Home hemodialysis treatment and outcomes: retrospective analysis of the Knowledge to Improve Home Dialysis Network in Europe (KIHDNEy) cohort.

BACKGROUND: Utilization of home hemodialysis (HHD) is low in Europe. The Knowledge to Improve Home Dialysis Network in Europe (KIHDNEy) is a multi-center study of HHD patients who have used a transportable hemodialysis machine that employs a low volume of lactate-buffered, ultrapure dialysate per session. In this retrospective cohort analysis, we describe patient factors, HHD prescription factors, and biochemistry and medication use during the first 6 months of HHD and rates of clinical outcomes thereafter. METHODS: Using a standardized digital form, we recorded data from 7 centers in 4 Western European countries. We retained patients who completed ≥6 months of HHD. We summarized patient and HHD prescription factors with descriptive statistics and used mixed modeling to assess trends in biochemistry and medication use. We also estimated long-term rates of kidney transplant and death. RESULTS: We identified 129 HHD patients; 104 (81%) were followed for ≥6 months. Mean age was 49 years and 66% were male. Over 70% of patients were prescribed 6 sessions per week, and the mean treatment duration was 15.0 h per week. Median HHD training duration was 2.5 weeks. Mean standard Kt/Vurea was nearly 2.7 at months 3 and 6. Pre-dialysis biochemistry was generally stable. Between baseline and month 6, mean serum bicarbonate increased from 23.1 to 24.1 mmol/L (P = 0.01), mean serum albumin increased from 36.8 to 37.8 g/L (P = 0.03), mean serum C-reactive protein increased from 7.3 to 12.4 mg/L (P = 0.05), and mean serum potassium decreased from 4.80 to 4.59 mmol/L (P = 0.01). Regarding medication use, the mean number of antihypertensive medications fell from 1.46 agents per day at HHD initiation to 1.01 agents per day at 6 months (P < 0.001), but phosphate binder use and erythropoiesis-stimulating agent dose were stable. Long-term rates of kidney transplant and death were 15.3 and 5.4 events per 100 patient-years, respectively. CONCLUSIONS: Intensive HHD with low-flow dialysate delivers adequate urea clearance and good biochemical outcomes in Western European patients. Intensive HHD coincided with a large decrease in antihypertensive medication use. With relatively rapid training, HHD should be considered in more patients.

Neutrophil-dependent pentraxin-3 and reactive oxygen species production modulate endothelial dysfunction in haemodialysis patients.

BACKGROUND: The aim of this study was to investigate neutrophil activation and its role in long pentraxin-3 (PTX3) release and oxidative stress generation during haemodialysis (HD) and to correlate neutrophil PTX3 and oxidant expression with endothelial dysfunction. METHODS: Forty-seven uraemic patients on stable HD, 12 healthy subjects and 15 patients with congestive heart failure (New York Heart Association classes III and IV) were enrolled. Neutrophil PTX3 protein expression was evaluated by confocal microscopy. l -selectin expression, intracellular PTX3 localization and reactive oxygen species (ROS) generation in human neutrophils were measured by flow cytometry. NADPH-dependent superoxide generation was investigated by chemiluminescence. PTX3 plasma concentrations were measured by ELISA. Endothelial dysfunction was studied by flow-mediated dilation (FMD). RESULTS: The low baseline levels of FMD significantly improved after HD, but worsened by 24 h. A significant up-regulation of PTX3 protein expression, localized within secondary granules, was detected in neutrophils isolated at 30 and 240 min of HD, along with an increase in l -selectin expression. The up-regulation in intracellular PTX3 in neutrophils was associated with a significant increase in PTX3 plasma concentrations at 240 min. HD increased ROS production and NADPH oxidase activity in neutrophils. In a univariate analysis, pre-treatment with FMD was inversely correlated with PTX3 expression and ROS generation in neutrophils. In a multivariate analysis, both circulating pre-HD PTX3 and intracellular ROS generation by neutrophils were independent predictors of abnormal FMD. CONCLUSIONS: Neutrophil overexpression of PTX3 is associated with ROS overproduction and endothelial dysfunction and may represent an emerging marker of vascular damage progression in HD patients.

Effect of an L-carnitine-containing peritoneal dialysate on insulin sensitivity in patients treated with CAPD: a 4-month, prospective, multicenter randomized trial.

BACKGROUND: In peritoneal dialysis, the high glucose load absorbed from dialysis fluid contributes to several metabolic abnormalities, including insulin resistance. We evaluate the efficacy of a peritoneal dialysis solution containing l-carnitine as an additive to improve insulin sensitivity. STUDY DESIGN: Multicenter parallel randomized controlled trial. SETTING & PARTICIPANTS: Nondiabetic uremic patients on continuous ambulatory peritoneal dialysis enrolled in 8 peritoneal dialysis centers. INTERVENTION: Patients were randomly assigned to receive peritoneal dialysis diurnal exchanges with either a standard glucose-based solution (1.5% or 2.5% according to the patient's need) or a glucose-based solution (identical glucose amount) enriched with l-carnitine (0.1%, weight/volume; 2 g/bag) for 4 months, the nocturnal exchange with icodextrin being unmodified. OUTCOMES & MEASUREMENTS: The primary outcome was insulin sensitivity, measured by the magnitude of change from baseline in glucose infusion rate (in milligrams per kilogram of body weight per minute) during a euglycemic hyperinsulinemic clamp. Secondary outcomes were safety and tolerability, body fluid management, peritoneal dialysis efficiency parameters, and biochemistry tests. RESULTS: 35 patients were randomly assigned, whereas 27 patients (standard solution, n=12; experimental solution, n = 15) were analyzed. Adverse events were not attributable to treatment. Glucose infusion rates in the l-carnitine-treated group increased from 3.8 ± 2.0 (SD) mg/kg/min at baseline to 5.0 ± 2.2 mg/kg/min at day 120 (P = 0.03) compared with 4.8 ± 2.4 mg/kg/min at baseline and 4.7 ± 2.4 mg/kg/min at day 120 observed in the control group (P = 0.8). The difference in glucose infusion rates between groups was 1.3 (95% CI, 0.0-2.6) mg/kg/min. In patients treated with l-carnitine-containing solution, urine volume did not change significantly (P = 0.1) compared to a significant diuresis reduction found in the other group (P = 0.02). For peritoneal function, no differences were observed during the observation period. LIMITATIONS: Small sample size. CONCLUSIONS: The use of l-carnitine in dialysis solutions may represent a new approach to improving insulin sensitivity in nondiabetic peritoneal dialysis patients.

[Peritoneal dialysis: a time-limited therapy because of encapsulating peritoneal sclerosis? No, but due attention is warranted]. / Dialisi peritoneale: metodica a termine a causa della peritonite sclerosante? No, ma attenti!

Encapsulating peritoneal sclerosis (EPS) is a rare complication that occurs mainly in patients on long-term peritoneal dialysis (PD). It is characterized by marked thickening of the peritoneal membrane with signs of inflammation. Vascular occlusions and microscopic and macroscopic calcifications are frequent. Signs of acute and chronic inflammation are always present with leukocyte infiltration, microabscesses and giant cells of macrophage origin. The triggering factor in patients on PD may be an acute inflammatory process such as an episode of severe peritonitis. After discontinuation of PD for kidney transplant, immunosuppressive therapy with calcineurin inhibitors, which have profibrotic properties, may lead to EPS. After a switch from PD to hemodialysis, EPS may be induced by the inability to remove proinflammatory factors, cytokines, coagulation factors and fibrin from the peritoneal cavity. These considerations are not meant to imply a PD ''expiry date'' but should prompt nephrologists to be more careful in treating PD patients, using more biocompatible solutions and monitoring (through clinical observation and diagnostic evaluation) patients on long-term PD to avoid the appearance of this rare but dreaded complication.

Efficacy of Divinylbenzenic Resin in Removing Indoxyl Sulfate and P-Cresol Sulfate in Hemodialysis Patients: Results From an In Vitro Study and An In Vivo Pilot Trial (xuanro4-Nature 3.2).

High serum levels of microbiota-derived uremic toxins, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), are associated with chronic kidney disease (CKD) progression and cardiovascular complications. IS and PCS cannot be efficiently removed by conventional hemodialysis (HD), due to their high binding affinity for albumin. This study evaluates the efficacy of a divinylbenzene-polyvinylpyrrolidone (DVB-PVP) cartridge and a synbiotic to reduce uremic toxins in HD patients. First, the in vitro efficacy of DVB-PVP in adsorbing IS and PCS was evaluated. Second, a randomized, placebo-controlled pilot study in HD patients was carried out to establish whether the administration of a synbiotic, either individually and in association with DVB-PVP-HD, could reduce the production of uremic toxins. In vitro data showed that DVB-PVP resin removed a mean of 56% PCS and around 54% IS, after 6 h of perfusion. While, in the in vivo study, the DVB-PVP cartridge showed its adsorbing efficacy only for IS plasma levels. The combination of synbiotic treatment with DVB-PVP HD decreased IS and PCS both at pre- and post-dialysis levels. In conclusion, this study provides the first line of evidence on the synergistic action of gut microbiota modulation and an innovative absorption-based approach in HD patients, aimed at reducing plasma levels of IS and PCS.

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.

[Peritoneal Dialysis in Italy: the fourth GSDP-SIN census 2012].

OBJECTIVE: To know PD modalities and results in Italy. METHODS: The Census was carried out by means of an on-line questionnaire in all the 224 non-pediatric public centers which performed PD in 2012. The results were compared with those of previous Censuses. RESULTS: Incidence. In 2012 PD was begun (first treatment for ESRD) by 1,433 pts (CAPD: 54.3%) and HD by 4,700 pts (%PD-incidence= Cs-12: 23.4%; Cs-10: 23.3%; Cs-08: 22.8%; Cs-05: 24.2%; p=NS), with a further increase in incremental PD (Cs-12: 28.8%; Cs-10: 22.8%; Cs-08: 18.3%; Cs-05: 11.9%; p-0.001). Prevalence. At 31/12/12 there were 4,299 patients on PD (CAPD: 46.1%) (%PD-prevalence= Cs-12: 17.1%; Cs-10: 16.6%; Cs-08: 16.7%; Cs-05:16.8%; p=NS), 24.5% of whom were on assisted PD (family members: 82.3%; paid caregivers: 12.4%; nurses: 0.7%; NH: 3.0%). Out. In 2012 there was no change in the PD drop-out rate (30.9 ep/100yrs-pt) (death: 481; transplant: 290; switch to HD: 511 pts). The main reason for transferring to HD remained peritonitis (28.2%). Peritonitis. The peritonitis rate (1,179 episodes) was 0.284 ep/yrs-pt. EPS. The incidence of new cases of EPS in 2011-12 (43 cases=0.505 ep/100yrs-pt) remained unchanged (2009-10= 0.529; 2004-08= 0.701 ep/100-yrs-pt). Other results. Compared to 2010, in 2012 the number of Centers using 3.86% for PET increased (30.8% vs 15.6%-p-0.001), while the number carrying out home visits remained unchanged (56.3 vs 59.4%). CONCLUSIONS: Cs-12 confirms the extensive use, stability and good results of PD in Italy. Incremental PD is on the increase. EPS remains a rare event.

Computer Aided Detection System for Prediction of the Malaise during Hemodialysis.

Monitoring of dialysis sessions is crucial as different stress factors can yield suffering or critical situations. Specialized personnel is usually required for the administration of this medical treatment; nevertheless, subjects whose clinical status can be considered stable require different monitoring strategies when compared with subjects with critical clinical conditions. In this case domiciliary treatment or monitoring can substantially improve the quality of life of patients undergoing dialysis. In this work, we present a Computer Aided Detection (CAD) system for the telemonitoring of patients' clinical parameters. The CAD was mainly designed to predict the insurgence of critical events; it consisted of two Random Forest (RF) classifiers: the first one (RF1) predicting the onset of any malaise one hour after the treatment start and the second one (RF2) again two hours later. The developed system shows an accurate classification performance in terms of both sensitivity and specificity. The specificity in the identification of nonsymptomatic sessions and the sensitivity in the identification of symptomatic sessions for RF2 are equal to 86.60% and 71.40%, respectively, thus suggesting the CAD as an effective tool to support expert nephrologists in telemonitoring the patients.

[Trend in PD in non-pediatric public centers in Italy: results of the 2010 GSDP-SIN census and comparison with the 2008 and 2005 censuses]. / Andamento della DP in Italia nei centri pubblici non pediatrici: Risultati del censimento GSDP-SIN 2010 e confronto con i censimenti 2008 e 2005.

The 2010 Italian Society of Nephrology Peritoneal Dialysis Study Group (GSPD-SIN) census (Cs-10) involved the 224 Centers performing PD in Italy. PD was used as 1st treatment in 23.3% (1429/4695) of pts (Cs-08:22.8%; Cs-05:24.2%), with 53.4% of them using CAPD. The use of incremental CAPD increased in Cs-10 (Cs-10:35.3%; Cs-08:25.7%; Cs-05:13.6%; p<0.0001). The number of prevalent pts was 4,222 (Cs-10:16.6%; Cs-08:16.6%; Cs-05:16.8%; p=NS), 45.7% of whom were on CAPD; 24.4% (Cs-08:21.8%; p<0.05) required assistance (family member:80.6%; caregiver:12.6%; nurse: 3.0%; RSA:3.4%). In Cs-10 the PD out rate (1,354 pts, of whom ep/100pt-yrs for drop-out: 12.4; death: 12.9; Tx: 7.5) was not different to previous years. The peritonitis rate was 0.30 ep/yr/pt, 18.5% of which with negative culture. There were 44 episodes of EPS in the period 2009-10 (0.53 ep/100yrs); while in the previous 5-year period there were 146 (0.70 ep/100pt-yrs). PET is performed by 98% of the centers, mostly using 2.27% (70.5%). Home visits are carried out by 59.1% of the centers. If regular (8.9% of the centers), they are associated with fewer ep/mth of peritonitis (61.2 vs 38.8) and lower drop-out (8.6 vs 12.8 ep/100 pt/yr - p<0.05) Cs-10 confirms the good results PD is having in the Centers that use it. Incremental CAPD and assisted PD are increasing. EPS remains a rare event. Standard PET is the most frequently-used evaluation of the peritoneal membrane. Though home visits are associated with lower peritonitis and drop-out rates, they are carried out regularly by a minority of the Centers.

Encapsulating peritoneal sclerosis.

The purpose of this best practice is to briefly define what has now been accepted regarding encapsulating peritoneal sclerosis (EPS), highlighting the latest developments and outlining future lines of research. The medical therapy that can be proposed (to be discussed individually, verifying the individual features of the patient) appears to include steroids, tamoxifen, and sirolimus or everolimus, with blood levels maintained at reference values for post-transplantation therapy. In view of the high incidence of relapse also in responders, it appears appropriate to continue therapy for prolonged periods, at least for 6 months. Moreover, a surgical assessment is indicated, especially for patients with intestinal symptoms including subocclusion status. To date the prevention of EPS is an unresolved issue. The recommended measures include the accurate prevention and best treatment of acute peritonitis, the use of biocompatible dialysis fluids (there is no consensus on their exact definition) and the monitoring of ultrafiltration characteristics and peritoneal membrane transport. Other recommended measures are the extensive use of renin-angiotensin- aldosterone axis inhibitors for the treatment of arterial hypertension in PD and the exclusion of beta- blockers. Other suggested strategies are tamoxifen prophylaxis in cases at risk and to adopt personalized immunosuppressive protocols for patients with PD who undergo renal transplantation.