Institute of Fundamental Technological Research

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, uremic toxins, gut microbiota, cardiovascular risk

Anincreasing number of evidence indicates that metabolic factorsmayplay an important role in the evelopment 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 carcinoma, obesity, insulin resistance, diabetes mellitus, lipid disorders