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"Uremia - therapy"
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Uremic Sarcopenia: Clinical Evidence and Basic Experimental Approach
2020
Sustained physical activity extends healthy life years while a lower activity due to sarcopenia can reduce them. Sarcopenia is defined as a decrease in skeletal muscle mass and strength due not only to aging, but also from a variety of debilitating chronic illnesses such as cancer and heart failure. Patients with chronic kidney disease (CKD), who tend to be cachexic and in frail health, may develop uremic sarcopenia or uremic myopathy due to an imbalance between muscle protein synthesis and catabolism. Here, we review clinical evidence indicating reduced physical activity as renal function deteriorates and explore evidence-supported therapeutic options focusing on nutrition and physical training. In addition, although sarcopenia is a clinical concept and difficult to recapitulate in basic research, several in vivo approaches have been attempted, such as rodent subtotal nephrectomy representing both renal dysfunction and muscle weakness. This review highlights molecular mechanisms and promising interventions for uremic sarcopenia that were revealed through basic research. Extensive study is still needed to cast light on the many aspects of locomotive organ impairments in CKD and explore the ways that diet and exercise therapies can improve both outcomes and quality of life at every level.
Journal Article
Inflammation and Premature Ageing in Chronic Kidney Disease
by
Ebert, Thomas
,
Pawelzik, Sven-Christian
,
Bäck, Magnus
in
ageing
,
Aging
,
Aging, Premature - metabolism
2020
Persistent low-grade inflammation and premature ageing are hallmarks of the uremic phenotype and contribute to impaired health status, reduced quality of life, and premature mortality in chronic kidney disease (CKD). Because there is a huge global burden of disease due to CKD, treatment strategies targeting inflammation and premature ageing in CKD are of particular interest. Several distinct features of the uremic phenotype may represent potential treatment options to attenuate the risk of progression and poor outcome in CKD. The nuclear factor erythroid 2-related factor 2 (NRF2)–kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1 (KEAP1) signaling pathway, the endocrine phosphate-fibroblast growth factor-23–klotho axis, increased cellular senescence, and impaired mitochondrial biogenesis are currently the most promising candidates, and different pharmaceutical compounds are already under evaluation. If studies in humans show beneficial effects, carefully phenotyped patients with CKD can benefit from them.
Journal Article
Once upon a time in dialysis: the last days of Kt/V?
by
Vanholder, Raymond
,
Eloot, Sunny
,
Glorieux, Griet
in
Biomarkers - blood
,
hemodialysis
,
Humans
2015
After its proposal as a marker of dialysis adequacy in the eighties of last century, Kt/Vurea helped to improve dialysis efficiency and to standardize the procedure. However, the concept was developed when dialysis was almost uniformly short and was applied thrice weekly with small pore cellulosic dialyzers. Since then dialysis evolved in the direction of many strategic alternatives, such as extended or daily dialysis, large pore high-flux dialysis, and convective strategies. Although still a useful baseline marker, Kt/Vurea no longer properly covers up for most of these modifications so that urea kinetics are hardly if at all representative for those of other solutes with a deleterious effect on morbidity and mortality of uremic patients. This is corroborated in several clinical studies showing a dissociation between removal of urea and that of other uremic toxins. In addition, randomized controlled trials showed no benefit of increasing Kt/Vurea. Finally, this parameter also hardly is evocative for metabolic or intestinal generation of toxins, for their removal by residual renal function and for the complex interaction of dialysis length with removal pattern and patient outcomes. We conclude that apart from being a baseline parameter of dialysis adequacy, Kt/Vurea insufficiently represents all novel strategic changes of modern dialysis. Kt/Vurea is too simple a concept for the complexities of uremia and of today’s dialysis.
Journal Article
Uremic toxins
by
Niwa, Toshimitsu
in
Kidney Failure, Chronic -- physiopathology
,
Kidney Failure, Chronic -- therapy
,
Mass Spectrometry
2012
Reviews all the latest basic and clinical research findings
With contributions from leading international experts in the field, this book is dedicated to all facets of uremic toxins research, including low molecular weight solutes, protein-bound solutes, and middle molecules. Moreover, it covers everything from basic mass spectrometry research to the latest clinical findings and practices.
Uremic Toxins is divided into three sections:
* Section One, Uremic Toxins, explores the definition, classification, listing, and mass spectrometric analysis of uremic toxins
* Section Two, Selected Uremic Toxins, describes key uremic toxins, explaining chemical structures, metabolism, analytical methods, plasma levels, toxicity, clinical implications, and removal methods. Among the uremic toxins covered are indoxyl sulfate, asymmetric dimethylarginine, PTH, ß2-microglobulin, and AGEs
* Section Three, Therapeutic Removal of Uremic Toxins, describes how uremic toxins can be removed by hemodialysis, peritoneal dialysis, and oral sorbent
All chapters are based on the authors' thorough review of the literature as well as their own personal laboratory and clinical experience. References at the end of each chapter provide a gateway to the literature in the field.
Reviewing all the latest basic and clinical research findings, Uremic Toxins will help bench scientists in nephrology advance their own investigations. It will also help clinicians take advantage of the latest tested and proven treatments for the management of chronic kidney disease.
Uremia
by
Meyer, Timothy W
,
Hostetter, Thomas H
in
Biological and medical sciences
,
Blood Urea Nitrogen
,
General aspects
2007
The meaning of uremia, which refers to the illness accompanying kidney failure that is unexplained by derangements in extracellular volume, inorganic ion concentrations, or lack of known renal synthetic products, has changed. We now assume that uremic illness is due largely to the accumulation of organic waste products, not all identified, that are normally cleared by the kidneys. This review considers the pathogenesis and course of uremia.
We now assume that uremic illness is due largely to the accumulation of organic waste products, not all identified, that are normally cleared by the kidneys. This review considers the pathogenesis and course of uremia.
Medical progress has altered the course and thus the definition of uremia, which once encompassed all the signs and symptoms of advanced kidney failure. Hypertension due to volume overload, hypocalcemic tetany, and anemia due to erythropoietin deficiency were once considered signs of uremia but were removed from this category as their causes were discovered. Today the term “uremia” is used loosely to describe the illness accompanying kidney failure that cannot be explained by derangements in extracellular volume, inorganic ion concentrations, or lack of known renal synthetic products. We now assume that uremic illness is due largely to the accumulation of . . .
Journal Article
Uremic toxins originating from colonic microbial metabolism
by
Meijers, Bjorn K.I.
,
Verbeke, Kristin
,
Bammens, Bert R.M.
in
bacterial protein metabolism
,
dietary modification
,
intestinal adsorbent therapy
2009
Numerous molecules, which are either excreted or metabolized by the kidney, accumulate in patients with chronic kidney disease (CKD). These uremic retention molecules (URMs), contributing to the syndrome of uremia, may be classified according to their site of origin, that is, endogenous metabolism, microbial metabolism, or exogenous intake. It is increasingly recognized that bacterial metabolites, such as phenols, indoles, and amines, may contribute to uremic toxicity. In vitro studies have implicated bacterial URMs in CKD progression, cardiovascular disease, and bone and mineral disorders. Furthermore, several observational studies have demonstrated a link between serum levels of bacterial URMs and clinical outcomes. Bacterial metabolism may therefore be an important therapeutic target in CKD. There is evidence that besides reduced renal clearance, increased colonic generation and absorption explain the high levels of bacterial URMs in CKD. Factors promoting URM generation and absorption include an increased ratio of dietary protein to carbohydrate due to insufficient intake of fiber and/or reduced intestinal protein assimilation, as well as prolonged colonic transit time. Two main strategies exist to reduce bacterial URM levels: interventions that modulate intestinal bacterial growth (e.g., probiotics, prebiotics, dietary modification) and adsorbent therapies that bind bacterial URMs in the intestines to reduce their absorption (e.g., AST-120, sevelamer). The efficacy and clinical benefit of these strategies are currently an active area of interest.
Journal Article
Uremic Toxins and Vascular Dysfunction
2020
Vascular dysfunction is an essential element found in many cardiovascular pathologies and in pathologies that have a cardiovascular impact such as chronic kidney disease (CKD). Alteration of vasomotricity is due to an imbalance between the production of relaxing and contracting factors. In addition to becoming a determining factor in pathophysiological alterations, vascular dysfunction constitutes the first step in the development of atherosclerosis plaques or vascular calcifications. In patients with CKD, alteration of vasomotricity tends to emerge as being a new, less conventional, risk factor. CKD is characterized by the accumulation of uremic toxins (UTs) such as phosphate, para-cresyl sulfate, indoxyl sulfate, and FGF23 and, consequently, the deleterious role of UTs on vascular dysfunction has been explored. This accumulation of UTs is associated with systemic alterations including inflammation, oxidative stress, and the decrease of nitric oxide production. The present review proposes to summarize our current knowledge of the mechanisms by which UTs induce vascular dysfunction.
Journal Article
Plasma beta-2 microglobulin is associated with cardiovascular disease in uremic patients
by
Vanholder, Raymond
,
Liabeuf, Sophie
,
Massy, Ziad A.
in
Aged
,
Aged, 80 and over
,
beta 2-Microglobulin - blood
2012
Since beta-2 microglobulin (B2M) is a surrogate marker for middle molecular weight uremic toxins and the major protein component in dialysis-related amyloidosis, it has been frequently studied in dialysis patients. It is not known, however, whether B2M has an impact in patients with chronic kidney disease (CKD) not yet on dialysis. Here we studied the relationship of plasma B2M levels to clinical and cardiovascular outcomes in 142 patients (mean age of 67 years) at different stages of CKD. B2M levels increased with CKD stage and thus were highest in hemodialysis patients. Baseline B2M levels were associated with vascular calcification but not with arterial stiffness or bone density. During a mean follow-up of 969 days, 44 patients died and 49 suffered a cardiovascular event. Higher B2M levels were independently associated with overall and cardiovascular mortality and cardiovascular events in the whole cohort and with cardiovascular events in the predialysis cohort. Moreover, B2M appeared to be a better predictor than well-established factors associated with outcomes in this population, such as estimated glomerular filtration rate ((eGFR), only for predialysis patients), inflammation biomarkers, and other factors included in a propensity score. Thus, we confirm the strong relationship between B2M levels and eGFR and confirm the power of B2M to predict overall and cardiovascular mortality and cardiovascular events in patients at different stages of CKD.
Journal Article
Acupuncture for uremic pruritus: A systematic review and meta-analysis protocol
by
Gao, Ning
,
Wang, Lei
,
Wang, Weiming
in
Acupressure
,
Acupuncture
,
Acupuncture Therapy - methods
2024
Uremic pruritus (UP) or chronic kidney disease-associated pruritus (CKD-aP) is one of the most intractable dermatologic symptom in patients with chronic kidney disease. Several randomized controlled trials (RCTs) have been conducted to investigate the antipruritic effects of acupuncture on UP/CKD-aP and suggested a significant therapeutic effect, while the evidence supporting the application of acupuncture is limited.
This study will assess the efficacy and safety of acupuncture for patients with UP/CKD-aP.
Data Sources: RCTs will be searched in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science, the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, Wanfang Database, VIP Database, the WHO International Clinical Trials Registry Platform portal and www.ClinicalTrials.gov from inception to 31st August 2024. Study eligibility criteria: RCTs in English and Chinese conducted on UP/CKD-aP patients will be included. Participants: Adult patients diagnosed with UP/CKD-aP will be included. Interventions: All acupuncture interventions in the management of UP/CKD-aP will be included, compared with no treatment, placebo or sham acupuncture, or other treatment agents. Outcome measures: The primary outcome will be the change in the severity of itching evaluated by validated scales. Study appraisal and svnthesis methods: If necessary, a meta-analysis will be performed for the pooled therapeutic effect by Review Manager 5.3, or a qualitative descriptive analysis will be presented. The data will be transformed into the risk ratio (RR) for binary data and the mean difference (MD) or standardized MD for continuous data for analysis.
This review will update evidence of RCTs evaluating acupuncture for UP/CKD-aP.
Anticipated challenges contain the methodological and clinical heterogeneity in terms of evaluation tools and acupuncture interventions within included studies.
It will benefit patients and impact health-care decision-making regarding the models of care that are feasible for patients.
PROSPERO CRD42021257001.
Journal Article
Prevalence of uremic neuropathy and the effect of dialysis in children with end-stage renal disease: A cohort study
2025
Children with chronic kidney disease (CKD) face increased morbidity, mortality, and reduced quality of life. Uremic neuropathy (UN) is a common neurological complication, but data on its relationship with dialysis in pediatric populations are limited. This prospective study aimed to assess the prevalence of UN in children with end-stage renal disease (ESRD) in a Tunisian population and explore the association between dialysis and UN. Conducted between July and September 2023 in the nephrology and neurophysiology units of a Tunisian hospital, the study included 31 children with CKD G5. Clinical data, biological analyses, and nerve conduction studies via electroneuromyography (EMG) were performed at baseline and six months later. Participants were divided into pre-dialysis and dialysis groups for comparison. The mean age was 11 ± 3.5 years, and the average age at CKD diagnosis was 7.5 ± 4.2 years. UN was diagnosed in 45% of participants using EMG, including 13% with silent neuropathy. Axonal neuropathy was predominant, with no cases of demyelinating neuropathy identified. Initial comparisons between dialysis and pre-dialysis groups showed no significant differences in UN characteristics. However, clinical neuropathy, weight-for-age, and glomerular nephritis were significantly associated with UN. Follow-up revealed a significant improvement in UN in the dialysis group. From this study, we conclude the importance of screening for UN in pediatric ESRD care and recommend routine EMG evaluations, even in asymptomatic patients, to ensure early diagnosis and management.
Journal Article