Effects Of Peritoneal Dialysis Solutions Research Articles

P0176REGULATION OF OXALATE HOMEOSTASIS BY OXALATE-DEGRADING ACTIVITY IN FECAL MICROBIOTA IN DIALYSIS PATIENTS

Abstract Background and Aims Despite evidence suggesting that a lack of fecal oxalate-degrading bacteria colonization is a risk factor for calcium oxalate stone formation, little is known about the oxalate-degrading activity (ODA) in fecal microbiota in end-stage renal disease (ESRD) patients. In addition, to date, there has been a general lack of research on the effect of fecal ODA on oxalate homeostasis in dialysis patients. The present pilot cross-sectional study was performed to compare the oxalate homeostasis profiles depending on ODA in fecal microbiota in ESRD patients. Method The data of a cross-sectional pilot study examining ODA in fecal microbiota, plasma oxalate concentration (POx) and urinary oxalate excretion (UOx) in 32 ESRD patients were represented in this study. Among the patients, there were 21 hemodialysis (HD) patients and 11 peritoneal dialysis (PD) patients. The average age of the patients was 52.5 [39; 65] years. The redoximetric titration with KMnO4 was adopted to evaluate total ODA in fecal microbiota. The results were expressed in % oxalate degradation per 0.01 g of feces. POx concentration and UOx excretion were measured spectrophotometrically using a commercially available kit (MAK-315, Sigma, Spain) and an oxalate oxidase/peroxidase reagent (BioSystems, Spain), respectively. Predialysis plasma samples were collected from HD patients. For further analysis, the patients were allocated to 2 groups according to ODA in feces. Group 1 included the patients with ≥ 1 % oxalate degradation per 0.01 g of feces. Group 2 included the patients with negative ODA (≤ 0 % /0.01 g). For the statistical analysis, we used the nonparametric Kruskal-Wallis test. The median (Me) and interquartile ranges [Q25; Q75] were calculated. The Spearman test was used for the correlation analysis. Univariate logistic regression analysis was used for predicting hyperoxalemia. All statistical analyses were performed using MedCalc. Results ODA in fecal microbiota ranged from -23 to 24 %/0.01 g of feces in ESRD patients and was statistically higher in HD patients compared with PD patients (3.2 [-0.5; 16] vs -4 [-6.5; 6.2], p=0.05). Negative ODA in fecal microbiota (≤ 0 % /0.01 g) was observed in 5/21 (23.8%) HD patients and 7/11 (63.6%) PD patients (χ2=3.9, p=0.04). Consequently, it might be associated with the negative effects of peritoneal dialysis solution. High POx concentration and low UOx excretion were diagnosed in patients with negative ODA in fecal microbiota (Group 2): 30.7 [25.5; 41.5] vs 50 [43.3; 75.5] μmol/L, p=0.01 and 60.9 [51; 65] vs 34.2 [24.4; 39] mg/d, p=0.0002, respectively (Fig. 1). Fecal ODA was directly associated with daily UOx excretion (r=0.85; p<0.0001) (Fig. 2) and had an inverse correlation with POx concentration (r=-0.36; p=0.04) (Fig. 3). In univariate logistic regression analysis, negative fecal ODA was determined as an independent risk factor for high POx concentration (OR: 40; 95% CI: 4.8-331, p<0.0001). Conclusion Our pilot cross-sectional study firstly demonstrated a close association between ODA in fecal microbiota and oxalate homeostasis in ESRD patients: less ODA in fecal microbiota was, higher POx concentration and lower UOx excretion occurred. We suppose that the potential significance of our findings provides preliminary information on the feasibility and necessity of further research in this area.

Unfavorable Effects of Peritoneal Dialysis Solutions on the Peritoneal Membrane: The Role of Oxidative Stress.

One of the main limitations to successful long-term use of peritoneal dialysis (PD) as a renal replacement therapy is the harmful effects of PD solutions to the structure and function of the peritoneal membrane (PM). In PD, the PM serves as a semipermeable membrane that, due to exposure to PD solutions, undergoes structural alterations, including peritoneal fibrosis, vasculopathy, and neoangiogenesis. In recent decades, oxidative stress (OS) has emerged as a novel risk factor for mortality and cardiovascular disease in PD patients. Moreover, it has become evident that OS plays a pivotal role in the pathogenesis and development of the chronic, progressive injury of the PM. In this review, we aimed to present several aspects of OS in PD patients, including the pathophysiologic effects on the PM, clinical implications, and possible therapeutic antioxidant strategies that might protect the integrity of PM during PD therapy.

Effect of peritoneal dialysis solution with different pyruvate concentrations on intestinal injury.

To investigate the effects of direct peritoneal resuscitation with pyruvate-peritoneal dialysis solution (Pyr-PDS) of different concentrations combined with intravenous resuscitation on acid–base imbalance and intestinal ischemia reperfusion injury in rats with hemorrhagic shock. Sixty rats were randomly assigned to group SHAM, group intravenous resuscitation, and four direct peritoneal resuscitation groups combined with intravenous resuscitation: group NS, LA, PY1, and PY2, that is, normal saline, lactate-PDS (Lac-PDS), lower concentration Pyr-PDS (Pyr-PDS1), and higher concentration Pyr-PDS (Pyr-PDS2), respectively. Two hours after hemorrhagic shock and resuscitation, the pH, oxygen partial pressure, carbon dioxide partial pressure (PCO2), base excess, and bicarbonate ion concentration (HCO3−) of the arterial blood were measured. The intestinal mucosal damage index and intercellular adhesion molecule 1 (ICAM-1), tumor necrosis factor-α, interleukin-6, zonula occludens-1, claudin-1, and occludin levels in intestinal issues were detected. Two hours after resuscitation, group PY2 had higher mean arterial pressure, pH, oxygen partial pressure, and base excess and lower PCO2of arterial blood than group PY1 ( P < 0.05). Tumor necrosis factor-α and interleukin-6 levels in group PY2 were significantly lower than those in group PY1 ( P < 0.05). Zonula occludens-1, claudin-1, and occludin expression levels were significantly higher in group PY2 than in group PY1 ( P < 0.05). Direct peritoneal resuscitation with Pyr-PDS2 combined with intravenous resuscitation enhanced the hemodynamics, improved the acid–base balance, and alleviated intestinal ischemia reperfusion injury from hemorrhagic shock and resuscitation in rats. The mechanisms might include correction of acidosis, inhibition of inflammatory response, enhancement of systemic immune status, regulation of intestinal epithelial permeability, and maintenance of intestinal mucosal barrier function.Impact statementHemorrhagic shock is a life-threatening condition after trauma or during surgery. Acid–base imbalance and intestinal ischemia reperfusion injury are two significant causes in the pathogenetic process and multiple organ dysfunction. As a result, it is urgent and necessary to find an effective method of resuscitation in order to reverse the acid–base imbalance and protect organ function. This current study confirmed the protection against hypoxic acidosis and intestinal ischemia reperfusion injury by peritoneal resuscitation with pyruvate combined with intravenous resuscitation in rats with hemorrhagic shock. And the peritoneal dialysis solution with pyruvate of high concentration plays a crucial role in the process. It provided a new idea and possible direction of fluid resuscitation for alleviating organ injuries, protecting organ functions, and improving clinical prognosis after hemorrhagic shock and resuscitation.

Risk factors of acute renal impairment after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Background Acute renal impairment (ARI) is a major complication after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for cancer patients with peritoneal metastases. This study aimed to investigate the incidence and identify the risk factors of post-HIPEC creatinine increased. Methods From April 2015 to December 2019, demographic and perioperative data of 169 patients undergoing CRS/HIPEC with a preoperative creatinine level <1.5 mg/dL were retrospectively reviewed. Renal impairment was defined according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. The risk factors of creatinine increased were analyzed using univariate and multiple logistic regression analyses. Results Among the 169 enrolled patients, 21 (12.4%) had postoperative creatinine increased (ARI group) and 148 (87.6%) did not (non-ARI group). Significantly more of the ARI group received a cisplatin HIPEC regimen than the non-ARI group (71.4 vs. 37.8%, p = 0.004). Multiple logistic regression analysis revealed that the patients who received a cisplatin HIPEC regimen (adjusted odds ratio [AOR] = 11.38, p < 0.001) and peritoneal dialysis solution as HIPEC perfusate (AOR = 7.07, p = 0.002) were more likely to develop post-HIPEC creatinine increased. Conclusions Identifying the risk factors of post-HIPEC creatinine increased can help to improve patient selection, a dose of HIPEC regimens modification and perioperative care. We also identified the detrimental renal effect of peritoneal dialysis solution as HIPEC perfusate. More prospective studies are warranted to confirm these findings.

Recent advances in the management of peritoneal dialysis patients.

Peritoneal dialysis is a form of kidney dialysis that is used to remove accumulated metabolic waste products and water in patients with end stage kidney disease. Long-term exposure to high concentrations of glucose and its by-products, both found in peritoneal dialysis fluid, has been implicated in contributing to peritoneal damage over time, in turn limiting long-term use of the technique. Newer peritoneal dialysis solutions have been developed in the hope of reducing the unfavorable effects of peritoneal dialysis solutions. In vitro and in vivo studies have suggested that newer peritoneal dialysis fluids have salutary effects on the peritoneal membrane. Short-term clinical studies have also found some metabolic benefits of glucose-sparing regimens in chronic peritoneal dialysis. Mixed results have been found in studies examining whether newer peritoneal dialysis fluids reduce peritonitis rates. Long-term studies are needed to investigate whether newer peritoneal dialysis fluids provide better peritoneal dialysis technique and/or patient survival, compared to standard glucose-based peritoneal dialysis fluids.

Increasing the use of biocompatible, glucose-free peritoneal dialysis solutions.

A major concern inhibiting some clinicians from embracing peritoneal dialysis (PD) as the preferred first modality of dialysis is the effects of PD solutions on the peritoneal membrane. These anatomical and functional changes predispose to complications like peritonitis, encapsulating peritoneal sclerosis and ultrafiltration failure. In recent years, "biocompatible" and glucose-sparing PD regimens have been developed to minimize damage to the peritoneal membrane. Can the use of these more expensive solutions be justified on current evidence? In this review of the literature, we explore how we may individualize the prescription of biocompatible PD fluid.

Comparative in vitro Study of Different Peritoneal Dialysis Solutions on Cytokine Production by Peripheral Blood Mononuclear Cells

Background/Aims: Peritoneal dialysis solutions (PDS), new and conventional, do not yet have a clinical biocompatibility profile. We aimed at a comparative laboratory profile based on the effect of PDS on peripheral blood mononuclear cell (PBMC) cytokine release. Method: PBMCs from 19 healthy volunteers were incubated at a concentration of 10⁶/ml in fresh PDS and control medium (RPMI 1640), and stimulated or not with 10μg/ml Escherichia coli lipopolysaccharide. The tested PDS were glucose/lactate 1.5 and 4.25%, glucose/pyruvate 1.0 and 4.0%, icodextrin and amino acid solutions. The initial incubation in culture flasks for 15 min was followed by 1:1 dilution with RPMI and by additional incubation for 22 h as a ‘recovery period’. At the end, the supernatants were tested for cytokines IL-6 and TNFα by ELISA. Results: The hypertonic glucose solutions, irrespective of the buffer, had the most adverse effect on PBMC cytokine release. The icodextrin and amino acid solutions seemed close to the isotonic glucose PDS. The substitution of pyruvate for lactate buffer seemed to offer an advantage only for the hypertonic glucose-based solutions. Conclusions: Icodextrin and amino acid solutions seem to offer an advantage only compared to hypertonic glucose PDS.

Acute effects of peritoneal dialysis solutions in the mesenteric microcirculation

Long-term peritoneal dialysis induces morphological changes that may lead to gradual functional impairment of the peritoneal membrane. These changes are characterized by progressive reduction in solute transport or ultrafiltration failure. The mechanism of the peritoneal response to dialysis fluids has not yet been fully elucidated. We used video-microscopy for in vivo evaluation of microhemodynamics and peritoneal microvascular inflammatory response, after a single intraperitoneal exposure of rats to commercial PD fluids: (1) glucose 1.5 % PD solution; (2) lactate buffered glucose 4.25% PD solution; (3) Icodextrin 7%; (4) bicarbonate buffered glucose 3.86% PD fluid; and 5) Hanks solution. Sham-control groups were not injected. A 5-h exposure of the peritoneal membrane to glucose 1.5% PD solution or to Hanks solution did not induce a significant change in leukocyte rolling and adhesion. In contrast, PD solutions containing glucose 4.25% or Icodextrin 7.5% caused a significant 2-3-fold increase in leukocyte rolling (P < 0.001) and adhesion (P < 0.001) and a significant increase in venular blood flow velocity (P < 0.01) and shear rates (P < 0.05 for glucose 4.25%, and P < 0.01 for Icodextrin). Exposure to glucose 3.86% bicarbonate buffered (Physioneal) solution was associated with the lowest values of leukocyte rolling and adhesion among the PD solutions and with extremely higher venular flow velocities and shear rates. A single exposure to conventional PD solutions with a high concentration of glucose (4.25%) or polyglucose (Icodextrin 7.5%) induces changes consistent with an early peritoneal inflammatory response that may be attenuated by the use of bicarbonate-based fluids.

Clinical Outcome Following the Use of Inadequate Solutions for Continuous Veno-Venous Hemodiofiltration

Backgrounds. A short time ago, commercially available diafiltration and replacement fluids could be found o n the hospital in Turkey. Instead, peritoneal dialysis solution (PDS) for continue veno-venous hemodiafiltration (CVVHDF) therapy and normal saline as replacement fluid are used. In this retrospective study, we investigated the effects of PDS and bicarbonate-buffered hemofiltration solution (Bic-HFS). Methods. We did a retrospective chart review of 24 patients treated with continue renal replacement therapy (CRRT) between January 2004 and February 2008. Peritoneal dialysis solution (PDS) was used in 14 patients, and bicarbonate-buffered hemodialysis solution (bic-HFS) was used in 10 patients. Results. Demographic data, laboratory findings, and mortality rate were similar both groups. Blood glucose and lactate levels were higher in the PD group than the bic-HFS group (p < 0.05). Hyperglycemia occurred more frequent in the PDS group than in the bic-HFS group (64% versus 30%, respectively; p < 0.05). Metabolic acidosis occurred in eight patients (57%) in the PDS group and three patients (30%) in the bic-HFS group (p < 0.05). Hypotension was higher in the PDS group (10, 71%) than in the bic-HFS group (3, 30%; p < 0.05). Conclusion. Using PDS fluid as dialysate for CVVHDF therapy is not a preferable solution because of the metabolic disturbances that it can cause.

Effect of Peritoneal Dialysis Solution Type on Serum Lipid Levels in End-Stage Renal Disease

Among the different cardiovascular risk factors, lipid abnormalities dominate the high mortality in chronic ambulatory peritoneal dialysis patients. So far, no data comparing the effect of standard glucose-containing, amino acid-containing, and icodextrin-containing peritoneal dialysis solutions on serum lipid concentrations in a chronic ambulatory peritoneal dialysis population are available. To determine the effect of peritoneal dialysis solutions on parameters of lipid metabolism, 67 subjects who had continued their usual dialysis for the last six months were enrolled in the study. Group A consisted of 18 patients who were receiving only glucose-based peritoneal dialysis solutions, group B consisted of 18 patients who were receiving glucose and amino acid-based peritoneal dialysis solutions, and group C consisted of 31 patients who were receiving glucose and icodextrin-based peritoneal dialysis solutions. Serum lipid parameters including total cholesterol, low-density lipoprotein, high-density lipoprotein, triglyceride, and lipoprotein (a) were determined in all groups. No significant difference in serum lipid parameters was found between groups A, B, and C. These results demonstrate the lack of the effect of amino acid or icodextrin-based peritoneal solutions on dyslipidemia of CAPD patients.

Effects of Peritoneal Dialysis Solutions on the Secretion of Growth Factors and Extracellular Matrix Proteins by Human Peritoneal Mesothelial Cells

To compare the effects of different peritoneal dialysis solutions (PDS) on secretion of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGFbeta1), procollagen I C-terminal peptide (PICP), procollagen III N-terminal peptide (PIIINP), and fibronectin by cultured human peritoneal mesothelial cells (HPMC). Using M199 culture medium as control, commercial PDS containing 1.5% or 4.25% glucose and 40 mmol/L lactate [Dianeal 1.5 (D 1.5) and Dianeal 4.25 (D 4.25), respectively; Baxter Healthcare, Deerfield, Illinois, USA]; PDS containing 1.5% or 4.25% glucose with 25 mmol/L bicarbonate and 15 mmol/L lactate [Physioneal 1.5 (P 1.5) and Physioneal 4.25 (P 4.25), respectively; Baxter]; and PDS containing 7.5% icodextrin [Extraneal (E); Baxter] were tested. Growth-arrested and synchronized HPMC were continuously stimulated for 48 hours by test PDS diluted twofold with M199, TGFbeta1 1 ng/mL, or different concentrations of icodextrin. VEGF, TGFbeta1, and fibronectin secreted into the media were analyzed by ELISA, and PICP and PIIINP by radioimmunoassay. Dianeal 1.5, D 4.25, and P 4.25, but not P 1.5 and E, significantly increased VEGF secretion compared with control M199. D 4.25- and P 4.25-induced VEGF secretion was significantly higher than induction by D 1.5 and P 1.5, respectively, suggesting that high glucose may be involved in the induction of VEGF. Physioneal 1.5- and P 4.25-induced VEGF secretion was significantly lower than induction by D 1.5 and D 4.25, respectively, suggesting a role for glucose degradation products (GDP) in VEGF production. TGFbeta1 secretion was significantly increased by D 4.25 and E. Icodextrin increased TGFbeta1 secretion in a dose-dependent manner. All PDS tested significantly increased secretion of PIIINP compared with control. D 1.5- and D 4.25-induced PIIINP secretion was significantly higher than P 1.5, P 4.25, and E. Physioneal 4.25-induced PIIINP secretion was significantly higher than P 1.5, again implicating high glucose and GDP in PIIINP secretion by HPMC. There was no significant increase in PICP or fibronectin secretion using any of the PDS tested. Addition of TGFbeta1 1 ng/mL into M199 control significantly increased VEGF, PICP, PIIINP, and fibronectin secretion by HPMC. The present study provides direct evidence that HPMC can secrete VEGF, TGFbeta1, and PIIINP in response to PDS, and that HPMC may be actively involved in the development and progression of the peritoneal membrane hyperpermeability and fibrosis observed in long-term PD patients. This study also suggests that both high glucose and GDP in PDS may play important roles in inducing VEGF and PIIINP production/secretion by HPMC.

Hemodynamic effects of peritoneal dialysis solutions on the rat peritoneal membrane: role of acidity, buffer choice, glucose concentration, and glucose degradation products.

Conventional peritoneal dialysis fluids (PDF) are unphysiologic because of their hypertonicity, high glucose and lactate concentrations, acidic pH, and presence of glucose degradation products (GDP). Long-term exposure to conventional PDF may cause functional and structural alterations of the peritoneal membrane. New PDF have a neutral pH, a low GDP content, and contain bicarbonate or lactate as the buffer. Intravital microscopy was used to analyze the vasoactive effects of conventional and new PDF on the rat peritoneal membrane. A conventional, acidic pH, lactate-buffered 4.25% glucose PDF induced maximal vasodilation of mesenteric arteries, resulting in a doubling of the arteriolar flow and a 20% increase of the perfused capillary length per area. The hemodynamic effects of conventional PDF were similar after pH-adjustment with NaOH, indicating that acidity per se is not essential for the changes. Superfusion by a pH-neutral, lactate-buffered PDF with low GDP content caused only a transient arterial vasodilation despite continuous exposure, with a commensurate effect on arteriolar flow and capillary recruitment. Application of a pH-neutral, bicarbonate-buffered PDF with low GDP content did not affect the hemodynamic parameters. Resterilization of the bicarbonate solution increased GDP levels and completely restored the vasodilatory capacity. The corresponding 1.5% glucose PDF induced similar but less pronounced changes. Conventional PDF have important vasoactive effects on the peritoneal circulation, mainly because of the presence of GDP and transiently because of high lactate concentrations. Capillary recruitment may increase effective peritoneal vascular surface area. In addition, chronic vasodilation may induce structural adaptations in the blood vessel wall, contributing to vascular sclerosis. PDF with reduced GDP content induce no major hemodynamic effects and may thus have the potential to better preserve peritoneal vascular integrity.

Acute effects of peritoneal dialysis solutions on appetite in non-uremic rats

Standard peritoneal dialysis (PD) solutions may contribute to anorexia in PD patients due to the peritoneal absorption of glucose from the dialysate, abdominal discomfort and other factors. New PD solutions containing alternative osmotic agents, neutral pH and bicarbonate as buffer were recently developed. To test the effect of these solutions on appetite, we investigated how intraoral (IO) intake of sucrose via an IO cannula was influenced by intraperitoneal (IP) infusion of different PD solutions in an appetite model in rats. The IO intake was measured in male Wistar rats after an IP dwell of 30 and 120 minutes with the following PD solutions: 1.36%, 2.27% and 3.86% glucose based and lactate buffered solutions (D); 1.36%, 2.27% and 3.86% glucose based and bicarbonate/lactate buffered solutions (P); 7.5% icodextrin based solution (E); 1.1% amino acid-based solution (N); and, 2.5% glucose-based lactate-buffered solution (GB), using sham injection (injection without infusion) as control. Prior to the tests, rats were provided with an IO cannula, and were trained for two weeks until the rate of IO intake had stabilized. The D and N solutions inhibited IO intake. For the D solutions, the degree of appetite suppression was higher with the higher concentration of glucose. P 3.86%, but not P 1.36% and P 2.27% solutions, inhibited the IO intake. However, a comparison of the degree of appetite inhibition between D and P showed less inhibition with P 1.36%, 2.27% and 3.86% solutions than with corresponding D solutions. The E solution did not seem to suppress appetite. Finally, no significant difference in IO intake was found between rats given GB 2.5% and D 2.27%. In this appetite model in rats, the measurement of IO intake after the IP infusion of different dialysis solutions showed that (1) N and D solutions may reduce appetite, and for the D solutions the degree of appetite inhibition was related to the dialysate concentrations of glucose; (2) the P solutions had less impact on appetite than the D solutions; (3) the E solution had no impact on appetite during the short dwells of 30 and 120 minutes. The demonstrated differences between the different solutions appear to be due to different concentrations, and type, of nutrients used as osmotic agent (glucose, amino acids, icodextrin) or buffer (lactate), although differences in dialysate pH, tonicity and concentration of glucose degradation products also may be important. The present studies suggest a possible positive effect on appetite by using bicarbonate/lactate buffered solutions instead of lactate buffered solutions.

Acceleration of neutrophil apoptosis by glucose-containing peritoneal dialysis solutions: role of caspases.

Commercial, glucose-containing peritoneal dialysis (PD) solutions have deleterious effects on leukocytes and mesothelial cells that contribute to an impaired peritoneal defense. However, the molecular mechanisms of these deleterious effects are poorly understood. The effect of PD solutions on neutrophil viability, the molecular mechanisms of cell death, its functional consequences, and the possibilities for pharmacologic modulation have now been studied. The effect of newly available, bicarbonate-buffered PD solutions were further investigated. Lactate-buffered, glucose-containing PD solutions increased the apoptosis rate of cultured neutrophils (control media versus 4.25% glucose PD solution: 31 +/- 3% versus 52 +/- 3% apoptosis at 24 h, P < 0.001). Bicarbonate-buffered, 4.25% glucose-containing PD solutions with low concentration of glucose degradation products did not increase the rate of apoptosis. Apoptosis induced by lactate-buffered, 4.25% glucose PD solutions was not related to hyperosmolality or acidic pH and was not reproduced by increasing the glucose concentration by the addition of glucose to a commercial, lactate-buffered fluid. Neutrophil apoptosis was associated with caspase-3 activation. Inhibition of caspase-3 by the use of the caspase-3 inhibitor acetyl-Asp-Glu-Val-Asp-fmk or the broad-spectrum caspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp-fluoromethylketone (zVAD-fmk) prevented features of apoptosis, such as morphologic changes, internucleosomal DNA degradation, and the appearance of hypodiploid cells and increased the number of viable, trypan blue-excluding neutrophils. Furthermore, zVAD-fmk increased neutrophil phagocytosis of bacteria. However, the caspase-1 inhibitor acetyl-Tyr-Val-Ala-Asp-aldehyde did not prevent cell death. These data suggest that unidentified components in commercial, lactate-buffered, high-glucose PD fluid accelerate the rate of neutrophil apoptosis. Glucose degradation products may be such unidentified components. Acceleration of neutrophil apoptosis may contribute to the impaired local defense system of patients undergoing PD.

L-2-oxothiazolidine-4-carboxylic acid modulates function of peritoneal mesothelial cells in vitro.

The influence of the glutathione precursor, l-2-oxothiazolidine-4-carboxylic acid (OTZ), on the function of human peritoneal mesothelial cells in vitro, in conditions that mimic the in vivo effect of peritoneal dialysis solutions on mesothelium, was studied. Mesothelial monolayers were exposed to dialysis fluids (Dianeal 1.36 or Dianeal 3.86; Baxter Healthcare Corp, Round Lake, IL) that were diluted gradually with pooled-effluent dialysate obtained from patients undergoing continuous ambulatory peritoneal dialysis. In vitro exposure of mesothelium to standard dialysis fluid enhances their susceptibility to injury by hydrogen peroxide. OTZ added to dialysis solution in concentrations of 1 mmol/L prevented the toxic effect of hydrogen peroxide, probably by increasing intracellular glutathione. Mesothelial cells exposed to dialysis fluid become activated, evidenced by increased release of interleukin-6 and hyaluronan. OTZ used in concentrations of 1 mmol/L reduced that effect. Furthermore, the addition of glucose to the culture medium in a concentration of 45 mmol/L inhibits the proliferation of mesothelial cells; the presence of OTZ, 1 mmol/L, partially prevents the inhibitory effect of glucose. The results presented in this report show that by augmenting the intracellular concentration of glutathione in mesothelial cells by the addition of OTZ to the dialysis fluid, we can increase their resistance to the acute toxicity of free radicals and long-term toxicity of glucose. In addition, mesothelial cells with an increased glutathione level are less activated after their exposure to dialysis fluid.

In Vivo Model to Study the Biocompatibility of Peritoneal Dialysis Solutions

This study was designed to analyze the complex morphologic and functional effects of dialysis solutions on peritoneum in a rat model on chronic peritoneal dialysis. Peritoneal catheters were inserted into 10 male, Wistar rats and the animals were dialyzed twice daily for 4 weeks with 4.25% Dianeal. During the study we observed two opposite effects: healing of the peritoneum after catheter implantation--decreased cell count in dialysate, decreased permeability of the peritoneum to glucose and total protein, increased volume of drained dialysate; and damage to the membrane due to its exposure to peritoneal dialysis solution--increased hyaluronic acid levels in dialysate, a tendency of the peritoneum to thicken when compared to non-dialyzed animals. Our rat model of CAPD may be used for quantitative and qualitative assessment of the effects of peritoneal dialysis solution on the peritoneum during chronic dialysis.

In vitro simulation of the effect of peritoneal dialysis solution on mesothelial cells

All previous in vitro biocompatibility tests of peritoneal dialysis fluids have shown that these have inhibitory effects on the function of peritoneal mesothelium. This report presents results from in vitro experiments performed to study the effect of dialysis fluids (Dianeal 1.36 and Dianeal 3.86; Baxter, Round Lake, IL) on the function of mesothelial cells under conditions that simulate the in vivo state of these solutions in the peritoneal cavity. Thus, cells were initially exposed only to the unused fluids that were thereafter gradually diluted (over 4 hours) with pooled effluent dialysate from continuous ambulatory peritoneal dialysis patients. During the following 20 hours, cells were incubated in a mixture of unused fluid (10% vol/vol) and dialysate effluent (90% vol/vol). The mesothelial cells exposed to dialysis fluids under such conditions became activated cells compared with exposed to dialysate effluent (control) alone. Thus, synthesis by mesothelial cells of all tested substances was enhanced during exposure of the mesothelium to the dialysis fluids: interleukin-6: Dianeal 1.36, +257%; Dianeal 3.86, +181% (both P < 0.05); hyaluronic acid: Dianeal 1.36, +72%; Dianeal 3.86, +63% (both P < 0.05); tissue plasminogen activator: Dianeal 3.86, +33% ( P < 0.05); and plasminogen activator/inhibitor-1: Dianeal 1.36, +28%; Dianeal 3.86, +38% (both P < 0.05). Our results show that the peritoneal mesothelium becomes activated when it is exposed to acidic, hyperosmotic dialysis fluids diluted with the dialysate effluent, in a manner that imitates the in vivo changes in these solutions during their intraperitoneal dwell.

Effect of Peritoneal Dialysis Solution on the Antimicrobial Activity of Cephalosporins

We studied the effect of peritoneal dialysis solution (PDS) on the antibacterial activity of seven cephalosporins, gentamicin, tobramycin and amikacin. The six bacterial species employed in the study survived in a wide range of concentrations of PDS, however, Staphylococcus aureus did not survive beyond 24 h in PDS. There were no physical incompatibilities between any of the antibiotics and PDS. None of the cephalosporins was bactericidal in PDS, whereas, the bactericidal concentrations of the aminoglycosides in PDS approximated those of aminoglycosides in broth. We conclude from these in vitro data that cephalosporins may not be ideal agents for intraperitoneal therapy when they are administered in PDS.

Human plasma and the antibacterial effect of peritoneal dialysis solutions.

The influence of human plasma on the antibacterial effect of solutions for peritoneal dialysis was studied. The solutions contained 43 mEq per litre of either acetate or lactate as the source of base. Enough pooled human plasma was added to half of each solution to give a total concentration of a gramme of protein per litre. The numbers of viable organisms from 15 clinical isolates each of Staphylococcus aureus, Escherichia coli, and Pseudomonas species were counted before and after incubation in the four solutions. Numbers of viable Staph. aureus and E. coli diminished consistently after incubation in all four solutions, but the greatest decreases occurred in the acetate solution which contained no plasma. Plasma abolished the greater antibacterial effect of acetate on these organisms. Differences between numbers of viable Pseudomonas sp. after incubation in the four solutions were not significant. The diffusion of substances from plasma into dialysis fluids during peritoneal dialysis, therefore, may abolish the greater antibacterial effect of solutions made with acetate rather than lactate.