Numerous studies have indicated that the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD) is strictly associated with the accumulation of toxic metabolites in blood and other metabolic compartments. This accumulation was suggested to be related to enhanced generation of toxins from the dysbiotic microbiome accompanied by their reduced elimination by impaired kidneys. Intestinal microbiota play a key role in the accumulation of uremic toxins due to the fact that numerous uremic solutes are generated in the process of protein fermentation by colonic microbiota. Some disease states, including CKD, are associated with the presence of dysbiosis, which can be defined as an “imbalanced intestinal microbial community with quantitative and qualitative changes in the composition and metabolic activities of the gut microbiota”. The results of studies have confirmed the altered composition and functions of gut microbial community in chronic kidney disease. In the course of CKD protein-bound uremic toxins, including indoxyl sulfate, p-cresyl glucuronide, p-cresyl sulfate and indole-3-acetic acid are progressively accumulated. The presence of chronic kidney disease may be accompanied by the development of intestinal inflammation and epithelial barrier impairment leading to hastened systemic translocation of bacterial-derived uremic toxins and consequent oxidative stress injury to the kidney, cardiovascular and endocrine systems. These findings offer new therapeutic possibilities for the management of uremia, inflammation and kidney disease progression and the prevention of adverse outcomes in CKD patients. It seems that dietary interventions comprising prebiotics, probiotics, and synbiotics could pose a promising strategy in the management of uremic toxins in CKD.
Chronic kidney disease is highly prevalent worldwide. The decline of renal function is associated with inadequate removal of a variety of uremic toxins that exert detrimental effects on cells functioning, thus affecting the cardiovascular system. The occurrence of cardiovascular aberrations in CKD is related to the impact of traditional risk factors and non-traditional CKD-associated risk factors, including anemia; inflammation; oxidative stress; the presence of some uremic toxins; and factors related to the type, frequency of dialysis and the composition of dialysis fluid. Cardiovascular diseases are the most frequent cause for the deaths of patients with all stages of renal failure. The kidney is one of the vital sources of antioxidant enzymes, therefore, the impairment of this organ is associated with decreased levels of these enzymes as well as increased levels of pro-oxidants. Uremic toxins have been shown to play a vital role in the onset of oxidative stress. Hemodialysis itself also enhances oxidative stress. Elevated oxidative stress has been demonstrated to be strictly related to kidney and cardiac damage as it aggravates kidney dysfunction and induces cardiac hypertrophy. Antioxidant therapies may prove to be beneficial since they can decrease oxidative stress, reduce uremic cardiovascular toxicity and improve survival.
High-density lipoproteins comprise roughly 25–30% of the circulating proteins involved in the transport of lipids in circulation. These particles differ in size and lipid composition. Recent evidence suggests that the quality of HDL particles (which depends on shape, size and the composition of proteins and lipids determining HDL functionality) may be more important than their quantity. The functionality of HDL is mirrored by its cholesterol efflux activity, as well as its antioxidant (including the protection of LDL against oxidation), anti-inflammatory and antithrombotic properties. The results of many studies and meta-analyses imply the beneficial impact of aerobic exercise on HDL-C levels. Physical activity was found to be usually associated with an increase in HDL cholesterol and a decrease in LDL cholesterol and triglycerides. Exercise, apart from inducing quantitative alterations in serum lipids, exerts a beneficial impact on HDL particle maturation, composition and functionality. The Physical Activity Guidelines Advisory Committee Report underlined the importance of establishing a program recommending exercises that enable attainment of maximal advantage at the lowest level of risk. The aim of this manuscript is to review the impact of different types of aerobic exercise (various intensities and durations) on the level and quality of HDL.
The specific interest concerning HDL cholesterol (HDL-C) is related to its ability to uptake and return surplus cholesterol from peripheral tissues back to the liver and, therefore, to its role in the prevention of cardiovascular diseases, such as atherosclerosis and myocardial infarction, but also transient ischemic attack and stroke. Previous epidemiological studies have indicated that HDL-C concentration is inversely associated with the risk of cardiovascular disease and that it can be used for risk prediction. Some genetic disorders are characterized by markedly elevated levels of HDL-C; however, they do not translate into diminished cardiovascular risk. The search of the potential causative relationship between HDL-C and adverse events has shifted the attention of researchers towards the composition and function of the HDL molecule/subfractions. HDL possesses various cardioprotective properties. However, currently, it appears that higher HDL-C is not necessarily protective against cardiovascular disease, but it can even be harmful in extremely high quantities.
An increasing number of evidence indicates that metabolic factors may play an important role in the development and progression of certain types of cancers, including renal cell carcinoma (RCC). This tumour is the most common kidney cancer which accounts for approximately 3–5% of malignant tumours in adults. Numerous studies indicated that concomitant diseases, including diabetes mellitus (DM) and hypertension, as well as obesity, insulin resistance, and lipid disorders, may also influence the prognosis and cancer-specific overall survival. However, the results of studies concerning the impact of metabolic factors on RCC are controversial. It appears that obesity increases the risk of RCC development; however, it may be a favourable factor in terms of prognosis. Obesity is closely related to insulin resistance and the development of diabetes mellitus type 2 (DM2T) since the adipocytes in visceral tissue secrete substances responsible for insulin resistance, e.g., free fatty acids. Interactions between insulin and insulin-like growth factor (IGF) system appear to be of key importance in the development and progression of RCC; however, the exact role of insulin and IGFs in RCC pathophysiology remains elusive. Studies indicated that diabetes increased the risk of RCC, but it might not alter cancer-related survival. The risk associated with a lipid profile is most mysterious, as numerous studies provided conflicting results. Even though large studies unravelling pathomechanisms involved in cancer growth are required to finally establish the impact of metabolic factors on the development, progression, and prognosis of renal cancers, it seems that the monitoring of health conditions, such as diabetes, low body mass index (BMI), and lipid disorders is of high importance in clear-cell RCC.
Renal cell carcinomas (RCCs) is a group of various malignant tumours of the renal cortex displaying distinct clinical, morphologic, and genetic features. Clear cell papillary renal cell carcinoma (ccpRCC), belonging to this group, shares morphologic features with both clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) and therefore, more strict diagnostic criteria should be developed to avoid misdiagnosis. Despite overlapping features, ccpRCC has also distinct clinical behaviour, histologic characteristics (morphologic and immunohistochemical), and genomic features. The concepts concerning this tumour are constantly developing since its biological potential and molecular basis remains to be fully unravelled. First reports indicated the presence of ccpRCC in end-stage renal disease, and they underlined the enriched development in this group of patients; however, currently, it is known that such tumours can also occur spontaneously in the normal kidney. Numerous studies have demonstrated that clinical outcomes and prognosis of ccpRCC patients is highly favourable. Till now, no convincing evidence of metastatic ccpRCC or death caused by the disease has been found. Therefore, it is of high importance to correctly differentiate ccpRCC from other subtypes of RCC with a much worse prognosis and to introduce appropriate management.
Cancers are a frequent cause of morbidity and mortality. There are many risk factors for tumours, including advanced age, personal or family history of cancer, some types of viral infections, exposure to radiation and some chemicals, smoking and alcohol consumption, as well as obesity. Increasing evidence suggest the role of obesity in the initiation and progression of various cancers, including renal cell carcinoma. Since tumours require energy for their uncontrollable growth, it appears plausible that their initiation and development is associated with the dysregulation of cells metabolism. Thus, any state characterised by an intake of excessive energy and nutrients may favour the development of various cancers. There are many factors that promote the development of renal cell carcinoma, including hypoxia, inflammation, insulin resistance, excessive adipose tissue and adipokines and others. There are also many obesity-related alterations in genes expression, including DNA methylation, single nucleotide polymorphisms, histone modification and miRNAs that can promote renal carcinogenesis. This review focuses on the impact of obesity on the risk of renal cancers development, their aggressiveness and patients’ survival.
Cardiovascular disease (CAD) is the main cause of morbidity and deaths in the western world. The development of atherosclerosis underlying CAD development begins early in human life. There are numerous genetic and environmental risk factors accelerating its progression which then leads to the occurrence of acute events. Despite considerable progress in determining risk factors, there is still a lot of work ahead since identified determinants are responsible only for a part of overall CAD risk. Current therapies are insufficient to successfully reduce the risk of atherosclerosis development. Therefore, there is a need for effective preventive measures of clinical manifestations of atherosclerosis since the currently available drugs cannot prevent the occurrence of even 70% of clinical events. The shift of the target from lipid metabolism has opened the door to many new therapeutic targets. Currently, the majority of known targets for anti-atherosclerotic drugs focus also on inflammation (a common mediator of many risk factors), mechanisms of innate and adaptive immunity in atherosclerosis, molecule scavengers, etc. The therapeutic potential of cyclodextrins, protein kinase inhibitors, colchicine, inhibitors of p38 mitogen-activated protein kinase (MAPK), lipid dicarbonyl scavengers, a monoclonal antibody targeting interleukin-1β, and P-selectin inhibitors is still not fully confirmed and requires confirmation in large clinical trials. The preliminary results look promising.
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