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[Peritonitis in continuous ambulatory peritoneal dialysis. Culture of peritoneal dialysate fluid].

Conventional aerobic and anaerobic culture of peritoneal dialysate effluent from patients in continuous peritoneal dialysis (CAPD) was compared to culture in a semiautomated blood culture system. During a two-year period 78 of 79 consecutive episodes of peritonitis among 45 Danish CAPD patients were cultured and the etiology of the infection found in 73 (94%). The sensitivity of the blood culture system was 88%, whereas the sensitivity of the conventional culture of the dialysate effluent was 81%. This difference is not significant (McNemar test; 0.5 > p > 0.3). The majority of isolates were Gram-positive bacteria dominated by coagulase-negative staphylococci (38%). In comparison, only 2% of the cultures of peritoneal dialysate effluent taken within the same period from patients without clinical signs of peritonitis were positive. All the Gram-positive aerobic bacteria were sensitive to vancomycin whereas 97% of the Gram-negative aerobic bacteria were sensitive to gentamicin. An initial empiric treatment of peritonitis with a combination of vancomycin and gentamicin is recommended.

Adolescent↗

Advanced glycation end-products in the peritoneal fluid and in the peritoneal membrane of continuous ambulant peritoneal dialysis patients.

In patients on continuous ambulant peritoneal dialysis (CAPD) treatment, the peritoneal membrane is continuously exposed to the high glucose concentration contained in the dialysate. This may lead to the local generation of advanced glycation end-products (AGEs). To test this hypothesis we evaluated the plasma and dialysate AGE concentrations in five CAPD patients. The dialysate was measured after a 1 h and after a 12 h dwell time. Additionally, in two patients an immunohistochemical investigation of the peritoneal membrane for AGE was performed. For the determination of AGE an ELISA using a polyclonal antibody against AGE bovine serum albumin was used; the immunohistochemical staining was performed using the streptavidin-biotin complex method. We found only low concentrations of AGE in the dialysate after a 1 h dwell time; after 12 h, however, the dialysate AGE was even greater than the plasma concentration. In both peritoneal specimens we found positive staining for AGE in the interstitium of the mesothelial layer. The dialysate AGE contained a high proportion of high-molecular-weight AGE proteins and low-molecular-weight AGE was found to be in the same concentration range as the total serum AGE. We conclude that there is local generation of AGE in the peritoneal membrane and a 'washing out' of AGE from the peritoneal membrane during longer dwell times. We speculate that the accumulation of AGE might lead to some of the functional and morphological alterations observed after long-term CAPD.

Adult↗

Peritoneal transport properties and dialysis dose affect growth and nutritional status in children on chronic peritoneal dialysis. Mid-European Pediatric Peritoneal Dialysis Study Group.

To evaluate a possible effect of peritoneal transport properties and dialysis dose on the physical development of children on chronic peritoneal dialysis, a cohort of 51 children was prospectively followed for 18 mo. Peritoneal transport characteristics were assessed by serial peritoneal equilibration tests (PET), dialysis efficacy by dialysate and residual renal clearance measurements, and growth and nutritional status by the longitudinal changes (delta) of height SD score (SDS), body mass index (BMI) SDS, and serum albumin. delta height SDS was negatively correlated with the creatinine equilibration rate observed in the initial PET (r = -0.31, P < 0.05). Multiple regression analysis confirmed the negative effect of the high transporter state (partial r2 = 0.07), and disclosed an additional positive effect of dialytic C(Cr) (partial r2 = 0.11) and a weak negative effect of daily dialysate volume (partial r2 = 0.04) on delta height SDS. delta BMI SDS was strongly age-dependent (r = -0.48, P < 0.001); while relative body mass gradually increased below 4 yr of age, it remained stable in older children. Positive changes in BMI SDS were associated with rapid PET creatinine equilibration rates (univariate r = 0.35, P < 0.05) and/or large dialysate volumes (multivariate partial r2 = 0.11), suggesting a role of dialytic glucose uptake in the development of obesity. The change in serum albumin concentrations was positively correlated with dialysate volume (partial r2 = 0.14), and negatively affected by dialytic protein losses (partial r2 = 0.06). In conclusion, the peritoneal transporter state is a weak but significant determinant of growth and body mass gain in children on chronic peritoneal dialysis. Rapid small solute equilibration contributes to impaired growth but enhanced acquisition of body mass. Dialytic small solute clearance has a weak positive effect on statural growth independent of the transporter state, but does not affect body mass gain.

Adolescent↗

Increased peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients. The Canada-USA (CANUSA) Peritoneal Dialysis Study Group.

The objective of this study was to evaluate the association of peritoneal membrane transport with technique and patient survival. In the Canada-USA prospective cohort study of adequacy of continuous ambulatory peritoneal dialysis (CAPD), a peritoneal equilibrium test (PET) was performed approximately 1 mo after initiation of dialysis; patients were defined as high (H), high average (HA), low average (LA), and low (L) transporters. The Cox proportional hazards method evaluated the association of technique and patient survival with independent variables (demographic and clinical variables, nutrition, adequacy, and transport status). Among 606 patients evaluated by PET, there were 41 L, 192 LA, 280 HA, and 93 H. The 2-yr technique survival probabilities were 94, 76, 72, and 68% for L, LA, HA, and H, respectively (P = 0.04). The 2-yr patient survival probabilities were 91, 80, 72, and 71% for L, LA, HA, and H, respectively (P = 0.11). The 2-yr probabilities of both patient and technique survival were 86, 61, 52, and 48% for L, LA, HA, and H, respectively (P = 0.006). The relative risk of either technique failure or death, compared to L, was 2.54 for LA, 3.39 for HA, and 4.00 for H. The mean drain volumes (liters) in the PET were 2.53, 2.45, 2.33, and 2.16 for L, LA, HA, and H, respectively (P < 0.001). After 1 mo CAPD treatment, the mean 24-h drain volumes (liters) were 9.38, 8.93, 8.59, and 8.22 for L, LA, HA, and H, respectively (P < 0.001); the mean 24-h peritoneal albumin losses (g) were 3.1, 3.9, 4.3, and 5.6 for L, LA, HA, and H, respectively (P < 0.001). The mean serum albumin values (g/L) were 37.8, 36.2, 33.8, and 32.8 for L, LA, HA, and H, respectively (P < 0.001). Among CAPD patients, higher peritoneal transport is associated with increased risk of either technique failure or death. The decreased drain volume, increased albumin loss, and decreased serum albumin concentration suggest volume overload and malnutrition as mechanisms. Use of nocturnal cycling peritoneal dialysis should be considered in H and HA transporters.

Adult↗

On the origin of peritoneal resident macrophages. II. Recovery of the resident macrophage population in the peritoneal cavity and in the milky spots after peritoneal cell depletion.

A kinetic study of the resident macrophage population in the peritoneal cavity and in the milky spots was done in mice depleted of peritoneal cells by repeated peritoneal washing. According to the distribution of the peroxidatic activity, four types of peritoneal macrophages could be distinguished. The size of each of these subpopulations depends on the length of the interval after peritoneal-cell depletion. Tritiated thymidine experiments revealed in the peritoneal cavity and in the milky spots local DNA synthesis by resident and PO-negative macrophages but not by monocytes or exudate macrophages and exudate/resident macrophages. The relationships between the various types of macrophages are discussed. No evidence was found for a relationship between resident macrophages and monocytes or macrophages with PO-positive granules. The PO-negative macrophage population was suggested to be heterogeneous, part of it being derived from monocytes and part having a relationship with the resident macrophages.

Animals↗

Regulation of differentiation of peritoneal B-1a (CD5+) B cells. Activated peritoneal macrophages release prostaglandin E2, which inhibits IgM secretion by peritoneal B-1a cells.

The B-1a (CD5+) subset of B cells comprises the majority of B cells in the peritoneal cavity and is implicated in the pathogenesis of certain autoimmune diseases and lymphoproliferative disorders. When we stimulated purified B-1a cells with LPS, they produced more than four times as much IgM as similarly stimulated whole peritoneal cells (containing the same number of B-1a cells). Reconstitution experiments using FACS-purified peritoneal cell populations revealed that resident peritoneal macrophages (Mac1+, B220-) profoundly inhibited the LPS response of peritoneal B-1a cells. Culture of B-1a cells with peritoneal macrophages at a ratio of 3:1 (reflecting the in vivo ratio) resulted in a fivefold or greater reduction in the IgM response to LPS. LPS activation of macrophages resulted in production of a soluble factor that inhibited LPS-induced B cell differentiation by 86% when used at a concentration of 5%. When [3H]arachidonic acid-pulsed macrophages were stimulated with LPS, the major arachidonic acid metabolite secreted was PGE2 (a potent inhibitor of B cell differentiation). The inhibitory capacity of the macrophage-derived supernatant was reversed by the addition of anti-PGE2. These findings indicate that macrophage-derived PGE2 functions as an important regulator of polyclonal response of B-1a cells to LPS.

Animals↗

[Peritoneal blood flow and peritoneal transfer parameters during intermittent peritoneal dialyses performed with administration of sodium nitroprusside or chlorpromazine].

Effective peritoneal capillary blood flow (EPBF) was evaluated by calculation of diffusive mass transport coefficient of CO2 during intermittent peritoneal dialysis performed with intraperitoneal administration of sodium nitroprusside (NP, 5 mg/l of dialysis solution) or chlorpromazine (Cl-Prom, 2.5 mg/l of dialysis solution). Peritoneal transfer rates of substances of different molecular size and charge were simultaneously examined and compared with EPBF. During NP or Cl-Prom administration, EPBF was respectively 220 +/- 40 (n = 11) and 224 +/- 29 (n = 10) ml/min. These values were insignificantly higher than those obtained during dialyses without drugs (169 +/- 16 ml/min, n = 10). NP and Cl-Prom did not cause any significant changes in peritoneal transfer of CO2. Transfer rates of HCO3 and tCO2 were increased only with NP. Both drugs enhanced peritoneal removal of Na+, K+, urea, uric acid and total protein, but with similar EPBF during the use of both drugs, the effect of NP was more pronounced. The obtained results indicate that EPBF is not a major factor responsible for enhanced peritoneal transfer rates during dialyses performed with NP or Cl-Prom.

Carbon Dioxide↗

The response of human peritoneal macrophages to stimulation with bacteria isolated from episodes of continuous ambulatory peritoneal dialysis-related peritonitis.

The metabolism of arachidonic acid, by isolated peritoneal macrophages in response to stimulation with microorganisms isolated from continuous ambulatory peritoneal dialysis (CAPD) patients, is not specific to the individual strain but is determined by species. Isolates of Staphylococcus aureus (n = 7) and Staphylococcus epidermidis (n = 13) produced a significant increase in leukotriene B4 generation by peritoneal macrophages compared with unstimulated cells (P less than .001). The coincubation of peritoneal macrophages with gram-negative organisms (n = 3), however, did not result in an increase in leukotriene B4 synthesis. In contrast, all the organisms tested significantly inhibited the formation of prostaglandin E2 and thromboxane B2 but the degree of inhibition was species dependent. The above results were reproduced using bacteria-free supernatants, indicating that the interaction was dependent on a secreted bacterial product. Thus in response to certain bacterial species, the recruitment of neutrophils may be facilitated by the generation of leukotriene B4 from peritoneal macrophages. In addition, the reduction in synthesis of prostaglandin E2 may remove a regulatory effect that this metabolite has on the immune response.

Adult↗

Pathogenesis of peritoneal fibrosing syndromes (sclerosing peritonitis) in peritoneal dialysis.

Drawing from diverse sources including epidemiological and clinical data, surgical observations, histopathology, serosal healing responses to fibrin and fibrinolysis, tissue reaction to chronic exposure, and to exo- and endotoxins, new information on mesothelial stem cells, autocrine and paracrine influences on their proliferation and collagen synthesis, and the effect of glucose on fibroconnective tissue, we have begun to piece together the pathogenetic jigsaw of fibrosis in continuous ambulatory peritoneal dialysis (CAPD). The reaction of peritoneal mesothelium and stroma to the stress of continual dialysis results in a spectrum of alterations ranging from opacification through a tanned peritoneum syndrome to sclerosing encapsulating peritonitis (SEP). Any agent that causes irritation of the mesothelial layer and induces serositis, or single severe or multiple episodes of peritonitis resulting in mesothelial loss, predisposes the peritoneum to fibroneogenesis. An accurate definition of the histopathological changes of peritoneal thickening is a prerequisite for defining pathogenesis. This paper is the first attempt to create such a framework. It is evident from many areas of study that fibrin deposition and fibrinolysis, hyalinization of the superficial stromal collagen possibly tanned through nonenzymatic glycosylation by dialysate glucose and the proliferative potential of mesothelial stem cells play an important and possibly interdependent role in excessive fibroneogenesis in certain patients on CAPD. Many of the pieces of the jigsaw are obviously still missing, and the picture is most surely incomplete. Nevertheless, the outline of the pathologic and etiologic landscape should now be discernible.

Acetates↗

The influence of peritoneal catheter exit-site infections on peritonitis, tunnel infections, and catheter loss in patients on continuous ambulatory peritoneal dialysis.

The importance of exit-site infections (ESIs) as a source of peritonitis and catheter loss in continuous ambulatory peritoneal dialysis (CAPD) patients is unknown. We collected data on 137 CAPD patients over a 5-year period (2,052 cumulative patient months). Patients with a history of ESIs were more likely to have peritonitis and tunnel infections than patients without a history of ESIs. A larger percentage of patients with a history of ESIs lost catheters and transferred to hemodialysis than those without such a history, independent of the effect of peritonitis. These data confirm the importance of reducing the incidence of ESIs. More information is needed to determine the nature of the relationship between ESIs and peritonitis.

Adult↗

Peritonitis due to Curvularia inaequalis in an elderly patient undergoing peritoneal dialysis and a review of six cases of peritonitis associated with other Curvularia spp.

Fungal peritonitis due to Curvularia species in patients undergoing peritoneal dialysis is a very rare problem. We report a case of peritonitis caused by Curvularia inaequalis. This is the first report in the English literature of this species causing human infection. We also review the six previously reported cases of continuous ambulatory peritoneal dialysis peritonitis caused by other Curvularia species.

Aged↗

Suppressor resident peritoneal macrophages and peritonitis incidence in continuous ambulatory peritoneal dialysis.

Our study was designed to see if peritoneal macrophages (PM) of continuous ambulatory peritoneal dialysis (CAPD) uremic patients, by weakening local defense, could contribute to an increase of peritonitis incidence. Coincubation of nonadherent control responding cells (NACRC) and PM from normal subjects or CAPD patients with low peritonitis incidence (LPI) did not modify blastogenic response of cells to PHA. Coincubation of NACRC and PM from CAPD patients with high peritonitis incidence (HPI) produced noticeable decrease in blastogenic response; these PM, unable to produce normal amounts of Interleukin-1 (IL-1), released large amounts of prostaglandin E2 (PGE2). CAPD patients with LPI and normal subjects produced both substances in similar amounts. PM of CAPD patients with HPI were less able to kill bacteria than those from normal subjects and CAPD patients with LPI, showing a stronger suppressor effect on local defense. This suppressor activity correlated directly to PGE2 release and inversely to IL-1 production. We can hypothesize that in some uremic patients, subpopulations of macrophages growing in response to local stimuli produce humoral substances, negatively affecting cellular-mediated defense and favoring elevated bacterial expansion in peritoneum.

Adult↗

[Hyperthermic intra-peritoneal chemotherapy (HIPEC) in patients with peritoneal pseudomyxoma or peritoneal metastases of colorectal carcinoma; good preliminary results from the Netherlands Cancer Institute].

OBJECTIVE: To apply (HIPEC) using mitomycin in patients with peritoneal carcinomatosis. DESIGN: Descriptive. METHOD: The HIPEC treatment includes cytoreductive surgery and subsequent peritoneal lavage with exposure of the superficial tumour residues to a high concentration of a cytostatic drug at an intra-abdominal temperature of 40-42 degrees C. The HIPEC treatment was given to 24 patients with pseudomyxoma peritonei and to 29 patients with peritoneal carcinomatosis of colorectal origin. The adequate dose of mitomycin was determined in the Netherlands Cancer Institute in 26 patients: doses of 15 mg/m2 (n = 8), 25 mg/m2 (n = 3), 35 mg/m2 (n = 7) and 40 mg/m2 (n = 8) were administered. RESULTS: The maximal tolerable dose of mitomycin appeared to be 35 mg/m2, while unacceptable toxicity was recorded at a dose of 40 mg/m2. Therefore 35 mg/m2 was used in subsequent cases. Among the patients with pseudomyxoma peritonei 8 developed severe complications, two of which were fatal. After a median follow-up of 12 months, 21 patients were alive of whom 18 were free of disease. Among the patients with peritoneal carcinomatosis of colorectal origin one patient died from a treatment-related complication. After a median follow-up of 18 months, 18 patients were alive of whom 11 were free of disease. The actuarial 2 year survival was 59%. CONCLUSION: In the Netherlands Cancer Institute HIPEC treatment is considered the treatment of choice for pseudomyxoma peritonei. The results in cases of peritoneal carcinomatosis of colorectal origin are promising, but the results of a randomized trial are awaited.

Antibiotics, Antineoplastic↗

Peritoneal macrophages from patients on continuous ambulatory peritoneal dialysis have an increased capability to release tumour necrosis factor during peritonitis.

We have reported previously that human peritoneal macrophages collected from patients on Continuous Ambulatory Peritoneal Dialysis (CAPD) during an episode of peritonitis secrete increased amounts of interleukin-1 (IL-1), as compared to those collected during an infection free period, provided the cells were stimulated in vitro by LPS. We now report that such macrophages release also higher amounts of Tumor Necrosis Factor (TNF), if collected during peritonitis and stimulated subsequently in vitro by LPS. The increase in release of TNF was ascertained by radio-immunoassays as well as by bioassay of cytostatic effect against the highly sensitive TNF target-cell line L929 murine transformed fibroblasts. The present reported results, in addition to previously reported data on release of IL-1, indicate that induction of release of cytokines from human peritoneal macrophages is a dual stepwise process: first priming in vivo in an inflammatory environment and, secondly stimulation in vitro by LPS.

Adult↗

Antibacterial peritoneal defence in automated peritoneal dialysis: advantages of tidal over continuous cyclic peritoneal dialysis?

In tidal peritoneal dialysis (TPD) only a part of the infused dialysate is drained with each exchange, leaving a residual volume on top of which fresh fluid is cycled. As the persistent presence of a buffered intraperitoneal reserve volume might favour peritoneal macrophage (PMO) function, PMO obtained from eight patients during a 3-h continuous cyclic peritoneal dialysis (CCPD) or TPD session were studied in a randomized cross-over trial. PMO were studied for uptake of E. coli (complement-dependent) and S. epidermidis (antibody-dependent), as well as for their killing capacity and peak chemiluminescence response. In addition, dialysate was sampled during both treatment sessions and studied for pH, osmolality, and effect on the viability of donor phagocytes and mesothelial cells. TPD-derived PMO were significantly better able to phagocytose E. coli than CCPD-PMO (48 +/- 8 versus 33 +/- 6% uptake, P < 0.05), whereas the other tested functional capacities revealed no significant difference between TPD- and CCPD-PMO. During TPD dialysate pH ranged from 6 to 7 as compared to a pH range from 5 to 7 in CCPD. The presence of a residual dialysate volume resulted in less wash-out of cells and opsonins early in the treatment, and to some extent blunted the noxious effects of fresh dialysis solutions. Overall, however, tidal PD appeared to have no advantage over CCPD regarding preservation of peritoneal defences.

Adult↗

Neutral-pH peritoneal dialysis solution improves peritoneal function and decreases matrix metalloproteinase-2 (MMP-2) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

BACKGROUND: Conventional lactate-buffered peritoneal dialysis (PD) solutions have several bioincompatible characteristics, including acidic pH, lactate buffer, and the presence of glucose degradation products (GDPs), and these characteristics contribute to membrane dysfunction in PD patients. The formation of GDPs can be reduced by separating the glucose component of the solution from the lactate component during sterilization. This study was carried out to evaluate the clinical effect of dual-chambered neutral-pH PD solution in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: Thirteen CAPD patients using conventional PD solution were enrolled in this study. The fast peritoneal equilibration test (fast PET) was performed periodically before and after treatment with neutral PD solution. The concentration of matrix metalloproteinase-2 (MMP-2) in dialysate effluent was measured using 4-h dwelling 2.5% glucose dialysis solution. The patients were categorized into two groups, according to the value of the initial dialysate/plasma (D/P) creatinine ratio: i.e., lower transporters (group L, D/PCr < 0.65) and higher transporters (group H, D/PCr >/= 0.65). RESULTS: The mean D/P creatinine ratio measured by fast PET, was significantly decreased (0.72 +/- 0.09 to 0.60 +/- 0.06; P < 0.03) after treatment with neutral PD solution in group H. The mean glucose level in 4-h dwelling dialysate effluent was elevated (824.6 +/- 195.9 mg/dl to 942.6 +/- 147.8 mg/dl; P < 0.022) in all subjects. In group H, a significant decrease of MMP-2 in the dialysate effluent was recognized from 15 months after the beginning of treatment with the neutral PD solution (141.4 +/- 52.5 ng/ml to 91.3 +/- 15.1 ng/ml; P < 0.05), with the lowest value being shown at 21 months (80.0 +/- 31.8 ng/ml; P < 0.03). CONCLUSIONS: Neutral-pH peritoneal dialysis solution decreased the MMP-2 level in dialysate and improved peritoneal function in high-transporter patients with CAPD treatment.

Adult↗

Glucose degradation product methylglyoxal enhances the production of vascular endothelial growth factor in peritoneal cells: role in the functional and morphological alterations of peritoneal membranes in peritoneal dialysis.

Peritoneal membrane permeability deteriorates in peritoneal dialysis (PD) patients. We test whether glucose degradation products (GDPs) in PD fluids, glyoxal, methylglyoxal and 3-deoxyglucosone, stimulate the production of vascular endothelial growth factor (VEGF), a factor known to enhance vascular permeability and angiogenesis. VEGF increased in cultured rat mesothelial and human endothelial cells exposed to methylglyoxal, but not to glyoxal or 3-deoxyglucosone. VEGF also increased in peritoneal tissue of rats given intraperitoneally methylglyoxal. VEGF and carboxymethyllysine (CML) (formed from GDPs) co-localized immunohistochemically in mesothelial layer and vascular walls of the peritoneal membrane of patients given chronic PD. By contrast, in the peritoneum of non-uremic subjects, VEGF was identified only in vascular walls, in the absence of CML. VEGF production induced by GDPs may play a role in the progressive deterioration of the peritoneal membrane.

Animals↗

Increased peritoneal permeability in patients with peritonitis undergoing continuous ambulatory peritoneal dialysis.

The distribution of cefuroxime (250 mg) was studied in patients with renal failure undergoing continuous ambulatory peritoneal dialysis (CAPD). 10 uninfected patients received the drug intravenously and intraperitoneally, while 9 patients with peritonitis were randomly allocated to intravenous or intraperitoneal administration. Samples were taken over the first 6 hour dialysis period. In the infected patients, more drug (p less than 0.01) crossed into the peritoneal cavity following intravenous injection and reached the systemic circulation following intraperitoneal administration than in the uninfected group. This increased permeability of the peritoneal membrane during infection may result in unexpected systemic toxicity in patients treated with intraperitoneal antibiotics.

Adult↗