Rethinking an effective AV fistula-graft screening program. An "A B C".

The goal of a vascular access screening program is to detect and preemptively correct hemodynamically significant stenosis, however, a practice pattern allowing to implement such a program still remains to be defined. Achieving balance between the increase in access-related procedures by adopting an aggressive screening program, and the risks associated with the absence of any screening program, i.e., failure or abandonment of the arterio-venous access with need for central venous catheter placement, can be extremely challenging. All major guidelines agree about the role of arterio-venous access monitoring, but the way surveillance should be managed is still a controversial issue. Preserving long-term vascular access function should be a goal for all hemodialysis teams, yet it ideally requires a multidisciplinary effort with a monitoring program, calling for a great deal of involvement by hemodialysis health professionals. In this context, the engagement of skilled nurses and the role of patient empowerment with collaborative decision-making may be the key to a successful vascular access screening program. Screening programs should be personalized, shared with the patients, and tailored according to vascular access type and site. In the near future, new devices and the use of artificial intelligence may allow to support interpretation of complex data and lead to the development of prediction models for vascular access failure.

An Innovative Synbiotic Formulation Decreases Free Serum Indoxyl Sulfate, Small Intestine Permeability and Ameliorates Gastrointestinal Symptoms in a Randomized Pilot Trial in Stage IIIb-IV CKD Patients.

Proteolytic dysbiosis of the gut microbiota has been recognized as both a typical feature of chronic kidney disease (CKD) and a risk factor for its progression. Blood accumulation of gut-derived uremic toxins (UTs) like indoxyl sulfate (IS) and p-cresyl sulfate (PCS), intestinal permeability and constipation are typical features accompanying CKD progression and triggering chronic inflammation. In order to verify the efficacy of the innovative synbiotic formulation NATUREN G® in modulating the levels of circulating UTs, intestinal permeability and gastrointestinal symptoms, we set up a randomized, single-blind, placebo-controlled, pilot trial in stage IIIb-IV CKD patients and in healthy controls. Two-month administration of the synbiotic resulted in a decrease of free IS, as compared with the placebo-treated arm, only in the CKD group. The other UTs did not significantly change, although different trends in time (increase in the placebo arm and decrease in the synbiotic arm) were observed. Moreover, after supplementation, reduction of small intestinal permeability and amelioration of abdominal pain and constipation syndromes were observed only in the CKD group. The obtained results suggest the specificity of action of NATUREN G® in CKD and justify further validation in a wider study population.

[Nephrologists' role in a changing climate].

Human-induced climate changes represent an increasing concern in recent years. Among the medical specialties, Nephrology is the most interested in the negative effects of climate changes on human health. Kidneys in fact play a crucial role in blood volume regulation as well as in the extra- and intracellular osmolality that allow normal metabolism. Furthermore, urinary concentration minimizes fluid losses, while also insuring the excretion of nitrogenous wastes. The harmful effects of heat can lead to both acute and chronic kidney diseases, electrolyte abnormalities, kidney stone formation and urinary tract infections. As global warming increases, major efforts are required worldwide to assure adequate hydration and prevent overheating in vulnerable populations. While our activities make us responsible agents, there are also several opportunities to change the game, both individually and as a scientific society. This call to action intends to raise awareness on environmentally sustainable practices and encourage the nephrology community in Italy to participate in this important discussion.

AQP1-Containing Exosomes in Peritoneal Dialysis Effluent As Biomarker of Dialysis Efficiency.

The water channel Aquaporin 1 (AQP1) plays a fundamental role in water ultrafiltration during peritoneal dialysis (PD) and its reduced expression or function may be responsible for ultrafiltration failure (UFF). In humans, AQP1 is expressed in the endothelium of the peritoneal capillaries but its expression in mesothelial cells (MC) and its functional role in PD is still being debated. Here, we studied a cohort of 30 patients using PD in order to determine the presence of AQP1 in peritoneal biopsies, AQP1 release in the PD effluent through exosomes and the correlation of AQP1 abundance with the efficiency of peritoneal ultrafiltration. The experiments using immunofluorescence showed a strong expression of AQP1 in MCs. Immunoblotting analysis on vesicles isolated from PD effluents showed a consistent presence of AQP1, mesothelin and Alix and the absence of the CD31. Thus, this suggests that they have an exclusive mesothelial origin. The immunoTEM analysis showed a homogeneous population of nanovesicles and confirmed the immunoblotting results. Interestingly, the quantitative analysis by ELISA showed a positive correlation between AQP1 in the PD effluent and ultrafiltration (UF), free water transport (FWT) and Na-sieving. This evidence opens the discussion on the functional role of mesothelial AQP1 during PD and suggests that it may represent a potential non-invasive biomarker of peritoneal barrier integrity, with predictive potential of UFF in PD patients.

[The peritoneal ultrafiltration in patients with cardio-renal disease].

In Italy, the congestive heart failure is the leading cause of hospitalization and despite advances in therapy, the long-term prognosis is poor. Congestive heart failure is associated with advanced varying degrees of chronic renal disease that identify the cardio-renal syndrome type 2. High-dose diuretic therapy often fail to solve the water overload that is frequently the cause of death. The resistance to diuretics aggravates the state of the patient's edema and consequently morbidity and mortality. In the acute stage, the extracorporeal ultrafiltration unable to repair over hydration but needs frequent access weekly or midweek at the dialysis center. In addition, the significant changes of the fluid overload induce the risk of intradialytic hypotension and consequent renal hypoperfusion can cause a gradual loss of kidney function. The ultrafiltration can also be obtained using a method similar to the peritoneal dialysis (peritoneal ultrafiltration -PUF) but with a limited daily commitment both manual and automated modalities because the indication is not the correction of end stage renal disease. PUF is a home treatment and is indicated for chronic congestive heart failure with refractory hypervolemia despite optimal sequential diuretic therapy. PUF clinical results for the treatment of chronic congestive heart failure have demonstrated effectiveness in improving the clinical condition with reduction of NYHA class and improvement of FE%, the reduction of days of hospitalization, in reducing mortality, improving quality patient's life. In addition, PUF ensures a constant and continuous ultrafiltration, similar to renal function and thus allows a constant hemodynamic stability and ensures the maintenance of diuresis and the residual renal function. Therefore PUF in patients with refractory heart failure seems to be a viable integration of cardiological therapy and the encouraging results lead to the search of a multidisciplinary collaboration between cardiologist and nephrologist to ensure the patient a simple and effective "home" management for the treatment of a pathology so serious.