The effects of high-flux dialysis and ultrapure dialysate on survival of hemodialysis patients are incompletely understood. We conducted a randomized controlled trial to investigate the effects of both membrane permeability and dialysate purity on cardiovascular outcomes. We randomly assigned 704 patients on three times per week hemodialysis to either high-or low-flux dialyzers and either ultrapure or standard dialysate using a two-by-two factorial design. The primary outcome was a composite of fatal and nonfatal cardiovascular events during a minimum 3 years follow-up. We did not detect statistically significant differences in the primary outcome between high-and low-flux (HR=0.73, 95% CI=0.49 to 1.08, P=0.12) and between ultrapure and standard dialysate (HR=0.90, 95% CI=0.61 to 1.32, P=0.60). Posthoc analyses suggested that cardiovascular event-free survival was significantly better in the high-flux group compared with the low-flux group for the subgroup with arteriovenous fistulas, which constituted 82% of the study population (adjusted HR=0.61, 95% CI=0.38 to 0.97, P=0.03). Furthermore, high-flux dialysis associated with a lower risk for cardiovascular events among diabetic subjects (adjusted HR=0.49, 95% CI=0.25 to 0.94, P=0.03), and ultrapure dialysate associated with a lower risk for cardiovascular events among subjects with more than 3 years of dialysis (adjusted HR=0.55, 95% CI=0.31 to 0.97, P=0.04). In conclusion, this trial did not detect a difference in cardiovascular event-free survival between flux and dialysate groups. Posthoc analyses suggest that high-flux hemodialysis may benefit patients with an arteriovenous fistula and patients with diabetes and that ultrapure dialysate may benefit patients with longer dialysis vintage.

BIS is a reliable method to evaluate volume status in PD patients. BIS performed after peritoneal equilibration test with an empty abdomen, better reflects overhydration and is related to echocardiographic parameters.

Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with ileus symptoms and irreversible sclerosis of the peritoneal membrane. Inflammation, fibrosis, and neoangiogenesis are the main features of the pathophysiology. No evidence-based therapy is currently available for EPS. In recent years, anti-inflammatory and immunosuppressive (IS) treatment modalities have become more popular. The aim of the present study was to investigate the effects of various IS treatment strategies—glucocorticosteroid (GC), azathiopurine (AZT), and cyclosporin (CsA)—on regression of EPS. We divided 52 nonuremic Wistar albino rats into six groups: Control group—2 mL isotonic saline injected intraperitoneally (IP) daily for 3 weeks; CG group—2 mL/200 g 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline injected IP daily for 3 weeks; Resting group—CG (weeks 1 – 3), plus peritoneal rest (weeks 4 – 6); Corticosteroid (GC) group—CG (weeks 1 – 3), plus 10 mg/L prednisolone in drinking water (weeks 4 – 6); AZT group—CG (weeks 1 – 3), plus 100 mg/L azathioprine in drinking water (weeks 4 – 6); and CsA group—CG (weeks 1 – 3), plus cyclosporin 7.5 mg/kg by subcutaneous injection daily (weeks 4 – 6). At the end of the study, under ketamine HCl anesthesia, the rats were humanely killed by bleeding. Parietal peritoneal samples were then taken from same location (away from the injection site) and changes of parietal peritoneum morphology were examined by a single pathologist. The CG severely disturbed parameters of peritoneal morphology, increasing peritoneal thickness, inflammatory activity, vascularity, and fibrosis score as compared with the Control group ( p < 0.05). No benefit was observed for any parameter in the Resting group as compared withthose parameters in the CG group ( p < 0.05). We observed a lower fibrosis score and less peritoneal thickness in the GC group as compared with the Resting group ( p < 0.05). No beneficial effects of AZT on peritoneal morphology were observed as compared with the effects of peritoneal rest or corticosteroid therapy. Treatment with cyclosporin resulted in more fibrosis, vascularity, and inflammation than was seen with corticosteroid therapy ( p < 0.05). Immunosuppressive therapies, especially those that are corticosteroid-based, may have therapeutic value in the management of EPS. Patients treated with cyclosporin may have a risk for developing EPS.

Background Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with symptoms of ileus and irreversible sclerosis of both visceral and parietal peritoneum. Peritoneal dialysis (PD) patients rarely develop EPS, a severe life-threatening condition of unknown pathogenesis. Angiotensin II is known to promote fibrosis and inflammation in various tissues. Renin–angiotensin system (RAS) blockade provides advantages in the course of diseases such as hypertension, chronic kidney disease, and proteinuria. We have also previously shown that RAS blockade has beneficial effects on hypertonic (3.86%) PD solution-induced peritoneal alterations. Because it shares the same characteristics as other fibrotic processes, peritoneal fibrosis can benefit from RAS blockade. Objective To determine the advantages of RAS blockade in regression of EPS. Methods We divided 56 nonuremic albino Wistar rats into 6 groups: control group ( n = 10), daily intraperitoneal (IP) injection of 2 mL isotonic saline for 3 weeks; CG group ( n = 10), daily IP injection of 2 mL/200 g chlorhexidine gluconate (CG) for 3 weeks; resting group ( n = 10), daily IP injection of CG (0 – 3 weeks) plus peritoneal rest (4 – 6 weeks). After 3 weeks of being injected with CG (0 – 3 weeks), a fourth group ( n = 9) was treated with 100 mg/L enalapril (ENA group); a fifth group ( n = 10) was treated with 80 mg/L valsartan (VAL group), and a sixth group ( n = 7) was treated with 100 mg/L enalapril + 80 mg/L valsartan (ENA+VAL group) in drinking water for an additional 3 weeks (4 – 6 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume (UF), and morphological changes of parietal peritoneum were examined. Results Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Peritoneal rest had some beneficial effect only on UF failure and dialysate cell count ( p < 0.05). However, RAS blockade was more effective than peritoneal rest with respect to UF volume, vascularity ( p < 0.05), and peritoneal thickness ( p > 0.05). Dual blockade of RAS had no additional beneficial effects. Conclusion We suggest that RAS blockade either with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be a more effective option than resting in the management of EPS.

Long-term use of the peritoneum as a dialysis membrane results in progressive irreversible dysfunction, described as peritoneal fibrosis. Oxidative stress during peritoneal dialysis has been established in many studies. Generation of reactive oxygen species (ROS) by conventional peritoneal dialysis solutions, regardless of whether produced by high glucose, angiotensin II, or glucose degradation products may be responsible for progressive membrane dysfunction. The well-known antioxidant molecule N-acetylcysteine (NAC) is capable of direct scavenging of ROS. The aim of the present study was to investigate the effect of NAC therapy on both progression and regression of encapsulating peritoneal sclerosis (EPS). We divided 49 nonuremic Wistar albino rats into four groups: Control group—2 mL isotonic saline intraperitoneally (IP) daily for 3 weeks; CG group—2 mL/200 g 0.1% chlorhexidine gluconate (CG) and 15% ethanol dissolved in saline injected IP daily for a total of 3 weeks; Resting group—CG (weeks 1 – 3), plus peritoneal resting (weeks 4 – 6); NAC-R group—CG (weeks 1 – 3), plus 2 g/L NAC (weeks 4 – 6). At the end of the experiment, all rats underwent a 1-hour peritoneal equilibration test with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio (D/P) urea, dialysate white blood cell count (per cubic milliliter), ultrafiltration (UF) volume, and morphology changes of parietal peritoneum were examined. The CG group progressed to encapsulating peritoneal sclerosis, characterized by loss of UF, increased peritoneal thickness, inflammation, and ultimately, development of fibrosis. Resting produced advantages only in dialysate cell count; with regard to vascularity and dialysate cell count, NAC was more effective than was peritoneal rest. Interestingly, we observed no beneficial effects of NAC on fibrosis. That finding may be a result of our experimental severe peritoneal injury model. However, decreased inflammation and vascularity with NAC therapy were promising results in regard to membrane protection.