The vascular endothelium is a dynamic, functionally complex organ, modulating multiple biological processes, including vascular tone and permeability, inflammatory responses, thrombosis, and angiogenesis. Endothelial dysfunction is a threat to the integrity of the vascular system, and it is pivotal in the pathogenesis of atherosclerosis and cardiovascular disease. Reduced nitric oxide (NO) bioavailability is a hallmark of chronic kidney disease (CKD), with this disturbance being almost universal in patients who reach the most advanced phase of CKD, end-stage kidney disease (ESKD). Low NO bioavailability in CKD depends on several mechanisms affecting the expression and the activity of endothelial NO synthase (eNOS). Accumulation of endogenous inhibitors of eNOS, inflammation and oxidative stress, advanced glycosylation products (AGEs), bone mineral balance disorders encompassing hyperphosphatemia, high levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23), and low levels of the active form of vitamin D (1,25 vitamin D) and the anti-ageing vasculoprotective factor Klotho all impinge upon NO bioavailability and are critical to endothelial dysfunction in CKD. Wide-ranging multivariate interventions are needed to counter endothelial dysfunction in CKD, an alteration triggering arterial disease and cardiovascular complications in this high-risk population.

Chronic kidney disease (CKD) is a condition characterized by the gradual loss of kidney function over time and it is a worldwide health issue. The estimated frequency of CKD is 10% of the world’s population, but it varies greatly on a global scale. In absolute terms, the staggering number of subjects affected by various degrees of CKD is 850,000,000, and 85% of them are in low- to middle-income countries. The most important risk factors for chronic kidney disease are age, arterial hypertension, diabetes, obesity, proteinuria, dyslipidemia, and environmental risk factors such as dietary salt intake and a more recently investigated agent: pollution. In this narrative review, we will focus by choice just on some risk factors such as age, which is the most important non-modifiable risk factor, and among modifiable risk factors, we will focus on hypertension, salt intake, obesity, and sympathetic overactivity.

The Italian Society of Nephrology has tasked its Working Group on Physical Exercise with developing a consensus statement document on physical activity and exercise in patients with chronic kidney disease (CKD). This paper consists of 16 points that were discussed, and approved using the mini-Delphi method by 15 members of the working group. Each statement is based on a comprehensive review of the literature, clinical experience, and expert opinions. Overall, the statements affirm that regular physical activity and exercise training offer numerous benefits to CKD patients, including improved physical function, enhanced cardiometabolic and neuromuscular function, cognitive benefits, and an overall improvement in quality of life. Furthermore, exercise may provide nephroprotection and reduce mortality. These advantages are observed across all CKD stages, whether on conservative therapy or kidney replacement therapy (hemodialysis or peritoneal dialysis), and in kidney transplant recipients. Moreover, when physical activity and exercise training are implemented with appropriate precautions, they are safe in CKD patients. Gradual physical activity and customized exercise programs should be tailored to the patient's exercise tolerance, potentially enhancing compliance. Clinicians are encouraged to use a series of questionnaires and tests to assess the patient's level of physical activity and performance. However, exercise and physical activity are poorly implemented in clinical practice due to many barriers related to patients and healthcare staff. Overcoming these barriers requires the proactive role of the nephrologists, who should actively incorporate exercise training and promote physical activity within routine care plans. Adopting a multidisciplinary team approach, which includes nephrologists, nurses, exercise professionals, and dietitians, is crucial for providing comprehensive rehabilitation for CKD patients. Integrating new technologies and remote check ups could further enhance the effectiveness of these interventions. Graphical abstract

Older adults dialysis patients represent the frailest subgroup of the End Stage Renal Disease (ESRD) population and physical exercise program may mitigate the age-related decline in muscle mass and function. Dialysis patients of the EXCITE trial aged > 65 years (n = 115, active arm, n = 53; control arm, n = 62) were submitted in random order to a home based, low intensity physical exercise program. At baseline and 6 months after exercise training 6-min walking distance (6MWD) and 5-time sit-to-stand test (5STS) were performed, and quality of life (QoL) was tested. The training program improved both the 6MWD (6-months: 327 ± 86 m versus baseline: 294 ± 74 m; P < 0.001) and the 5STS time (6-months: 19.8 ± 5.6 s versus baseline: 22.5 ± 5.1 s; P < 0.001) in the exercise group whereas they did not change in the control group (P = 0.98 and 0.25, respectively). The between-arms differences (6 months-baseline) in the 6MWD (+ 34.0 m, 95% CI: 14.4 to 53.5 m) and in the 5STS time changes (− 1.9 s, 95% CI: -3.6 to − 0.3 s) were both statistically significant (P = 0.001 and P = 0.024, respectively). The cognitive function dimension of QoL significantly reduced in the control arm (P = 0.04) while it remained unchanged in the active arm (P = 0.78) (between groups difference P = 0.05). No patient died during the trial and the training program was well tolerated. This secondary analysis of the EXCITE trial shows that a home-based, exercise program improves physical performance and is well tolerated in elderly ESRD patients. The trial was registered in ClinicalTrials.Gov ( Clinicaltrials.gov identifier: NCT01255969) on December 8, 2010.

Obesity is a worldwide epidemic and there is compelling evidence that excess fat is closely associated with chronic kidney disease (CKD) and end-stage kidney failure. In this review, we will describe some important mechanisms related with the pathogenesis and treatment of CKD in obesity by emphasizing the role of excess fat in renal haemodynamic and structural alterations.