Urea at post-dialysis levels induces increased ROS in a number of cell types. The aim of this study was to determine whether urea-induced production of ROS remains elevated after urea is no longer present, and, if it does, to characterize its origin and effects. Human arterial endothelial cells were incubated with 20 mM urea for two days, and then cells were incubated for an additional two days in medium alone. Maximal ROS levels induced by initial urea continued at the same level despite urea being absent. These effects were prevented by either MnSOD expression or by Nox1/4 inhibition with GKT13781. Sustained urea-induced ROS caused a persistent reduction in mtDNA copy number and electron transport chain transcripts, a reduction in transcription of mitochondrial fusion proteins, an increase in mitochondrial fission proteins, and persistent expression of endothelial inflammatory markers. The SOD-catalase mimetic MnTBAP reversed each of these. These results suggest that persistent increases in ROS after cells are no long exposed to urea may play a major role in continued kidney damage and functional decline despite reduction of urea levels after dialysis.

Chronic kidney disease is a significant global health burden and a leading cause of cardiovascular morbidity and mortality. Diabetes mellitus is the primary cause of kidney disease, driving the progression of both micro- and macrovascular complications. Sustained hyperglycemia initiates a cascade of deleterious molecular and cellular events, including mitochondrial dysfunction, inflammation, oxidative stress, and dysregulated apoptosis and autophagy, which collectively contribute to the progression of renal injury. Beyond these well-established mechanisms, a compelling body of evidence highlights the pivotal role of epigenetic alterations (such as DNA methylation, histone post-translational modifications, and non-coding RNAs) in mediated long-term kidney damage. The interplay between transcriptional and epigenetic regulation underlies the phenomenon of the “metabolic memory”, wherein cellular dysfunction persists even after glycemic control is achieved. This review synthesizes the current knowledge on mechanisms sustaining metabolic and epigenetic memory, with a particular focus on the epigenetic machinery that establishes and maintains these signals, a concept increasingly termed “epigenetic memory.” Given their reversible nature, epigenetic determinants are emerging as promising biomarkers and a compelling therapeutic avenue. Targeting these “epifactors” offers a novel strategy to halt progression to end-stage renal disease, thereby paving the way for precision medicine approaches in diabetes-related renal disease.

Chronic kidney disease in children is an irreversible process that may lead to end-stage renal disease. The mortality rate in children with end-stage renal disease who receive dialysis increased dramatically in the last decade, and it is significantly higher compared with the general pediatric population. Furthermore, dialysis and transplant patients, who have developed end-stage renal disease during childhood, live respectively far less as compared with age/race-matched populations. Different reports show that cardiovascular disease is the leading cause of death in children with end-stage renal disease and in adults with childhood-onset chronic kidney disease, and that children with chronic kidney disease are in the highest risk group for the development of cardiovascular disease. Urea, which is generated in the liver during catabolism of amino acids and other nitrogenous metabolites, is normally excreted into the urine by the kidneys as rapidly as it is produced. When renal function is impaired, increasing concentrations of blood urea will steadily accumulate. For a long time, urea has been considered to have negligible toxicity. However, the finding that plasma urea is the only significant predictor of aortic plaque area fraction in an animal model of chronic renal failure -accelerated atherosclerosis, suggests that the high levels of urea found in chronic dialysis patients might play an important role in accelerated atherosclerosis in this group of patients. The aim of this review was to provide novel insights into the role played by urea in the pathogenesis of accelerated cardiovascular disease in renal failure.

Consumers’ conviction of the benefits of probiotics is influenced by their existing beliefs and by the information they receive from healthcare professionals. The attitude of healthcare professionals towards commercially available probiotics will, therefore, determine how trustworthy and beneficial these products are perceived by consumers. Furthermore, due to European Union legislation, companies are prohibited from displaying information on product packaging; therefore, consumers are dependent primarily on healthcare professionals for correct information and guidance on the use of these products. The aim of this pilot study was to explore the understanding and use of probiotics in clinical practice by professionals who are involved in child healthcare in different European countries and to assess how much they value the scientific evidence behind these products. The study was performed using a cross-sectional, descriptive, 30-question online questionnaire circulated among healthcare professionals belonging to three professional categories that are typically involved in childhood probiotic prescription: paediatricians, dieticians and general practitioners. The questionnaire was developed using web-based standard guidelines, and the questions were modelled on those used in previously published probiotics studies. Overall, 27,287 healthcare professionals belonging to three major European scientific societies were contacted by the organizations participating in the study. In total, 1360 valid questionnaires were recorded, and the results were statistically analysed. The results emphasize the importance for healthcare professionals to be properly educated and updated on probiotics. An improved knowledge about probiotics led to increased prescriptive confidence. To disseminate accurate information on probiotics, healthcare professionals look for appropriate and scientifically validated educational platforms to acquire information, explore concerns and barriers and look for positive approaches towards recommending probiotics.