia and malnutrition in elderly patients with advanced chronic kidney disease

Cited by 20 publications

References 42 publications

Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress

Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress

Uremic Toxins and Frailty in Patients with Chronic Kidney Disease: A Molecular Insight

The Role of Lifestyle Intervention, in Addition to Drugs, for Diabetic Kidney Disease with Sarcopenic Obesity

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