The mesothelium under the siege of dialysis solutions: old glucose, new glucose, and glucose-free osmotic agents.

Use of one bag of glucose peritoneal dialysis fluid (PDF) results in the development of a dose-related senescent mesothelial cell phenotype not linked to acidic pH or the presence of lactate buffer. This complication derives mostly from oxidative stress induced both by glucose itself and by glucose degradation products (GDPs). New glucose formulations are offered in dual- or three-chambered bags, keeping the glucose at a low pH.

Use of peritoneal dialysis and mesothelium in non primary renal conditions.

The management of a handful of non renal clinical conditions includes peritoneal dialysis (PD) as a therapeutic tool. Peritoneal lavage after abdominal surgery is still performed in infectious peritonitis and cases of necrotizing hemorrhagic pancreatitis. Use of PD in active psoriasis resulted in approximately 40 papers reporting mostly isolated cases and showing both therapeutic success and failure.

Preservation and modulation of peritoneal function. A potential role of pyruvate and betaine.

Aims: To review interventions aimed at protecting the peritoneal membrane from the detrimental effects of dialysis solutions, and to analyze proposed pharmacological interventions aiming to modulate peritoneal permeability. Main

Remarks: Sustained oxidative stress appears as the most relevant factor bringing about substantial damage to all the components of the peritoneal membrane. In vivo and in vitro studies suggest that pyruvate, a natural radical scavenger, may well neutralize or substantially reduce the oxidative insult.

Mechanisms of cell death during peritoneal dialysis. A role for osmotic and oxidative stress.

Aims: To offer a condensed description of the modes of cell death and the involved mechanisms behind them as detected in the different layers of the peritoneal tissue during experimental and clinical, long-term peritoneal dialysis (PD).

Main Remarks: Several types of cell death have been observed in the mesothelial monolayer: apoptosis, anoikis, secondary necrosis, pure necrosis and mitotic catastrophe. Death of mesothelial cells exposed to glucose-enriched solutions derives mainly from a degree of oxidative insult leading to DNA damage, provoked by glucose itself and/or its degradation products.

The use of peritoneal mesothelium as a potential source of adult stem cells.

At the dawn of the 21st century, classical curative medicine is being challenged by the fact that efforts to fight and prevent not a few diseases, are in many circumstances, beyond the power of the pharmacological armamentarium of the medical profession. On the other hand, replacement of lost function by mechanical or biophysical devices, or even by organ transplantation, prolongs life but generally derives in new and, at times, unsolvable problems. Regenerative therapy using stem cells began a revolutionary trend that may well change both the therapeutic approach to not a few of the diseases resulting from failing organs, as well as the fate and quality of life of millions of patients.

Agents that modulate peritoneal membrane structure and function.

Extensive experience with chronic peritoneal dialysis has identified a series of functional and anatomical pathologic changes in the peritoneal membrane thought to be the result of repeated insults from bioincompatible solutions. Laboratory and clinical findings from recent investigations often conflict and are difficult to interpret due to variations in methodologies, animal models, study designs, and data analyses. The principal pathophysiologic mechanisms identified thus far are oxidative stress, inflammation, and their consequences.

Peritoneal dialysis solutions--at a crossroad.

After many decades of evolution and with many choices available for the formulation of peritoneal dialysis fluids (PDF), we find ourselves at a crossroads. A review of related developments, laboratory trials and clinical evaluations is offered to stimulate future research in this area. The information presented here raises more questions than it provides answers, but opens the door to innumerable possibilities for improvement.

Iron deficiency is a common cause of anemia in chronic kidney disease and can often be corrected with intravenous iron.

Background: There is some epidemiological and clinical evidence that the anemia seen in chronic kidney disease (CKD) in patients not on dialysis could be due to a significant extent to iron deficiency, and that adequate iron replacement could cause a marked improvement in the anemia even without the use of erythropoietin (EPO). The purpose of this work was to study the effects of intravenous (i.v.

The impact of peritoneal dialysis upon quality of life and mortality of patients with end-stage congestive heart failure.

Background: Aged patients affected by congestive heart failure refractory to pharmacologic therapy, coupled with severe comorbidities that preclude heart transplantation have a gloomy prognosis. Use of automated peritoneal dialysis resulted in a significantly improved quality of life and survival.

Methods: Twenty patients (mean age: 65.

Repopulation of the mesothelial monolayer during long-term experimental peritoneal dialysis.

Background: Repopulation of the mesothelial monolayer after focal exfoliation, having the monolayer in vivo and in situ exposed to dialysis solutions, has not been thoroughly investigated. This study describes repopulation of a 'doughnut' like mesothelial ring exfoliated from the anterior liver surface of rats.

Methods: Animals were divided into 5 groups of 20 rats each.

Osmotic agents hamper mesothelial repopulation as seen in the doughnut in vivo model.

Background: The problem of mesothelial cell injury derived from the use of peritoneal dialysis solutions has been explored deeply. Conversely, the eventual detrimental effects upon mesothelial cell regeneration have awaked less investigative efforts than those focused on injury.

Objective: To evaluate in the in vivo and in situ rat "doughnut" model of mesothelial repopulation, the eventual effect of peritoneal lavage with Hank's Balanced Salt Solution (HBSS) as well as that of 4.

Peritoneal dialysis in refractory end-stage congestive heart failure: a challenge facing a no-win situation.

Background: Current medical therapeutic strategies for refractory congestive heart failure (CHF) in the population of 65 years and older with contraindications for heart transplantation are limited. Peritoneal dialysis applied to CHF patients with or without renal impairment showed clinical functional improvement.

Methods: A single centre, prospective but non-randomized study in 20 patients with severe congestive heart failure refractory to optimal pharmacological therapy [New York Heart Association (NYHA), class IV] was performed between 2000 and 2003.

A short review of experimental peritoneal sclerosis: from mice to men.

Peritoneal sclerosis has been induced in rodents in vivo by exposing the membrane to a variety of experimental interventions: asbestos, 0.1% chlorexidine, iron dextran, glucose degradation products, AGE deposits derived from uremia per se, sodium hypochlorite, lypopolysaccharide, low pH, pure water, silica or zymosan. With a few exceptions (pure water, chlorhexidine and low pH), the other substances mentioned operate setting out different degrees of oxidative stress.

Acute oxidative stress induces peritoneal hyperpermeability, mesothelial loss, and fibrosis.

We explored the acute and long-term effects of short-lived, intense oxidative stress on peritoneal permeability and structure, induced with intraperitoneal injection of the oxidant agent deoxycholate, in rats. Ten minutes after the experimental intervention, peritoneal dialysis, performed over an exposure time of 60 minutes, revealed an increased urea dialysate/plasma ratio, greater glucose absorption, increased albumin losses in the effluent dialysate, and a reduced ultrafiltration rate. Mesothelial-cell imprints taken from the anterior liver surface indicated a substantially decreased density in the cell population.

Icodextrin-induced lipid peroxidation disrupts the mesothelial cell cycle engine.

Fluids commonly used for peritoneal dialysis hold poor biocompatibility vis a vis the peritoneal membrane, basically due to the presence of osmotic agents. When rat mesothelium was exposed to glucose-enriched dialysis solutions for 2 h in vivo, an early and short-lived acceleration of cell life cycle was observed, which, after 30 d of exposure, resulted in a depopulated monolayer of senescent cells. These changes appear to result from persistent oxidative stress due to continuous exposure to high concentration of glucose and to substances generated by the Maillard reaction.

Peritoneal transport after long-term exposure to Icodextrin in rats.

Background: Icodextrin, an effective osmotic substance that has been proposed as an alternative agent for peritoneal dialysis induces ultrafiltration over long dwells. This study examines the peritoneal transport after exposure to Icodextrin in rats.

Methods: Animals were divided in 4 groups and injected daily for 30 days with Icodextrin 7.

Mesothelial dysplastic changes and lipid peroxidation induced by 7.5% icodextrin.

Background: The issue of icodextrin biocompatibility is somehow ambiguous. Whereas some experimental data point at better bicompatibility of icodextrin compared with high glucose concentration fluid, other reports showed substantial cytotoxic effects upon monocytes and cultured mesothelial cells. The present investigation exposes the first attempt to investigate the biocompatibility issue in an in vivo and in situ setup.

Continuous venovenous hemofiltration improves intensive care unit, but not hospital survival rate, in nonoliguric septic patients.

Purpose: The purpose of this study was to assess the effect of the early institution of continuous veno-venous hemofiltration on survival rates of nonoliguric, septic patients.

Materials And Methods: A retrospective study of 48 nonoliguric septic patients with PaO(2)/FIO(2) < or = 250, who were admitted to the General Intensive Care of the Soroka Medical Center. Twenty-six patients were treated with continuous venovenous hemofiltration (CVVH group) and 22 were treated by conventional therapy.

Protective effect of aminoguanidine upon capillary and submesothelial anionic sites.

This study evaluates albuminuria and peritoneal permeability to albumin in control and diabetic rats, as well as in diabetic animals treated with subcutaneously injected aminoguanidine hydrochloride (Ag) (5 mg/100 g/day), during a follow-up period of 6 months. Aminoguanidine effectively prevented albuminuria and albumin extravasation in the mesenteric interstitial tissue (control, 0.43 +/- 0.

High glucose accelerates the life cycle of the in vivo exposed mesothelium.

Background: Mouse mesothelium exposed in vivo for 30 days to high glucose solutions develop morphological changes that characterize a population of cells near the end of their life span.

Methods: The present study was designed to explore, in mesothelial cell imprints, whether these changes could derive from an early acceleration of the cell population life cycle in mice exposed for periods of up to 30 days to a 4.25% glucose fluid (236 mmol/L/L) prepared in Hank's balanced salt solution (HBSS).