We searched PubMed, Embase, Web of Science, and the Cochrane Library for articles published in English up to Dec 1, 2015. Search terms related to the main topics of this Review were used—eg, “metabolic bone disease” or “inflammation” and “chronic kidney disease”, “chronic renal failure” or “chronic kidney disease” and “physiopathology”, “treatment”, “therapy”, “outcomes”, “morbidity”, or “mortality”. Randomised controlled trials or large observational studies on hard outcomes were retained by
ReviewClinical management of the uraemic syndrome in chronic kidney disease
Introduction
Kidney failure is associated with deterioration of body functions. The clinical picture as a whole—the uraemic syndrome—is named after urea, the most abundant metabolite retained in kidney failure and the first uraemic retention product identified. The uraemic syndrome can be caused by chronic kidney disease or acute kidney injury, and affects almost every organ system (panel 1).1 The syndrome results from the biological effects of metabolites that are not excreted or metabolised by the kidneys and are retained within the body.2 Such metabolites are named uraemic retention products, or uraemic toxins if they exert biological or toxic effects. The deterioration of renal endocrine function (production of erythropoietin, active vitamin D, or renin), the deregulation of kidney electrolyte homoeostasis, and functional alterations resulting from chronic kidney disease and its causes (eg, diabetes, autoimmune disorders) also contribute to the syndrome. The clinical picture worsens with kidney failure, with coma and death (end-stage kidney disease; table 1) the ultimate result if the patient is left untreated. However, since the 1940s, renal replacement therapies (dialysis or transplantation) have extended the life expectancy of patients with this potentially fatal condition.
Although dialysis and transplantation extend the life expectancy of patients with uraemia, mortality remains substantially higher than in age-matched populations with normal kidney function;3, 4 general and cardiovascular mortality tend to rise even before patients need dialysis.5, 6 In this Review, we discuss several therapeutic options to treat the consequences of the uraemic syndrome in chronic kidney disease, based on the pathophysiology of the uraemic syndrome and taking into account newly detected, pathological pathways.
Although we have followed the principles of evidence-based medicine as much as possible in this Review, much of the data cited are from observation studies. Randomised controlled trials in kidney disease are scarce,7 and many studies have had negative results.8 This fact is largely attributable to the complex and multifactorial nature of the disease, which makes it difficult to recruit large patient groups with uniform pathophysiological backgrounds. Additionally, because of multi-layered pathophysiology, the effect of therapeutic options that correct one aspect of disease (eg, hypercholesterolaemia) can be masked by the effect of other factors (eg, hypertension, fluid overload) on outcome measures.
Section snippets
Traditional and non-traditional risk factors
Cardiovascular and non-cardiovascular mortality contribute equally to the high mortality seen in people with chronic kidney disease.9 Socioeconomic and geographical factors, including access to therapy, explain the variable mortality in chronic kidney disease and end-stage kidney disease populations.10 Cardiovascular disease in patients with chronic kidney disease is characterised by immunity-driven inflammatory changes that cause vessel wall stiffening, arteriopathy, and cardiomyopathy leading
Uraemic retention products
Information about uraemic retention products has increased continuously in the past few decades. At least 150 uraemic retention products have been described so far,13, 14 and with developments in metabolomics and proteomics in the past decade, each new study has the potential to add dozens of new substances to this list. The idea that removal of one single solute would be sufficient to solve the problem of uraemic toxicity has long since been abandoned. By contrast, the notion that all these
Scope of Review
Since the pathophysiology of the uraemic syndrome affects the function of almost every organ (panel 1), this Review is restricted to elements for which relevant information is available and that imply specific therapeutic approaches. Definition of which pathophysiological events are directly caused by uraemic retention products and which, as a whole or in part, are caused by other aspects of kidney dysfunction is not always easy. We will summarise which elements are linked to uraemic retention
Management
The studies, guidelines, position statements, and reviews referred to in this section are summarised in the appendix. Treatment aimed at modifying risk factors will be discussed in broad terms independently of underlying intermediate mechanisms. Of note, positive interventions in the general population, could counterintuitively cause or amplify complications in chronic kidney disease. This section on management includes 56 original studies (appendix), of which only 35 (63%) are randomised
Conclusion
Patients with chronic kidney disease have complex pathophysiology for which the underlying mechanisms intertwine (appendix). Inflammation and disturbed bone homoeostasis in particular lead to complications and high and accelerated mortality. Management (appendix) cannot always be based on high-level evidence, because of difficulties in the recruitment of patients with sufficiently homogeneous background of primary disease, metabolic features, and response to the uraemic syndrome. Specific
Search strategy and selection criteria
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Metabolites Associated With Uremic Symptoms in Patients With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study
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2022, Experimental GerontologyCitation Excerpt :Our previous data and some other results showed that B cell population was decreased in the elderly CKD patients and patients with lower B cell counts had a higher risk of CVD mortality (Molina et al., 2018; Lin et al., 2020). In CKD patients, the uremic environment produces an inflammatory condition and overload that may lead to cardiac remodeling (Vanholder et al., 2016). However, the relationship between B cells and cardiac remodeling in advanced CKD patients has not been reported as far as we know.
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2021, Cardiology ClinicsCitation Excerpt :However, the negative side of this intervention is the risk of worsening existing malnutrition or systemic protein depletion, especially in frail patients and those with heavy proteinuria, in which case protein restriction might be less beneficial. In general, in patients with CKD who are not on dialysis or more than 3 months after transplantation, a protein intake of 0.6 to 0.8 g/kg/d is recommended.67 Modifying the composition or function of intestinal microbiota is another interesting option.
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