Advanced glycation end-products (AGEs) are an assorted group of molecules formed through covalent bonds between a reduced sugar and a free amino group of proteins, lipids, and nucleic acids. Glycation alters their structure and function, leading to impaired cell function. They can be originated by physiological processes, when not counterbalanced by detoxification mechanisms, or derive from exogenous sources such as food, cigarette smoke, and air pollution. Their accumulation increases inflammation and oxidative stress through the activation of various mechanisms mainly triggered by binding to their receptors (RAGE). So far, the pathogenic role of AGEs has been evidenced in inflammatory and chronic diseases such as chronic kidney disease, cardiovascular disease, and diabetic nephropathy. This review focuses on the AGE-induced kidney damage, by describing the molecular players involved and investigating its link to the excess of body weight and visceral fat, hallmarks of obesity. Research regarding interventions to reduce AGE accumulation has been of great interest and a nutraceutical approach that would help fighting chronic diseases could be a very useful tool for patients’ everyday lives.

Due to the involvement of the endocannabinoid system (ECS) in cancer onset and progression and the less studied connection between ECS and bladder cancer, here an evaluation of the ECS modifications associated with bladder cancer is reported. Urine samples were collected from healthy volunteers and patients with bladder cancer at different grades. Endocannabinoids (ECs) and N-acylethanolamides (NAEs) were quantified by HPLC-MS/MS and results normalized for creatinine content. An increase in the urine concentrations of four ECs and NAEs analyzed was observed with a statistically significant increase in the arachidonoylethanolamide (AEA) and stearoylethanoamide (SEA) associated with bladder cancer. Receiver operating characteristic curves built with AEA and SEA data allowed the selection of 160 pg/mL for SEA (area under the curve (AUC) = 0.91, Selectivity (SE) 94%, Specificity (SP) 45%) and 8 pg/mL for AEA (AUC = 0.85, SE 94%, SP 61%) as the best cut-off values. Moreover, data from bladder cancer samples at different grades were derived from The Cancer Genome Atlas, and the expressions of thirteen different components of the “endocannabinoidome” were analyzed. Statistical analysis highlights significant variations in the expression of three enzymes involved in EC and NAE turnover in bladder cancer.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common events after radical nephrectomy (RN). In this study we aimed to predict AKI and CKD after RN relying on specific histological aspects. We collected data from a cohort of 144 patients who underwent radical nephrectomy. A histopathological review of the healthy part of the removed kidney was performed using an established chronicity score (CS). Logistic regression analyses were performed to predict AKI after RN, while linear regression analysis was adopted for estimated glomerular filtration rate (eGFR) variation at 1 year. The outcomes of the study were to determine variables correlated with AKI onset, and with eGFR decay at 1 year. The proportion of AKI was 64%. Logistic analyses showed that baseline eGFR independently predicted AKI (odds ratio 1.04, 95%CI 1.02:1.06). Moreover, AKI (Beta −16, 95%CI −21:−11), baseline eGFR (Beta −0.42, 95%CI −0.52:−0.33), and the presence of arterial narrowing (Beta 10, 95%CI 4:15) were independently associated with eGFR decline. Our findings showed that AKI onset and eGFR decline were more likely to occur with higher baseline eGFR and lower CS, highlighting that RN in normal renal function patients represents a more traumatic event than its CKD counterpart.

Warm renal ischemia performed during partial nephrectomy has been found to be associated with kidney disease. Since endogenous ouabain (EO) is a neuro-endocrine hormone involved in renal damage, we evaluated the role of EO in renal ischemia-reperfusion injury (IRI). We measured plasma and renal EO variations and markers of glomerular and tubular damage (nephrin, KIM-1, Kidney-Injury-Molecule-1, α1 Na-K ATPase) and the protective effect of the ouabain inhibitor, rostafuroxin. We studied five groups of rats: (1) normal; (2) infused for eight weeks with ouabain (30 µg/kg/day, OHR) or (3) saline; (4) ouabain; or (5) saline-infused rats orally treated with 100 µg/kg/day rostafuroxin for four weeks. In group 1, 2–3 h after IRI, EO increased in ischemic kidneys while decreased in plasma. Nephrin progressively decreased and KIM-1 mRNA increased starting from 24 h. Ouabain infusion (group 2) increased blood pressure (from 111.7 to 153.4 mmHg) and ouabain levels in plasma and kidneys. In OHR ischemic kidneys at 120 h from IRI, nephrin, and KIM-1 changes were greater than those detected in the controls infused with saline (group 3). All these changes were blunted by rostafuroxin treatment (groups 4 and 5). These findings support the role of EO in IRI and suggest that rostafuroxin pre-treatment of patients before partial nephrectomy with warm ischemia may reduce IRI, particularly in those with high EO.

Preoperative nutritional status is a pivotal aspect to consider in patients with cancer undergoing radical cystectomy (RC), as those at risk of malnutrition or already malnourished are more prone to post-surgical complications. The loss of muscle mass is a major consequence of cancer-related malnutrition. It is associated with increased risk of hospital readmission, longer hospitalization, and higher mortality. Nowadays, the close relationship between nutritional and immunological aspects under stressful conditions, such as surgery, represents an emerging scientific and clinical issue. Indeed, the synergistic action of reduced food intake and systemic inflammation generates metabolic derangements with tissue catabolism, including skeletal muscle breakdown, which is, in turn, associated with immune system dysfunction. In order to offer an additional immune-nutritional boost to the post-surgical phase, particularly in malnourished patients, nutritional support may include oral nutritional supplements and/or enteral formulas enriched with specific nutrients such as omega-3 fatty acids, arginine, glutamine, and nucleotides, with acknowledged immune-modulating effects. In the present narrative review, we addressed the state of the art of the available scientific literature on the benefit of immunonutrition in patients undergoing RC for cancer and suggest possible future perspectives to be explored. Although the role of immunonutrition was found to be little explored in the context of urologic oncology, the preliminary available data on radical cystectomy, summarized in the present paper, are promising and suggest that it may improve postoperative outcomes through immunomodulation, regardless of nutritional status before surgery.