## 1 Introduction  
Chronic kidney disease (CKD) refers to damaged kidneys with decreased capability to filter blood. CKD can evolve into end-stage-renal disease (ESRD), where the kidneys do not work, necessitating dialysis [1, 2]. An altered kidney functionality determines an excess of waste metabolites that, accumulating in blood, causes other health problems, such as heart disease and stroke [3]. The incidence of CKD is growing worldwide, becoming a widely recognized problem for public health. The general increase in the average age of the population and the decrease in the mortality of patients at risk of renal failure are among the main factors linked to the increased incidence of CKD. Hence, due to the increasing costs for the management of CKD and ESRD patients, researchers are searching for alternative strategies to treat CKD patients. In the last years, increasing evidence has highlighted that a bidirectional relationship, defined as the renal-gut axis, exists between gut microbes and nephropathy [4; 5]. In CKD, renal damage determines an accumulation of urea and nitrogenous compounds in both blood and intestinal lumen [6]. Therefore, urea and its derivatives (i.e., ammonia and other nitrogenous compounds) cause significant deviations in the optimal pH range of the gut, and both urea and intestinal pH strongly favor the proliferation of proteolytic bacteria [7; 8]. From this point of view, the genomic potential of specific bacterial patterns (e.g., Proteobacteria and relative sub-taxa, such as _Enterobacteriaceae_) determines the production of secondary metabolites, starting from the overabundant nitrogen compounds found in the intestinal lumen of nephropathic subjects [8]. Those secondary metabolites, known as uremic toxins (e.g., trimethylamine-N-oxide, TMAO, indoxyl sulfate, IS, and \(p\)-cresyl sulfate (\(p\)CS)), cause a worsening of renal function and, therefore, the establishment of a vicious cycle along the renal-gut axis [9; 10]. In this context, some novel strategies to treat nephropathy are based on either nutritional therapy (e.g., low- or very-low-protein diets) [11; 12; 13] or the use of probiotics and prebiotics, alone or in combination (i.e., synbiotics) [14; 15; 16; 17]. The common aim of these alternative strategies is to reduce the typical dysbiosis and symptoms affecting subjects with low kidney functionality, shifting from the dominance of proteolytic gut microbiota to saccharolytic. These strategies also aim to delay ESRD onset and, thus, the need for dialysis. The shift from proteolytic to saccharolytic metabolism firstly leads to a reduction in the production and accumulation of uremic toxins. Additionally, the production of short-chain fatty acids (SCFAs) by saccharolytic bacteria has also been largely recognized as beneficial [18; 19] in CKD patients [17; 20; 21]. Nowadays, a large body of evidence is available about the effects caused by the administration of probiotics and synbiotics to CKD patients [22; 23; 24; 25; 26]. The framework of symptomatology linked to CKD is widely recognized, and bacterial patterns and relative metabolites that mark the nephropathy are known. However, one of the major limitations of innovative formulations is the minimal evidence for their efficacy under specific conditions before being applied in vivo. In some cases, probiotics may not be able to survive in specific conditions and/or environments. Consequently, in our opinion, it is necessary to start from in vitro evaluations that simulate the conditions encountered by probiotics and synbiotics used for treating CKD. Therefore, before proceeding with in vivo evaluation, and to develop an innovative symbiotic with a prospective application in CKD patients, we aimed to select the best combination between probiotics, prebiotics, and antioxidants from vegetables and vegetable extracts.