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Obesity is a risk factor for peritonitis in the Australian and New Zealand peritoneal dialysis patient populations.

OBJECTIVE: The aim of the present investigation was to examine the association between body mass index (BMI) and peritonitis rates among incident peritoneal dialysis (PD) patients in a large cohort with long-term follow-up. DESIGN: Retrospective observational cohort study of the Australian and New Zealand PD patient population. SETTING: Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. PARTICIPANTS: The study included all incident adult patients (n = 10 709) who received PD in Australia and New Zealand in the 12-year period between 1 April 1991 and 31 March 2003. Patients were classified as obese (BMI > or = 30 kg/m2), overweight (BMI 25.0 - 29.9 kg/m2), normal weight (20 - 24.9 kg/m2), or underweight (< 20 kg/m2). MAIN MEASUREMENTS: Time to first peritonitis and episodes of peritonitis per patient-year were recorded over the 12-year period. RESULTS: Higher BMI was associated with a shorter time to first peritonitis episode, independent of other risk factors [hazard ratio 1.08 for each 5-kg/m2 increase in BMI, 95% confidence interval (CI) 1.04 - 1.12, p < 0.001]. When peritonitis outcomes were analyzed as episodes of peritonitis per patient-year, these rates were significantly higher among patients with higher BMI: underweight 0.69 episodes/year (95% CI 0.66 - 0.73), normal weight 0.79 (95% CI 0.77 - 0.81), overweight 0.88 (95% CI 0.85 - 0.90), obese 1.06 (95% CI 1.02 - 1.09). Coronary artery disease and chronic lung disease were associated with both shorter time to first peritonitis and higher peritonitis rates, independently of these other factors. There was also a "vintage effect," with lower peritonitis rates seen among people who commenced dialysis in more recent years. CONCLUSIONS: Higher BMI at the commencement of renal replacement therapy is a significant risk factor for peritonitis. The mechanisms for this remain undefined.

Adolescent↗

EIPL (extensive intraoperative peritoneal lavage) therapy significantly reduces peritoneal recurrence after pancreatectomy in patients with pancreatic cancer.

One standing problem in the therapy for pancreatic cancer is peritoneal recurrence after pancreatectomy. We have established EIPL (extensive intra-operative peritoneal lavage) therapy as a very simple and non-aggressive prophylactic treatment for peritoneal dissemination of gastric cancer patients with peritoneal free cancer cells. In this study, the impact of EIPL therapy in preventing peritoneal recurrence in patients with pancreatic cancer after a curative surgical operation is analyzed. This study was based on 39 consecutive patients with invasive ductal adenocarcinoma of the pancreas who underwent curative surgical treatment. The patients were divided into two groups: the non-EIPL group, patients without EIPL therapy (from 1995 to 2000) (n=24); and the EIPL group, patients with EIPL therapy (from 2001 to 2003) (n=15). Clinicopathological findings, recurrence patterns and cancer-free survival were compared between the two groups. In addition, to identify free cancer cells during the operation, both carcinoembryonic antigen (CEA)- and cytokeratin 20 (CK20)-specific intraoperative real-time RT-PCR was performed immediately after laparotomy, lymph node dissection and removal of the pancreas in six patients with curative pancreatic cancer. Peritoneal, hepatic, lymphatic, local, and extra-abdominal recurrence rates in the EIPL and non-EIPL groups were 6.7, 40.0, 26.7, 13.3 and 13.3%, and 45.8, 50.0, 20.8, 29.2 and 20.8%, respectively. Among these recurrence patterns, the peritoneal recurrence rate of the EIPL group was significantly lower than that of the non-EIPL (P=0.013). Real-time RT-PCR analysis identified intra-peritoneal free cancer cells in 0, 33 and 67% of patients immediately after laparotomy, lymph node dissection and removal of the pancreatic cancer, respectively. After EIPL therapy, however, no cancer cell was detected in the peritoneal cavity. EIPL therapy was the independent negative risk factor for peritoneal recurrence (P=0.044), and the cancer-free 2-year survival of the EIPL group showed improvement compared with that of the non-EIPL group and was near statistical significance (P=0.097). EIPL therapy significantly prevented peritoneal recurrence after curative operation of pancreatic cancer, and it may contribute to reducing the mortality rate of this aggressive disease. Continued investigation of this promising treatment regimen is warranted.

Aged↗

Peritonitis in continuous ambulatory peritoneal dialysis (CAPD): a multi-centre randomized clinical trial comparing the Y connector disinfectant system to standard systems. Canadian CAPD Clinical Trials Group.

Sixty-one new continuous ambulatory peritoneal dialysis (CAPD) patients were allocated to a Y connector-disinfectant (Amuchina, Italy) and 63 to standard systems (Baxter Systems II & III) in a randomized clinical trial addressing peritonitis rates in 8 CAPD programs in 6 Canadian cities. In the Y connector-disinfectant group, 15 patients experienced 21 episodes of peritonitis in 452 15 patients experienced 21 episodes of peritonitis in 452 patient-months or 1 per 21.53 patient-months. In the standard systems group, 30 patients experienced 47 episodes of peritonitis in 467 patient-months or 1 per 9.93 patient-months (p = 0.009). The peritonitis risk reduction was 61% (95% confidence limits 27-79%). Exit-site infections occurred in 36% of each group. Prior to the development of exit-site infection, the monthly risk for peritonitis was 3.12% for the Y connector disinfectant system and 7.37% for the standard system. After an exit-site infection, these probabilities increased to 6.15% and 15.47%, respectively. Skin organisms were responsible for peritonitis in 8/21 (38%) in the Y connector-disinfectant group and 30/47 (64%) in the standard group. There were 75 days hospitalized for peritonitis in the Y connector-disinfectant group compared to 257 days for the standard group. The Y connector disinfectant system decreases the peritonitis rate through its effect on skin organisms. Exit-site injections are a major source of organisms responsible for peritonitis.

Bacterial Infections↗

[Changes in residual dextrose and amount of total protein loss in the effluent during the clinical course of continuous ambulatory peritoneal dialysis-related peritonitis].

Solute permeability of the peritoneum accelerates considerably in continuous ambulatory peritoneal dialysis (CAPD)-related peritonitis. Residual dextrose (RD) (g/bag) and the amount of total protein loss (LP) (g/bag) in the effluent of dialysate were measured during the clinical course of 21 cases of CAPD-related peritonitis as markers of deranged peritoneal permeability. The following were the results obtained: 1) In 15 cases of intraluminal infection (simple peritonitis by microorganism contamination through the lumen of a peritoneal catheter), RD decreased on day 1 (p < 0.001) and day 3 (p < 0.001) after the onset of peritonitis, and LP increased on day 1 (p < 0.001) and day 3 (p < 0.01), compared to the values of the non-infected phase. Both parameters were restored on day 7 and day 14 by adequate therapeutic maneuver. 2) In 6 cases of periluminal infection (peritonitis caused by an organic lesion of infection along the peritoneal catheter), RD and LP persisted even on day 7 (p < 0.01), and recovered 10 days after surgical removal of the peritoneal catheter with simultaneous catheter replacement. It is concluded that both RD and LP are valuable markers in the evaluation of the clinical course of CAPD-related peritonitis, and are useful in deciding on therapeutic intervention.

Aged↗

Antifungal prophylaxis for secondary fungal peritonitis in peritoneal dialysis patients.

Our objective was to evaluate antifungal prophylaxis for secondary fungal peritonitis in peritoneal dialysis patients. The study was designed to investigate antifungal prophylaxis for fungal peritonitis and to compare the incidence of fungal peritonitis without (January, 1991-July, 1993) and with (August, 1993-December, 1995) antifungal prophylaxis. In a tertiary-referral university hospital, 122 end-stage renal disease (ESRD) patients (77 male, 45 female) during period A (1/91-7/93) were observed for 1832 patient-months with no antifungal prophylaxis. One hundred and twelve ESRD patients (71 male, 41 female) during period B (8/93-12/95) were observed over 1705 patient-months with antifungal prophylaxis with fluconazole. Fluconazole 200 mg was given orally (po) as first dose at the onset of antibiotic therapy, then 100 mg po every other day, and was continued for one week after the antibiotic therapy. Forty-nine patients (28 male, 21 female; mean age 48.8 years) developed 105 episodes of peritonitis during period A. Forty-eight patients (36 male, 12 female; mean age 53.8 years) developed 95 episodes of peritonitis during period B. Fifteen episodes of fungal peritonitis occurred over 1832 patient-months during period A. while four episodes of fungal peritonitis were observed over 1705 patient-months during period B. Twelve episodes of secondary fungal peritonitis occurred during period A, while only two episodes occurred during period B. This incidence of secondary fungal peritonitis was significantly reduced with antifungal prophylaxis (p < 0.02). No side effect of fluconazole was observed. In conclusion, secondary fungal peritonitis was significantly decreased following fluconazole antifungal prophylaxis at our center.

Adult↗

Peritoneal taurolidine lavage in children with localised peritonitis due to appendicitis.

Despite aggressive surgical treatment, rational antibiotic therapy, and modern intensive care, generalised peritonitis remains a major threat in the paediatric age group. Several adjuvant strategies such as peritoneal saline lavage and peritoneal drainage have been utilised. Taurolidine, derived from the amino acid taurine, has bactericidic, antiendotoxic, and antiinflammatory properties. It has been introduced previously for intraoperative peritoneal lavage in treating peritonitis in adults. The aim of our study was to evaluate the effect of peritoneal taurolidine lavage on the clinical course and serological inflammation markers in children with perforated appendicitis and localised peritonitis. A series of 27 children presenting with appendicitis between January 1999 and July 2001 were included in the study after parental informed consent. All patients underwent open appendectomy. Taurolidine peritoneal lavage was applied in 15 randomly selected children (eight girls and seven boys; mean age 10 years and 10 months). Twelve children received saline peritoneal lavage and served as the control group (six girls and six boys; mean age 9 years and 7 months). Blood was taken preoperatively and on postoperative days 1, 3, 7, and 14. Full blood cell count, C-reactive protein, endotoxin, interleukin-1, interleukin-6, soluble interleukin-2 receptor, tumour necrosis factor alpha, and procalcitonin were investigated to evaluate the serological course of inflammation. Both groups initially presented with severe inflammation as evidenced clinically and serologically. The clinical postoperative course was uneventful in 13/15 patients in the treatment group and 10/12 patients in the control group. The remaining patients presented complications: intraperitoneal abscess or early postoperative bowel obstruction. With regard to the serological inflammatory parameters, no significant differences were found between the two groups except for the soluble interleukin-2-receptor on the 7th postoperative day. In conclusion, the expected reduction of endotoxin levels and inflammatory activity in the treatment group was not evident. A significant advantage of adjuvant peritoneal taurolidine lavage in the surgical therapy of children with localised peritonitis due to appendicitis could not be shown in our study.

Anti-Infective Agents↗

Comparison of blood and peritoneal neutrophil activity in rabbits with and without peritonitis.

The neutrophil (polymorphonuclear cell, or PMN) function is an essential component of the host defense against infection. However, infection itself may alter PMN activity. To investigate both the effects of infection on PMN activity and PMN activity on survival, we evaluated control and infected blood and peritoneal PMN phagocytosis, chemotaxis, and superoxide anion production in rabbits with and without peritonitis. Control blood and peritoneal PMNs were obtained from noninfected rabbits which were subjected to intraperitoneal infusion of sterile hypertonic saline. Infected blood and peritoneal PMNs were obtained from rabbits which had undergone appendiceal devascularization and ligation 18 hr earlier. Phagocytosis was similar in all groups except for a threefold increase in normal peritoneal PMNs. Chemotaxis was inhibited by infection in the blood and peritoneal PMNs. Normal peritoneal PMNs also had decreased chemotaxis. Superoxide anion production was comparable in the infected and control blood; however, both control and infected peritoneal PMNs had elevated superoxide anion production. Of the infected rabbits, four died in 5 days or less. Of the six that lived, two developed intraabdominal abscesses. Blood and peritoneal PMN activity was similar in all rabbits despite their outcome. We conclude that (1) blood and peritoneal PMNs have different basal activities and responses to infection; (2) the milieu of the peritoneal cavity appears to alter the PMNs present; and (3) PMN activity did not predict morbidity or mortality.

Animals↗

Aquaporin-1 in the peritoneal membrane: Implications for water transport across capillaries and peritoneal dialysis.

Peritoneal dialysis (PD) is an established mode of renal replacement therapy, based on the exchange of fluid and solutes between blood in peritoneal capillaries and a dialysate that has been introduced in the peritoneal cavity. The dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. Computer simulations predicted that the membrane contains ultrasmall pores (radius < 3 A) responsible for the transport of solute-free water across the capillary endothelium during crystalloid osmosis. The distribution of the water channel aquaporin-1 (AQP1), as well as its molecular structure ensuring an exquisite selectivity for water perfectly fit with the characteristics of the ultrasmall pore. Treatment with corticosteroids induces the expression of AQP1 in peritoneal capillaries and increases water permeability and ultrafiltration in rats, without affecting the osmotic gradient and the permeability for small solutes. Studies in knockout mice provided further evidence that osmotically-driven water transport across the peritoneal membrane is mediated by AQP1. AQP1 and endothelial NO synthase (eNOS) show a distinct regulation within the endothelium lining peritoneal capillaries. In acute peritonitis, the upregulation of eNOS and increased release of NO dissipate the osmotic gradient and result in ultrafiltration failure, despite the unchanged expression of AQP1. These data illustrate the potential of the peritoneal membrane to investigate the role and regulation of AQP1 in the endothelium. They also emphasize the critical role of AQP1 during peritoneal dialysis and suggest that manipulating AQP1 expression may be used to increase water permeability across the peritoneal membrane.

Animals↗

Peritoneal mesothelial cells produce cytokines in a murine model of peritonitis.

BACKGROUND: Many of the effector mechanisms that characterize peritonitis are generated by neutrophils and macrophages. However, it is now appreciated that peritoneal mesothelial cells can also produce mediators of inflammation when grown in culture. This study tested the hypothesis that peritoneal mesothelial cells produce inflammation-related cytokines in a murine model of peritonitis. METHODS: Fifty Wistar rats were randomized to either a control group or a peritonitis group. Groups of five animals were sacrificed at 4, 18, 24, 48, and 96 h after the induction of peritonitis, which was induced by the administration of 5 mg zymosan intra-peritoneally. Control animals received an equal volume of phosphate-buffered saline. Monolayers of peritoneal mesothelial cells were obtained using an imprint technique. The expression and production of TNFalpha, IL-1beta, IL-10, and ICAM-I were determined using semi-quantitative reverse transcription- polymerase chain reaction, immunocytochemistry, and Western blotting. RESULTS: The mesothelial cells significantly expressed TNFalpha, IL-1beta, IL-10, and ICAM-I in a time-dependent manner. We were able to demonstrate increased production for each of these cytokines, and this coincided with the initial shedding of mesothelial cells and their regeneration within 96 h. CONCLUSIONS: Peritoneal mesothelial cells play a role in peritonitis by producing inflammation- associated cytokines. This implies that they may be suitable targets for molecular interventions aimed at modulating the effects of peritonitis.

Analysis of Variance↗

Effect of increased dialysate volume on peritoneal surface area among peritoneal dialysis patients.

Large dialysate volumes are often required to increase solute clearance for peritoneal dialysis patients. The resulting increase in solute clearance might be attributable to an increased plasma-to-dialysate concentration gradient and/or to an increased effective peritoneal surface area. One of the factors affecting the latter is the peritoneal surface area in contact with dialysate (PSA-CD). The aim of this study was to estimate the change in PSA-CD after a 50% increase in the instilled dialysate volume for patients undergoing peritoneal dialysis. PSA-CD was estimated by using a method applying stereologic techniques to computed tomographic (CT) scans of the peritoneal space. The peritoneal cavity of 10 peritoneal dialysis patients was filled with a solution containing dialysate, half-isotonic saline solution, and contrast medium. Peritoneal function tests and CT scanning of the abdomen were performed twice for each patient (with an interval of 1 wk), after instillation of a 2- or 3-L solution. Scanning of thin helical CT sections was performed, and 36 random sections of the abdomen were obtained after reconstruction. A grid was superimposed on the sections. The surface area was estimated by using stereologic methods. After instillation of the 2-L solution, the volume of the peritoneal solution at the time of CT scanning was 2.32 +/- 0.05 L. The PSA-CD was 0.57 +/- 0.03 m(2), ranging from 0.41 to 0.76 m(2). The use of the 3-L solution increased the peritoneal volume by 46 +/- 2%. PSA-CD increased by 18 +/- 2.3% to 0.67 +/- 0.04 m(2) (range, 0.49 to 0.84 m(2); P < 0.01). Creatinine mass transfer increased from 112 +/- 10 mg to 142 +/- 11 mg (P < 0.0001). The slope of the change of the plasma-to-dialysate creatinine concentration gradient with time decreased from -2.26 +/- 0.23 x 10(-2) to -1.97 +/- 0.16 x 10(-2) (P = 0.01). K(BD-0) (permeability-surface area product or mass area transfer coefficient at time 0 of the dwell) increased from 10.6 +/- 0.7 to 13.6 +/- 1.2 ml/min (P < 0.02). These data demonstrate that increasing the instilled dialysate volume by 50% for peritoneal dialysis patients results in significant increases in the PSA-CD and K(BD).

Adult↗

Heterogeneity in peritoneal transport during continuous ambulatory peritoneal dialysis and its impact on ultrafiltration, loss of macromolecules and plasma level of proteins, lipids and lipoproteins.

We investigated the effect of heterogeneity in the peritoneal transport of plasma proteins on dialysis efficiency and plasma levels of proteins, lipids and lipoproteins in 32 patients undergoing long-term continuous ambulatory peritoneal dialysis (CAPD; 9 females and 23 males, 18-76 years old). Eleven patients were studied on several occasions (at 0-42 months) and the remainder at 6-60 months on CAPD (n = 49). We have divided our patients arbitrarily into two equal groups according to their protein concentration in the peritoneal effluent at the end of an 8-hour cycle. Patients with a high peritoneal protein concentration (> or = 2 g/l/1.73 m2) have lower ultrafiltration capacity, higher glucose absorption rate and increased loss of most plasma proteins [including albumin, immunoglobulins (Ig), complement components and high-density lipoproteins (HDL)] compared to patients with a low peritoneal protein concentration (< 2 g/l/1.73 m2). Consequently, plasma levels of albumin, IgM and HDL were lower in patients with a high peritoneal protein concentration. The latter had also increased levels of plasma triglycerides and very-low-density lipoproteins. The difference observed in peritoneal transport between the groups could be ascribed only in part to the duration of CAPD treatment, and hence to the number of peritonitis episodes but not to medications. Therefore, we suggest that inherent constitutional factors may be responsible for some of the observed heterogeneity in the peritoneal transport of these patients which is already evident at the start of CAPD treatment. Patients with high peritoneal transport are exposed to an augmented atherogenic plasma lipid profile in addition to a reduction in dialysis efficiency (ultrafiltration failure). These patients may become prone also to nutritional and immunological disturbances. Therefore, we suggest taking these effects into consideration before choosing the appropriate dialysis modality in patients with increased peritoneal transport for plasma proteins.

Adolescent↗

Increased activity of lysosomal enzymes in the peritoneal fluid of bacterial peritonitis.

OBJECTIVE: The activity of lysosomal enzymes is increased in the cerebrospinal fluid of bacterial meningitis, suggesting that inflammation may cause leakage of lysosomal enzymes into the extracellular fluid. Our objective was to study the activity of 3 lysosomal enzymes in cell-free peritoneal fluid of patients with peritoneal inflammation. METHODS: The beta-galactosidase, beta-glucuronidase, and alpha-mannosidase activity (nmol 4-methylumbelliferone/mL/h); the total, polymorphonuclear, and mononuclear cell number; and chemical parameters were determined in the peritoneal fluid of 26 patients with culture-positive acute bacterial peritonitis, 13 patients (under antibiotic treatment) with culture-negative bacterial peritonitis, 6 patients with acute mesenteric lymphadenitis, and 26 control subjects who were operated on for surgical conditions without peritoneal inflammation. RESULTS: The median beta-galactosidase activity in the culture-positive bacterial peritonitis, mesenteric lymphadenitis, and controls was 175 (range: 63--2210), 50 (range: 37--56), and 16 (range: 8--32), respectively. The beta-glucuronidase was 488 (range: 79--998), 53 (range: 27--98), and 15 (range: 3--22), respectively. The alpha-mannosidase was 801 (range: 100-3172), 78 (range: 33--157), and 41 (range: 16--63), respectively. The differences of the enzyme activities among the groups of the subjects studied were significant, with the exception of the alpha-mannosidase activity between mesenteric lymphadenitis and controls. There was no significant correlation between the enzyme activities and the cytologic or chemical parameters studied. CONCLUSIONS: The elevation of the lysosomal enzymes' activity in the peritoneal fluid of patients with bacterial peritonitis seems to be a reliable index of peritoneal infection. Of the enzymes studied, the beta-glucuronidase and beta-galactosidase activities provide the best means for diagnosing bacterial inflammation of the peritoneal cavity.

Adolescent↗

Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial.

Small-solute clearance targets for peritoneal dialysis (PD) have been based on the tacit assumption that peritoneal and renal clearances are equivalent and therefore additive. Although several studies have established that patient survival is directly correlated with renal clearances, there have been no randomized, controlled, interventional trials examining the effects of increases in peritoneal small-solute clearances on patient survival. A prospective, randomized, controlled, clinical trial was performed to study the effects of increased peritoneal small-solute clearances on clinical outcomes among patients with end-stage renal disease who were being treated with PD. A total of 965 subjects were randomly assigned to the intervention or control group (in a 1:1 ratio). Subjects in the control group continued to receive their preexisting PD prescriptions, which consisted of four daily exchanges with 2 L of standard PD solution. The subjects in the intervention group were treated with a modified prescription, to achieve a peritoneal creatinine clearance (pCrCl) of 60 L/wk per 1.73 m(2). The primary endpoint was death. The minimal follow-up period was 2 yr. The study groups were similar with respect to demographic characteristics, causes of renal disease, prevalence of coexisting conditions, residual renal function, peritoneal clearances before intervention, hematocrit values, and multiple indicators of nutritional status. In the control group, peritoneal creatinine clearance (pCrCl) and peritoneal urea clearance (Kt/V) values remained constant for the duration of the study. In the intervention group, pCrCl and peritoneal Kt/V values predictably increased and remained separated from the values for the control group for the entire duration of the study (P < 0.01). Patient survival was similar for the control and intervention groups in an intent-to-treat analysis, with a relative risk of death (intervention/control) of 1.00 [95% confidence interval (CI), 0.80 to 1.24]. Overall, the control group exhibited a 1-yr survival of 85.5% (CI, 82.2 to 88.7%) and a 2-yr survival of 68.3% (CI, 64.2 to 72.9%). Similarly, the intervention group exhibited a 1-yr survival of 83.9% (CI, 80.6 to 87.2%) and a 2-yr survival of 69.3% (CI, 65.1 to 73.6%). An as-treated analysis revealed similar results (overall relative risk = 0.93; CI, 0.71 to 1.22; P = 0.6121). Mortality rates for the two groups remained similar even after adjustment for factors known to be associated with survival for patients undergoing PD (e.g., age, diabetes mellitus, serum albumin levels, normalized protein equivalent of total nitrogen appearance, and anuria). This study provides evidence that increases in peritoneal small-solute clearances within the range studied have a neutral effect on patient survival, even when the groups are stratified according to a variety of factors (age, diabetes mellitus, serum albumin levels, normalized protein equivalent of total nitrogen appearance, and anuria) known to affect survival. No clear survival advantage was obtained with increases in peritoneal small-solute clearances within the range achieved in this study.

Analysis of Variance↗

Changes in peritoneal coagulation and fibrinolysis after discontinuation of chronic peritoneal dialysis.

OBJECTIVES: To study changes in peritoneal function after transfer from chronic peritoneal dialysis (CPD) to hemodialysis (HD), especially the effects on peritoneal coagulation, fibrinolytic markers, and mesothelium. DESIGN: Prospective observational study. SETTING: A tertiary-care university hospital. PATIENTS: Nine patients who transferred from CPD to HD were enrolled in the study after giving fully informed consent. METHODS: After transfer to HD, the peritoneal cavity was lavaged with low glucose PD solution once per day through PD catheters left in place. Thrombin-antithrombin III complex (TAT) was measured serially as a marker of peritoneal coagulation. As fibrinolytic markers, fibrinogen/fibrin degradation products (FDP) and plasmin-alpha2-antiplasmin complex (PIC) were assessed. Cancer antigen 125 (CA125) was measured as a marker of mesothelial cell mass. RESULTS: Levels of peritoneal TAT and FDP were much higher than plasma levels, indicating high local fibrin turnover. Transfer to HD induced a significant fall in mean peritoneal TAT, from 115.8 +/- 52.1 to 60.7 +/- 21.8 ng/mL, p < 0.05. Except for 1 patient with a 20-fold increase, mean peritoneal FDP decreased significantly, from 43.6 +/- 11.1 to 19.6 +/- 3.5 microg/mL, p < 0.05. Mean peritoneal PIC increased significantly, from 1.9 +/- 0.4 to 3.9 +/- 0.6 microg/mL, p < 0.05. Peritoneal CA125 increased from 156.4 +/- 57.3 to 1426.2 +/- 389.4 U/mL, p < 0.05. CONCLUSIONS: Peritoneal fibrin turnover was accelerated on CPD and stabilized after transfer to HD. Transfer to HD also induced mesothelial regeneration.

Adult↗

Association between an increased surface area of peritoneal microvessels and a high peritoneal solute transport rate.

OBJECTIVE: The peritoneal solute transport rate (PSTR) often increases, especially for small solutes, during long-term peritoneal dialysis (PD) treatment. Although the mechanism by which PSTR increases in PD patients is not known, it is likely that an increased PSTR reflects an increased surface area of the peritoneal capillary and post-capillary venules (microvessels), but this has not previously been investigated. The aim of this study was to clarify the relationship between PSTR and peritoneal microvessel alterations in biopsy specimens of peritoneum obtained from PD patients after various times on PD, and the possible contribution of the duration of PD in relation to these alterations. DESIGN: Tissue from the parietal peritoneum was obtained from 22 PD patients (age 48.5 +/- 9.0 years, duration of PD 66.3 +/- 46.6 months, incidence of peritonitis 0.3/patient-year). The patients were subdivided into three groups according to duration of PD: zero months (group 0, n = 4), less than 60 months (group I, n = 7), and more than 60 months (group II; n = 11). METHODS: For each specimen, the relative microvessel area (RVA) calculated as total area of microvessels/total area of peritoneal field, and the relative microvessel number (RVN), calculated as number of microvessels/total area of peritoneal field, were determined. The ratio RVA/RVN was used to assess the average area of microvessels. The PSTR was evaluated for creatinine, glucose, beta2-microglobulin, and albumin using the peritoneal equilibration test. RESULTS: The dialysate-to-plasma concentration ratio (D/P) for creatinine showed a significant positive correlation with both RVA (rho = 0.77, p < 0.001) and RVA/RVN (rho = 0.51, p = 0.01), but not with RVN. The D/P for beta2-microglobulin correlated with RVA (rho = 0.51, p = 0.015) but not with RVN or RVA/RVN. No differences were found between the three groups in the values for RVN, whereas there was an apparent significant increase in RVA with time on PD (p < 0.001 for group 0 vs both groups I and II). Furthermore, in high transporters, RVA tended to be higher in group II than in group I. CONCLUSIONS: The present study demonstrates for the first time that an increased peritoneal solute transport rate (for both creatinine and beta2-microglobulin) is associated with an increased surface area of peritoneal microvessels, especially in patients on long-term PD treatment. This indicates that increased vascularization and/or dilatation of peritoneal microvessels may play a key role in the development of a high PSTR.

Adult↗

Independent effects of renal and peritoneal clearances on the mortality of peritoneal dialysis patients.

OBJECTIVE: Previous studies show that peritoneal Kt/V is an independent predictor of survival in anuric patients receiving continuous ambulatory peritoneal dialysis (CAPD). We studied whether peritoneal Kt/V has the same effect in CAPD patients with residual renal function. DESIGN: Observational cohort study. SETTING: Single dialysis center in a university teaching hospital. PATIENTS: New and prevalent CAPD patients. METHODS: We examined the 5-year follow-up results of our prospective study previously reported (Kidney Int 2000; 58:400-7). A total of 270 CAPD patients were followed for up to 6 years. Dialysis adequacy indices, residual renal function, and nutritional data were monitored. OUTCOME MEASURES: Primary outcomes included mortality and technique failure. Peritoneal Kt/V rather than total Kt/V was used for multivariate survival analysis. RESULTS: Average duration of follow-up was 35.1 +/- 22.0 months. Average peritoneal Kt/V throughout the study was 1.59 +/- 0.37; median residual glomerular filtration rate (GFR) 0.82 mL/minute. Five-year actuarial patient survival was 41.5%, and technique survival was 23.1%. Multivariate analysis showed that sex, age, duration of dialysis, presence of diabetes, serum albumin, dialysate-to-plasma creatinine ratio at 24 hours, peritoneal Kt/V, residual GFR, and normalized protein nitrogen appearance were independent factors of both actuarial patient survival and technique survival. For every 0.1 unit higher peritoneal Kt/V, relative mortality risk was 0.94 (95% Cl 0.89 - 0.99, p = 0.03). When prevalent and new CAPD cases were analyzed separately, peritoneal Kt/V predicted survival only for prevalent CAPD patients. CONCLUSION: We conclude that, in prevalent CAPD patients with relatively low levels of peritoneal clearance and residual renal function, a higher peritoneal Kt/V is associated with better survival. Peritoneal clearance below 1.6-1.7 likely has a major detrimental effect on the clinical outcome of CAPD patients with little residual renal function.

Actuarial Analysis↗

Determinants of peritoneal solute transport rates in newly started nondiabetic peritoneal dialysis patients.

OBJECTIVE: An overrepresentation of a fast peritoneal transport status in new peritoneal dialysis (PD) patients with extensive comorbidity has been reported in some studies. High mass transfer area coefficients (MTACs) of low MW solutes suggest the presence of a large effective peritoneal surface area. The mechanism is unknown. It might include comorbidity, chronic inflammation, or an effect of mesothelial cell mass on peritoneal transport by the production of vasoactive substances. To investigate their relative importance in early PD, peritoneal permeability characteristics in incident PD patients were analyzed for relationships with comorbidity, serum concentrations of inflammatory markers, and products of the mesothelial cells that can be detected in dialysate. DESIGN: A cross-sectional study. SETTING: A university hospital. METHODS: 46 patients who fulfilled the following inclusion criteria were analyzed: a standard peritoneal permeability analysis (SPA) within 6 months after the start of PD, no peritonitis prior to the SPA, older than 18 years, and without diabetes mellitus as a primary renal disease. The patients were divided into tertiles based on the MTAC creatinine: slow, medium, and fast transport groups. The Davies comorbidity score was used to assess comorbidity. Serum and dialysate samples obtained during the SPA were used to determine hyaluronan, interleukin (IL)-6, vascular endothelial growth factor (VEGF), and cancer antigen 125 (CA125). The dialysate concentrations of these substances were expressed as their dialysate appearance rates. RESULTS: No significant differences were present in the three transport groups for comorbidity, serum concentrations of inflammatory markers, or serum VEGF. Interleukin-6 and VEGF concentration attributed to local VEGF production were not different between the tertiles. Levels of VEGF were higher in the medium transport group compared to the slow transport group (p = 0.02); CA125 was higher in the fast transport group compared to the medium transport group (p= 0.01). When analyzed as continuous variables, MTAC creatinine was related to VEGF (r= 0.33, p < 0.05) and CA125 (r= 0.41, p = 0.03). In linear regression analysis, VEGF influenced the association between CA125 and MTAC creatinine; IL-6 weakened this association only marginally. CONCLUSION: A fast peritoneal transport status in incident nondiabetic PD patients was not related to comorbidity. The relationships found between VEGF, CA125, and MTAC creatinine may suggest a role of VEGF in the regulation of the vascular peritoneal surface area, possibly already before structural abnormalities have developed. Our analyses are consistent with the hypothesis that mesothelial cell mass is an important determinant of the peritoneal transport status in incident nondiabetic PD patients without previous peritonitis. Of the many potential mediators produced by mesothelial cells, VEGF was more important than the inflammation marker IL-6.

Biological Transport↗

The relationship between peritoneal transport characteristics and messenger RNA expression of aquaporin in the peritoneal dialysis effluent of CAPD patients.

BACKGROUND: Cell culture experiments show that peritoneal mesothelial cells express aquaporin-1 (AQP1) and aquaporin-3 (AQP3), which can be important for peritoneal transport. However, the functional relevance of aquaporin in mesothelial cells remains uncertain because endothelial cells are generally regarded as the major barrier of peritoneal transport. METHODS: We studied 74 prevalent peritoneal dialysis (PD) patients. Peritoneal permeability was determined by the standard peritoneal equilibration test (PET). Messenger RNA (mRNA) was extracted from the peritoneal dialysis effluent (PDE) after PET, and the aquaporin gene expression was determined by quantitative polymerase chain reaction (PCR). RESULTS: AQP3 mRNA expression in PDE correlated closely with peritoneal transport characteristics, including dialysate-to-plasma creatinine (Cr) ratio at 4 hr (D/P4) (r=0.42, p=0.007), mass transfer area coefficient (MTAC) of Cr (r=0.60, p<0.0001), and net ultrafiltration (UF) (r=0.34, p=0.03). On the other hand, AQP1 mRNA expression did not correlate with D/P4 (r=0.21, p=0.2), MTAC of Cr (r=0.05, p=0.7), or with net UF (r=0.17, p=0.3). There was a modest correlation between AQP3 and connective tissue growth factor (CTGF) mRNA expression in PDE (r=0.30, p=0.06), while AQP1 expression correlated closely with CTGF expression (r=0.56, p=0.0002) and vascular endothelial growth factor (VEGF) expression (r=0.37, p=0.02). AQP3 expression was unaffected by dialysis duration or peritonitis history. The expression of neither AQP1 nor AQP3 correlated with that of transforming growth factor. CONCLUSIONS: Since mesothelial cells are the major source of aquaporin mRNA found in PDE, our findings support a functional role for mesothelial AQP3 in peritoneal transport. Our findings also suggest that AQP3 expression in vivo is regulated by mechanisms other than glucose exposure, peritonitis and traditional growth factors.

Adult↗