Frequent Complication Of Peritoneal Dialysis Research Articles

An investigation into the correlation between intraperitoneal teicoplanin concentrations and treatment outcomes in peritoneal dialysis-associated peritonitis.

Peritoneal dialysis-associated peritonitis (PDAP) is a frequent complication of peritoneal dialysis. The guidelines from the International Society for Peritoneal Dialysis (ISPD) suggest administering teicoplanin through the peritoneal route to treat PDAP, but do not specify the ideal concentration for peritoneal dialysis effluent (PDE). Patients meeting the trial criteria for PDAP in our hospital between July 2022 and December 2023 were enrolled. Data on PDE white blood cell count, PDE neutrophil percentage, clinical symptoms, CRP, and PCT were gathered pre- and post-treatment. Incidences of adverse drug reaction (ADR) and case numbers during treatment were recorded. Subsequently, patients were categorized into cured and uncured groups for evaluating the relationship between PDE teicoplanin concentration and treatment effectiveness. The self-control study results on teicoplanin efficacy indicated intraperitoneal teicoplanin administration achieved an efficacy rate of 88.9% and an ADR incidence of 5.5% in treating PDAP patients. There was no observed correlation between teicoplanin blood concentration and PDE concentration. PDE teicoplanin concentrations on days 1, 3, 5, and 7 post-dosing were higher inthe cured group, with a significant contrast in PDE concentration on day 5 between the 18.98 ± 2.43mg/L of the cured group and the 12.07 ± 2.68mg/L of the uncured group. ROC curve revealed a higher likelihood of cure in patients when PDE teicoplanin concentration exceeded 15.138mg/L on day 5 post-dosing. Univariate and multifactorial studies identified 24-h urine volume and the number of daily abdominal dialysis sessions as influential factors in PDE teicoplanin concentration on day 5. A positive correlation was found between 24-h urine volume and PDE teicoplanin concentration, with PDAP patients having urine volume over 537mL showing significantly higher drug concentrations. Conversely, the number of daily PDAP sessions was negatively correlated with PDE teicoplanin concentrations, indicating that patients with 1∼3 daily PDAP sessions had notably higher PDE teicoplanin concentrations compared to those with 4∼6 sessions. Therefore, PDAP patients who use intraperitoneal teicoplanin could effectively control infection by monitoring the PDE teicoplanin concentration (>15.138mg/L) on day 5 after dosing.

Candida guilliermondii Peritonitis During Peritoneal Dialysis. Case Report and Literature Review

Peritonitis is the most frequent complication of peritoneal dialysis (PD) and 3–6% of episodes have fungal origin. Candida guilliermondii is an uncommon species of Candida with invasive behavior in patients affected by severe underlying disorders or using indwelling vascular devices.Here we report the case of an 84-year-old woman undergoing outpatient PD for 4 years who had fever, chills, and diffuse increasing abdominal pain. After empiric antimicrobial therapy, based on teicoplanin in the dialytic circuit plus oral ciprofloxacin plus fluconazole, the patient was hospitalized. Afterwards, the culture from the peritoneal fluid showed the presence of C. guilliermondii.PD-related fungal peritonitis is an infrequent event, but the morbidity and mortality rates are significant. In this scenario, appropriate prevention strategies including antifungal prophylaxis during antibiotic treated bacterial peritonitis should be evaluated.

Connection assist devices for peritoneal dialysis.

Patients with kidney failure who require kidney replacement therapy (KRT) have been increasing globally. Home-based therapies, such as peritoneal dialysis (PD), allow patients to undergo KRT in the home environment, alleviating treatment costs, patient transport, and hospital admission. Peritoneal dialysis-related peritonitis is still the most frequent complication of PD and is often related to technique failure, which can result in PD failure, transfer to hemodialysis, or mortality. The cause of technique failure is multifactorial, and a portion of technique failure is due to underlying physical or cognitive disabilities. There are several connection devices that have been developed to reduce CAPD-related peritonitis. These connection devices are reviewed in this article.

Point-of-care ultrasound in peritoneal dialysis catheter-related infection: An observational study

Point-of-care ultrasound aims to enhance physical examination findings with real-time information from the ultrasound. Peritoneal dialysis catheter-related infections are a frequent complication of peritoneal dialysis and a major predisposing factor to peritonitis. The diagnosis of peritoneal dialysis catheter-related infections is made with physical examination, but physical findings usually lack sensitivity or specificity. This is a single-center observational study that aimed to evaluate the accuracy of point-of-care ultrasound for the diagnosis of peritoneal dialysis catheter-related infections. Sixteen peritoneal dialysis patients with peritoneal dialysis catheter-related infections clinical suspicion were enrolled in this study, as well as nine controls. Peritoneal dialysis catheter-related infection was defined as a purulent discharge with or without inflammatory signs in the peritoneal dialysis catheter exit-site or subcutaneous tunnel, and a positive microbiological culture collected from the exit-site. Point-of-care ultrasound was considered positive when an anechoic collection in relation to the external cuff or catheter tunnel was identified. Physical examination findings were coded using the Exit-site Scoring System. A total of 13 peritoneal dialysis catheter-related infections were diagnosed. The mean Exit-site Scoring System score for the suspected cases of peritoneal dialysis catheter-related infections was 2,82 ± 1,22, and the most commonly encountered sign was purulent discharge. All of the cases of peritoneal dialysis catheter-related infections had a positive point-of-care ultrasound. In contrast, none of the controls had a positive point-of-care ultrasound (p < 0,001). The area under the receiver operating characteristic curve of physical examination for the diagnosis of peritoneal dialysis catheter-related infections was 0,6 (95% CI 0,37-0,84). In contrast, point-of-care ultrasound had an AUROC of 0,91 (95% CI: 0,73-1) for the diagnosis of peritoneal dialysis catheter-related infections. Nephrologist-performed point-of-care ultrasound is feasible and superior to physical examination for the diagnosis of peritoneal dialysis catheter-related infections.

The ideal position of the peritoneal dialysis catheter is not always ideal.

Peritoneal catheter dysfunction is a frequent complication of peritoneal dialysis (PD). Traditionally, dysfunction has been attributed to catheter malposition, but whether the location of the catheter tip in the small pelvis really determines proper function is unclear. We reviewed 900 abdominal X-ray images of PD patients from a 7-year period in two PD units that use different catheter types (straight and Swan Neck Curled). In 52% of the images, the dialysis catheter tip was located in the ideal position in the small pelvis and in 48% in other sites. Peritoneal catheter function was normal at the time of imaging in 87% of those with ideal catheter tip position, and in 74% of those with other than ideal position. The tip was located in small pelvis in 35% of images performed during catheter dysfunction and in 56% of those performed during normal catheter function. There were no differences between two catheter types. The positive predictive value of abdominal X-ray images to predict catheter function was 26%, and the negative predictive value 87%. We also found a significant positive correlation between polycystic kidney disease and normal catheter function. In contrast, obese patients were more likely to have catheter malfunction. Previous abdominal surgery was not associated with catheter dysfunction. Our data showed a higher probability of normal function of peritoneal catheters whose tips were located in the small pelvis. However, also malpositioned catheters generally functioned well, and malpositioning of the PD catheter did not in itself explain its malfunction.

Association between causes of peritoneal dialysis technique failure and all-cause mortality

Technique failure is a frequent complication of peritoneal dialysis (PD), but the association between causes of death-censored technique failure and mortality remains unclear. Using Australian and New Zealand Dialysis and Transplant (ANZDATA) registry data, we examined the associations between technique failure causes and mortality in all incident PD patients who experienced technique failure between 1989–2014. Of 4663 patients, 2415 experienced technique failure attributed to infection, 883 to inadequate dialysis, 836 to mechanical failure and 529 to social reasons. Compared to infection, the adjusted hazard ratios (HR) for all-cause mortality in the first 2 years were 0.83 (95%CI 0.70–0.98) for inadequate dialysis, 0.78 (95%CI 0.66–0.93) for mechanical failure and 1.46 (95%CI 1.24–1.72) for social reasons. The estimates from the competing risk models were similar. There was an interaction between age and causes of technique failure (pinteraction < 0.001), such that the greatest premature mortality was observed in patients aged >60 years post social-related technique failure. There was no association between causes of technique failure and mortality beyond 2 years. In conclusion, infection and social-related technique failure are associated with premature mortality within 2 years post technique failure. Future studies examining the associations may help to improve outcomes in these patients.

A pathogenetic role for M1 macrophages in peritoneal dialysis-associated fibrosis

Peritoneal fibrosis (PF) is a frequent complication of peritoneal dialysis (PD) accompanied by the infiltration of inflammatory cells. Recently, the function of macrophages in an inflammatory microenvironment during PD remains unknown. This study aimed to elucidate the role of distinct macrophage phenotypes in the progression of PF through macrophage depletion in a peritoneal dialysis-induced mouse model. After injection of 200 μl liposomal clodronate (LC) at the start of instillation PD fluids (PDFs), mice were injected with 100 μL LC every 4 days after the first time injection for longer macrophage depletion, while control mice were co-treated with PBS liposomes. For macrophages transfusion,primary macrophages (M0) were stimulated into M1 and M2 macrophages and transfuritoneal fibrosis (PF) is a frequent complication of peritoneal dialysis (PD) accompanied by the infiltration of inflammatory cells. Recently, the function of macrophages in an inflammatory microenvironment during PD remains unknown. This study aimed to elucidate the role of distinct macrophage phenotypes in the progression of PF through macrophage depletion in a peritoneal dialysis-induced mouse model. After injection of 200 μl liposomal clodronate (LC) at the start of instillation PD fluids (PDFs), mice were injected with 100 μL LC every 4 days after the first time injection for longer macrophage depletion, while control mice were co-treated with PBS liposomes. For macrophages transfusion,primary macrophages (M0) were stimulated into M1 and M2 macrophages and transfused into the mice the next day after each LC injection. Mice were sacrificed after 6 weeks of PDFs treatment for the assessment of histological changes, ECM deposition and peritoneal ultrafiltration function. Systemic monocyte/macrophage depletion resulted in less severe structural alterations, including thickening and cubic transformation of mesothelial cells, fibrin deposition, fibrous capsule formation, and interstitial fibrosis. A strong reduction of alpha-smooth muscle actin (α-SMA) and fibronectin expression, as well as an increased E-cadherin expression was also observed, indicating an overall inhibition of peritoneal fibrosis in macrophages depletion mice.M1 macrophage reperfusion showed a significant increase in histological damages, ECM deposition and peritoneal ultrafiltration functional decline compared with those of the M2 and control groups. TLR4 expression was enhanced in M1 macrophage-treated group. These results suggest that M1 macrophages are an important mediator of peritoneal fibrosis.

Clinical and microbiological aspects of peritonitis associated with peritoneal dialysis in adult patients with chronic renal failure in the Emergency Department

Peritonitis is the most important and frequent complication of peritoneal dialysis (PD). Bacterial infections are responsible in most cases, with characteristic symptoms. To determine the most frequent pathogens in peritonitis associated with PD in patients with chronic renal failure (CRF). Methodos: Retrospective, descriptive, cross-sectional and observational study of patients with peritonitis in PD with CRF of the emergency department, between July 2012 and June 2013. Sociodemographic, diagnostic, clinical and microbiological and cellular data were evaluated from the patient's fluid. Dialysis. From 73 reviewed records, 52% were male. The primary cause of CRF was diabetes mellitus type 2 (67%). Symptoms presented: abdominal pain (86%), vomiting (42%) and nausea (34%), with anemia, azotemia, hyperglycemia, hypoalbuminemia and hyponatremia. The positive microbiological cultures were 59%; and the pathogens identified were Candida tropicalis (9.6%), Staphylococcus epidermidis (8.2%), Enterococcus faecalis and Staphylococcus haemolyticus (6.8% each one), associated with elevated leukocytes, azotemia and high cellularity in peritoneal fluid (p <0.05). The main microorganism determined was of fungal origin associated with leukocytes, azotemia and high cellularity.

Prominent Levels of the Profibrotic Chemokine CCL18 during Peritonitis: In Vitro Downregulation by Vitamin D Receptor Agonists.

Peritoneal dialysis (PD) is used as a renal replacement therapy, which can be limited by peritoneal membrane ultrafiltration failure (UFF) secondary to fibrotic processes. Peritonitis, a frequent complication of PD, is a major risk factor for peritoneal membrane fibrosis and UFF. Low peritoneal levels of the chemokine CCL18 are associated with preservation of peritoneal membrane function in PD. Given that CCL18 is involved in fibrotic processes and recurrent peritonitis, it is a risk factor for peritoneal membrane failure; thus, we evaluated CCL18 concentrations in peritoneal effluents from patients undergoing peritonitis episodes. Pharmacological interventions aimed at diminishing the production of CCL18 were also explored. Fivefold higher CCL18 peritoneal concentrations were found during acute bacterial peritonitis, in parallel with the increased infiltration of macrophages. Unexpectedly, CCL18 was also highly (50-fold) increased during sterile eosinophilic peritonitis, and peritoneal eosinophils were found to express CCL18. In vitro treatment of peritoneal macrophages with the vitamin D receptor agonist paricalcitol was able to reduce the secretion and the expression of CCL18 in isolated peritoneal macrophages. In conclusion, our study suggests that the chemokine CCL18 can be a mediator of peritoneal membrane failure associated with peritonitis episodes as well as providing a new potential therapeutic target.

The Role of TLR4 in M1 Macrophage-Induced Epithelial-Mesenchymal Transition of Peritoneal Mesothelial Cells

Background/Aims: Peritoneal fibrosis is a frequent complication of peritoneal dialysis that follows inflammation. It is recognized that epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs), plays a key role in fibrogenesis. However, the relationship between inflammatory macrophages and PMCs remains elusive. In this study, we investigated the effects of different polarized macrophages on EMT of HMrSV5 PMCs. Methods: Monocytes were polarized to M1/M2 macrophages before being added to HMrSV5 in direct or indirect contact. Morphological changes of HMrSV5 were observed and toll-like receptors 4 (TLR4) on macrophage surfaces was detected using flow cytometry. EMT markers and intracellular signals of HMrSV5 cells were assessed using real time-PCR and WB. Results: The typical epithelial cell morphology of HMrSV5 disappeared after co-culture with M1 macrophages and was accompanied by decreased E-cadherin and increased α-SMA, suggesting HMrSV5 undergo EMT. These effects depended on direct contact between the two cells, as indirect contact or co-culture with M2 macrophages had no effect. Intriguingly, we found TLR4 surface receptors were activated on sorted M1 cells in co-culture, and related signal adaptors, such as TRIF, were obviously upregulated. Conclusion: Direct contact with M1 macrophages induces EMT of PMCs, during which TRIF-dependent TLR4 signaling pathway was activated.

Migration of an intrauterine device and peritonitis in a peritoneal dialysis patient

Peritonitis is a frequent complication of peritoneal dialysis. Infection is most commonly introduced into the peritoneal cavity through the indwelling catheter during the dialysis procedure. Occasionally peritonitis is associated with underlying abdominal pathology rather than secondary to the dialysis procedure itself. Here we present a case of polymicrobial peritonitis in a patient on automated peritoneal dialysis (APD) in the setting of uterine perforation by an intrauterine device (IUD). Clinicians involved in the care of patients on peritoneal dialysis should remain vigilant for underlying abdominal pathology in cases of complicated peritonitis.

Inhibition of Transforming Growth Factor-Activated Kinase 1 (TAK1) Blocks and Reverses Epithelial to Mesenchymal Transition of Mesothelial Cells

Peritoneal fibrosis is a frequent complication of peritoneal dialysis following repeated low grade inflammatory and pro-fibrotic insults. This pathological process may lead to ultrafiltration failure and eventually to the discontinuing of the therapy. Fibrosis is linked to epithelial to mesenchymal transition (EMT) of the peritoneal mesothelial cells, which acquire invasive and fibrogenic abilities. Here, we analyzed the role of the transforming growth factor-activated kinase-1 (TAK1) in the EMT of primary mesothelial cells from human peritoneum. The inhibition of TAK1 in mesenchymal-like mesothelial cells from the effluents of patients undergoing peritoneal dialysis led to the reacquisition of the apical to basolateral polarity, to increased expression of epithelial and to down-regulation of mesenchymal markers. TAK1 inhibition also resulted in decreased migratory/invasive abilities of effluent-derived mesothelial cells. Simultaneous inhibition of ERK1/2 and TAK1 pathways did not lead to an additive effect in the reacquisition of the epithelial phenotype. Inhibition of TAK1 also blocked EMT in vitro and reduced the levels of PAI-1, which is involved in fibrosis and invasion. Analysis of signalling pathways downstream of TAK1 involved in EMT induction, showed that TAK1 inhibition reduced the transcriptional activity of NF-κB and Smad3, as well as the phosphorylation of c-jun, while enhancing Smad1–5–8 activity. These results demonstrate that TAK1 is a cross-point in a network including different pro-EMT transcription factors, such as NF-κB, Snail, AP-1 and Smads. The identification of TAK1 as a main biochemical mediator of EMT and fibrosis in mesothelial cells from human peritoneum and the study of signalling pathways induced by its activity may be relevant in the design of new therapies aimed to counteract peritoneal fibrosis.

Unusual presentation of peritonitis with persistent clear aspirate: a case report

IntroductionPeritonitis is the most frequent complication of peritoneal dialysis. Diagnosis of peritonitis includes symptoms and signs of peritonitis with a cloudy aspirate of more than 100 WBC/ml, as well as positive cultures. Although sterile peritonitis has been reported in the literature, to the best of our knowledge this is the first report of an unusual presentation of peritonitis without any white blood cells in the peritoneal aspirate despite multiple positive peritoneal cultures.Case presentationAn 82-year-old Caucasian man who had been on continuous cycling peritoneal dialysis for 12 years was admitted to our hospital with general malaise, loss of appetite, weight loss and somnolence. He did not describe abdominal pain or fever. Even though his peritoneal fluid was consistently negative for leukocytes and clear, he had peritonitis with different organisms consecutively.ConclusionsOur case report shows that any patient on peritoneal dialysis presenting with evidence of infection (fever, peripheral leukocytosis) without an obvious cause should have aspirate cultures done even if the aspirate is clear and abdominal pain is absent. Our case report may change the initial work-up and management of these patients. We believe this report is of interest to general medicine and emergency room physicians as well as nephrologists.

Peritonitis in children on peritoneal dialysis in Cape Town, South Africa: epidemiology and risks

Peritonitis is a frequent complication of peritoneal dialysis (PD) in children as well in adults. Data on PD and peritonitis in pediatric patients are very scarce in developing countries. A retrospective cohort study was performed between 2000 and 2008 with the aim to evaluate PD treatment and peritonitis epidemiology in pediatric patients in South Africa and identify risk factors for peritonitis. Baseline characteristics and potential risk factors of peritonitis were recorded, including housing, socio-economic circumstances, distance to PD center, type of PD, mode of catheter placement, race, presence of gastrostomy tube, weight, and height. Outcome indices for peritonitis were peritonitis rate, time to first peritonitis, and number of peritonitis-free patients. The patient cohort comprised 67 patients who were on PD for a total of 544 months. The total number of peritonitis episodes was 129. Median peritonitis rate was one episode every 4.3 patient months (2.8 episodes/patient-year, range 0–21.2). Median time to first infection was 2.03 months (range 0.1–21.5 months), and 28.4% of patients remained free from peritonitis. Patients with good housing and good socio-economic circumstances had a significantly lower peritonitis rate and a longer time to first peritonitis episode. Peritonitis rate was high in this cohort, compared to numbers reported for the developed world; the characteristics of causative organisms are comparable. The most important risk factors for the development of peritonitis were poor housing and poor socio-economic circumstances. More intensive counseling may be beneficial, but improvement of general socio-economic circumstances will have the greatest influence on PD success.

Peritoneal dialysis-related peritonitis: an analysis of risk factors in Northeast Anatolia*

Peritonitis is almost the most frequent complication of peritoneal dialysis (PD). Besides being the most frequent reason of hospitalization, peritonitis is also the most important determining factor of mortality-morbidity and technique survival among PD patients. In this study, it was aimed to identify the risk factors for peritonitis in these patients. Materials and methods: In this clinical cohort, records of 218 patients were collected between January 1998 and December 2007. The patients’ demographic, clinical, and laboratory parameters were recorded. Results were analyzed to compare patients who never had peritonitis and patients with at least one episode of peritonitis. Independent predictors of peritonitis were assessed using Cox regression, and the hazard ratio (HR) was determined using 95% confidence interval (95% CI). Results: Of over 6304 patient-months, 337 episodes of peritonitis were observed. The overall peritonitis rate was 0.64 attack/year. The risk of peritonitis was lower for PD patients with each 1 g/dL increase in mean albumin levels (HR, 0.39; 95% CI, 0.24-0.65; P < 0.001). Variables identified to be associated with an increased likelihood of peritonitis were: the placement of catheter via surgery (HR, 3.97; 95% CI, 2.16-7.29; P < 0.001), constipation (HR, 2.22; 95% CI, 1.26-3.92; P < 0.01), and amyloidosis (HR, 1.81; 95% CI, 0.93-3.50; P = 0.078). Conclusion: Hypoalbuminemia, constipation, the placement of catheter via surgery, and amyloidosis were found to increase the risk of peritonitis in the present study. Such risk factors should be kept in mind during follow-up of patients under PD.

Nitric oxide synthase isoforms play distinct roles during acute peritonitis

Background. Acute peritonitis is the most frequent complication of peritoneal dialysis (PD). Increased nitric oxide (NO) release by NO synthase (NOS) isoforms has been implicated in acute peritonitis, but the role played by the NOS isoforms expressed in the peritoneum is unknown.Methods. We investigated the structural and functional consequences of acute peritonitis induced by LPS in wild-type (WT) mice versus knockout mice (KO) for the endothelial NOS (eNOS), the inducible NOS (iNOS) or the neuronal NOS (nNOS).Results. The level of NO metabolites (NOx) in the dialysate was maximal 18 h after LPS injection. LPS induced a significant increase in the transport of small solutes and decreased ultrafiltration in WT mice. These changes, which occurred without vascular proliferation, were paralleled by the upregulation of nNOS and eNOS, and the induction of iNOS. The transport modifications induced by LPS were significantly reversed in eNOS KO mice, but not modified in mice lacking iNOS or nNOS. In contrast, the increase of dialysate NOx was abolished in iNOS KO mice and significantly reduced in eNOS KO mice, but left unchanged in mice lacking nNOS. Mice lacking iNOS also showed more severe inflammatory changes, and a trend towards increased mortality following LPS.Conclusion. These data demonstrate specific roles for NOS isoforms in the peritoneal membrane and suggest that selective eNOS inhibition may improve peritoneal transport during acute peritonitis.

Dialysis-associated peritonitis in children.

Peritonitis remains a frequent complication of peritoneal dialysis in children and is the most common reason for technique failure. The microbiology is characterized by a predominance of Gram-positive organisms, with fungi responsible for less than 5% of episodes. Data collected by the International Pediatric Peritonitis Registry have revealed a worldwide variation in the bacterial etiology of peritonitis, as well as in the rate of culture-negative peritonitis. Risk factors for infection include young age, the absence of prophylactic antibiotics at catheter placement, spiking of dialysis bags, and the presence of a catheter exit-site or tunnel infection. Clinical symptoms at presentation are somewhat organism specific and can be objectively assessed with a Disease Severity Score. Whereas recommendations for empiric antibiotic therapy in children have been published by the International Society of Peritoneal Dialysis, epidemiologic data and antibiotic susceptibility data suggest that it may be desirable to take the patient- and center-specific history of microorganisms and their sensitivity patterns into account when prescribing initial therapy. The vast majority of patients are treated successfully and continue peritoneal dialysis, with the poorest outcome noted in patients with peritonitis secondary to Gram-negative organisms or fungi and in those with a relapsing infection.

Inhibition of Nitric Oxide Synthase Reverses Permeability Changes in a Mouse Model of Acute Peritonitis

Acute peritonitis is the most frequent complication of peritoneal dialysis. Previous studies have suggested a major role for nitric oxide (NO) in the permeability changes and loss of ultrafiltration induced by acute peritonitis. In this study, we further investigated the potential role of NO in a mouse model of peritonitis induced by Escherichia coli Lipopolysaccharide (LPS). A 2-hour peritoneal equilibration test was performed in control and LPS-treated mice using 7% glucose dialysate supplemented or not with the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). The levels of NO metabolites in the dialysate were maximal 18 hours after LPS injection. At that time, acute peritonitis induced by LPS was reflected by an increased recruitment of leukocytes, an increased intraperitoneal release of interleukin-6, a significant increase in the peritoneal permeability for small solutes, a loss of sodium sieving, and a loss of ultrafiltration in comparison with controls. Addition of L-NAME in LPS-treated mice significantly reversed permeability modifications and prevented the release of NO metabolites into the dialysate. These results confirm that increased NO mediates permeability modifications during acute peritonitis, and illustrate the potential of mouse models to investigate the molecular mechanisms regulating peritoneal permeability.

Inhibition of nitric oxide synthase reverses changes in peritoneal permeability in a rat model of acute peritonitis

Acute peritonitis is the most frequent complication of peritoneal dialysis (PD), and nitric oxide (NO) is thought to play a role in the structural and permeability changes observed in this condition. We have used a combination of expression, enzymatic and pharmacological studies to substantiate the potential role(s) played by NO during peritonitis. The peritoneal equilibration test was performed in control rats and rats with acute peritonitis (originating from skin flora), using standard dialysate supplemented or not with the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). In parallel, peritoneal NOS enzymatic activities were measured and expression studies for NOS isoforms and S-nitrosocysteine reactivity performed in the peritoneum. In comparison with controls, rats with acute peritonitis were characterized by inflammatory changes, increased S-nitrosocysteine immunoreactivity, and increased NOS activities in the peritoneum, due to the up-regulation of endothelial and inducible NOS. In parallel, rats with acute peritonitis showed increased permeability for small solutes; decreased sodium sieving; loss of ultrafiltration (UF); and increased protein loss in the dialysate. Addition of L-NAME to the dialysate did not induce permeability changes in control rats, but significantly improved UF and reversed permeability modifications in rats with peritonitis. The effect of L-NAME was reflected by a mild but consistent increase in blood pressure during PD exchange. Our results demonstrate that local generation of NO, secondary to up-regulation of NOS isoforms, plays an important role in the regulation of peritoneal permeability during acute peritonitis in rats. By itself, NOS inhibition improves UF and reverses permeability changes, which might offer new therapeutic perspectives in acute peritonitis.

Fungal Peritonitis in Peritoneal Dialysis: Our Experience and Review of Treatments

From January 1975 to April 1982, 10 of our patients undergoing chronic peritoneal dialysis developed fungal peritonitis. Of six treated without removing the catheter two survived after intraperitoneal (IP) administration of imidazole derivatives, and four died despite combined IP and intravenous (IV) therapy. Of four patients treated by catheter removal, all survived, two without any additional therapy and two after IV antifungal treatment. Three of the deaths followed cardiac or cerebral accidents, while one was related to Candida sepsis. Bacterial peritonitis is a frequent complication of peritoneal dialysis (FD). In addition fungal peritonitis has been reported with increasing frequency with the growing diffusion of FD, the subsequent increase in infectious episodes, the antibiotic treatment, which such complications require and the improvement in technique for mycological diagnosis. This paper describes our experience with the clinical manifestations of fungal peritonitis and its treatment in 10 patients undergoing intennittent peritoneal dialysis (IFD) or continuous ambulatory peritoneal dialysis (CAFD).