Use Of Peritoneal Dialysis Fluid Research Articles

Pressure induces peritoneal fibrosis and inflammation through CD44 signaling

Peritoneal dialysis (PD) is a widely used sustainable kidney replacement therapy. Prolonged use of PD fluids is associated with mesothelial-mesenchymal transition, peritoneal fibrosis, and eventual ultrafiltration (UF) failure. However, the impact of pressure on the peritoneum remains unclear. In the present study, we hypothesized increased pressure is a potential contributing factor to peritoneal fibrosis and investigated the possible mechanisms. In vitro experiments found that pressurization led to a mesenchymal phenotype, the expression of fibrotic markers and inflammatory factors in human mesothelial MeT-5A cells. Pressure also increased cell proliferation and augmented cell migration potential in MeT-5A cells. The mouse PD model and human peritoneum equilibrium test (PET) data both showed a positive association between higher pressure and increased small solute transport, along with decreased net UF. Mechanistically, we found that significant upregulation of CD44 in mesothelial cells upon pressurization. Notably, the treatment of CD44 neutralizing antibodies prevented pressure-induced phenotypic changes in mesothelial cells, while a CD44 inhibitor oligo-fucoidan ameliorated pressure-induced peritoneal thickening, fibrosis, and inflammation in PD mice. To conclude, intraperitoneal pressure results in peritoneal fibrosis in PD via CD44-mediated mesothelial changes and inflammation. CD44 blockage can be utilized as a novel preventive approach for PD-related peritoneal fibrosis and UF failure.

Peritoneal Dialysis Solutions Low in Glucose Degradation Products—evidence for Clinical Benefits

In Japan, two types of new peritoneal dialysis fluid (PDF) are ordinarily used: two-chambered PDF, and icodextrin PDF. Two-chambered PDF has several biocompatible characteristics, one being low glucose degradation products (GDPs). Of the several GDPs in PDF, 3,4-dideoxyglucosone-3-ene (3,4-DGE) is thought to be strongly associated with the cytotoxicity of standard PDF. Using a PDF low in GDPs may reduce exposure of the peritoneum to 3,4-DGE, helping to preserve peritoneal function in PD patients. Additionally, use of a PDF low in GDPs may reduce plasma levels of advanced glycosylation end-products in PD patients, a change that may help to preserve vascular function in PD patients. Peritoneal rest for 24 hours after exposure to a PDF with low GDPs improves the activity of human peritoneal mesothelial cells. As compared with the use of standard PDF, the use of low-GDP PDF in combination therapy (peritoneal dialysis plus hemodialysis) may more effectively preserve peritoneal function. The new PDF low in GDPs has biocompatible characteristics relative to peritoneum and system that may help to preserve peritoneal function or reduce complications such as atherosclerosis or dialysis-related amyloidosis in dialysis patients.

MRI visualization of rodent liver structure and peritoneal adhesion with dialyzate enhancement

This study investigated the use of peritoneal dialysis fluid (dialyzate) as a MR contrast agent to visualize the liver structure and peritoneal adhesion in rats at 7 T. Intraperitoneal injection of dialyzate (approximately 0.1 ml/g) yielded excellent and consistent intraperitoneal enhancement that delineated the liver lobular structure in all rats studied (N = 8). It also allowed the MR detection of peritoneal adhesions that were surgically induced. MR measurements of adhesion surface areas correlated well with the postmortem estimations (R = 0.99; N = 6). Dialyzate persisted in the intraperitoneal cavity for up to 2 days. T(1) and T(2) values of undiluted dialyzate were found to be 3017.5 +/- 35.3 ms and 108.4 +/- 2.0 ms, respectively. These findings demonstrated dialyzate-enhanced MRI as a potentially valuable technique to localize certain activities within liver (such as local tumor metastasis), and to monitor therapeutic interventions (e.g., against peritoneal adhesion) in preclinical research using small animal models.

Damage to the Peritoneal Membrane by Glucose Degradation Products Is Mediated by the Receptor for Advanced Glycation End-Products

Peritoneal dialysis is limited by morphologic changes of the peritoneal membrane. Use of peritoneal dialysis fluids (PDF) that contain glucose degradation products (GDP) generates advanced glycation end-products (AGE) within the peritoneal cavity. It is unknown whether peritoneal damage is causally related to AGE-receptor for AGE (RAGE) interaction. The effects of PDF were compared with different amounts of GDP on morphologic changes of the peritoneal membrane in 48 wild-type (WT) and 48 RAGE-deficient mice. PDF (1 ml) were instilled twice daily over a period of 12 wk. Groups with eight animals each received no manipulation (sham); sham instillation (sham i.p.); or filter-sterilized, glucose-free, conventional low GDP- or high GDP PDF. In vitro (generation of AGE fluorescence in PDF) and in vivo (immunohistochemistry for carboxymethyllysine), a GDP-dependent increase of AGE formation occurred. Inflammation and neoangiogenesis were augmented in WT mice that were treated with high GDP accompanied by upregulation of CD3+ T cells, increased NF-kappaB binding activity, increased lectin, and vascular endothelial growth factor expression. Furthermore, pronounced submesothelial fibrosis was found with increased expression of TGF-beta1. Exposure to low GDP resulted in only mild inflammation and neoangiogenesis (compared with sham i.p.) and no fibrosis in WT mice. The findings in WT contrasted with those in RAGE-deficient mice, which showed no increased inflammation (CD3+ T cells and NF-kappaB binding activity), neoangiogenesis (by lectin and vascular endothelial growth factor expression), or fibrosis (expression of TGF-beta1) after long-term exposure to GDP-containing PDF. Peritoneal damage by GDP in PDF is dependent at least in part on AGE-RAGE interaction.

Peritoneal resuscitation

Background After resuscitation from hemorrhagic shock, intestinal microvessels constrict leading to impaired mucosal blood flow. This occurs despite restoration of central hemodynamics. We review studies on the use of peritoneal dialysis fluid as an adjunct treatment in amelioration of this gut hypoperfusion. Methods Using in vivo microscopy of the intestinal microcirculation, the effects of topically applied dextrose-based peritoneal dialysis fluid was measured. In other words, animal experiments, the survival benefits, the morbidity, blood flow distribution, and the postresuscitation inflammatory response to direct peritoneal resuscitation (DPR) were determined. Results Simulated DPR caused a dramatic vasodilation compared with a progressive vasoconstriction when used during conventional resuscitation (CR) from hemorrhagic shock. It also reversed established vasoconstriction 2 and 4 hours after CR. In CR animals, there was a 40% mortality compared with 100% survival in DPR animals. DPR resulted in a downregulation of the gut-associated proinflammatory response noted after CR and similarly prevented edema formation. Conclusion DPR enhances organ blood flow to organs incited in the pathogenesis of multiple organ failure and improves survival after severe hemorrhage and CR.