Peritoneal dialysis effluent as a non-potable water resource: Biochemical and microbiological characterization compared to treated wastewater.

IgG, C3 and transferrin in peritoneal dialysis effluent of patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were 1%-2% of those in serum. In contrast, the values in normal peritoneal fluid were not significantly different from those in serum. The three proteins correlated with each other in peritoneal dialysis effluent, but were independent of the amount in the corresponding patients' sera. There was also an overall inverse correlation between total protein in peritoneal dialysis effluent and time on CAPD during the first 6 months of treatment but not thereafter, which suggests that changes in membrane permeability occur during the early months. In peritoneal dialysis effluent, but not in normal peritoneal fluid, there was a correlation between opsonising capacity and IgG or C3 concentrations. An inverse correlation between opsonic activity of peritoneal dialysis effluent and frequency of peritonitis was also found. Peritoneal dialysis effluent permitted significantly faster multiplication of Staphylococcus epidermidis than sera or normal peritoneal fluid, and the growth rate correlated inversely with the transferrin levels in peritoneal dialysis effluent. Overall IgG, C3 and transferrin in peritoneal dialysis effluent are inadequate for optimal opsonising and bacteriostatic activity, and the peritoneal cavities of CAPD patients are therefore immunocompromised sites.

Increased production of hyaluronan by peritoneal cells and its significance in patients on CAPD.

Dialysate cell population and cancer antigen 125 in stable continuous ambulatory peritoneal dialysis patients: Their relationship with transport parameters

Opsonic deficiency of peritoneal dialysis effluent in continuous ambulatory peritoneal dialysis

To evaluate peritoneal immunological defenses and to find a way to prevent peritonitis we have studied the capacity of peritoneal dialysis effluent (PDE) to opsonize bacteria, and the phagocytic activity of peritoneal macrophages (PM). The subjects were 40 uremic patients followed for a mean period of 36 months and 40 normal women who underwent laparoscopy (controls). Opsonic capacity for Staphylococcus epidermidis of undiluted PDE from CAPD patients with low peritonitis incidence (LPI) proved to be similar to that of 10% control serum. However, the capacity of effluent from patients with a high peritonitis incidence (HPI) was noticeably inferior. In these cases, IgG concentration in PDE was lower than in LPI patients. There was a significant correlation between opsonization capacity for bacteria and IgG concentration values in PDE. We found inverse correlations between opsonic capacity of PDE and number of episodes of peritonitis. Phagocytic capacity of PM from CAPD patients was similar to that of control PM when micro-organisms were preopsonized by control serum. Treatment with intraperitoneal intmunoglobulin raised PDE opsonization capacity and lowered the incidence in those with previous HPI, thus demonstrating the importance of abnormal opsonization in CAPD peritonitis and the possibility of preventing infection by prophylaxis with intraperitoneal immunoglobulin. Intravenous immunoglobulin does not reduce the incidence of infection.

Peritoneal dialysis (PD) is frequently complicated by high rates of peritonitis, which result in hospitalization, technique failure, transfer to hemodialysis, and increased mortality. Early diagnosis, and identification of contributing factors are essential components to increasing effectiveness of care. In previous reports, neutrophil gelatinase-associated lipocalin (NGAL), a lipocalin which is a key player in innate immunity and rapidly detectable in peritoneal dialysis effluent (PDE), has been demonstrated to be a useful tool in the early diagnosis of peritonitis. This study investigates predictive value of PDE NGAL concentration as a prognostic indicator for PD-related peritonitis. A case-control study with 182 PD patients was conducted. Plasma and PDE were analyzed for the following biomarkers: C-reactive protein (CRP), blood procalcitonin (PCT), leucocytes and NGAL in PDE. The cases consisted of patients with suspected peritonitis, while controls were the patients who came to our ambulatory clinic for routine visits without any sign of peritonitis. The episodes of peritonitis were defined in agreement with International Society for Peritoneal Dialysis guidelines. Continuous variables were presented as the median values and interquartile range (IQR). Mann-Whitney U test was used to compare continuous variables. Univariate and multivariate logistic regression were used to evaluate the association of biomarkers with peritonitis. Receiver operating characteristic (ROC) curve analysis was used to calculate area under curve (AUC) for biomarkers. Finally we evaluated sensitivity, and specificity for each biomarker. All statistical analyses were performed with SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). During the 19-month study, of the 182 patients, 80 had a clinical diagnosis of peritonitis. C-reactive protein levels (p < 0.001), PCT (p < 0.001), NGAL in PDE (p < 0.001), and white blood cells (WBC) in PDE (p < 0.001) were all significantly different in patients with and without peritonitis. In univariate analysis, CRP (odds ratio [OR] 1,339; p = 0.001), PCT (OR 2,473; p < 0,001), WBC in PDE (OR 3,986; p < 0,001), and NGAL in PDE (OR 36.75 p < 0.001) were significantly associated with episodes of peritonitis. In multivariate regression analysis, only WBC (OR 24.84; p = 0,012), and peritoneal NGAL levels (OR 136.6; p = 0,01) were independent predictors of peritonitis events. Moreover, AUC for NGAL in peritoneal effluent was 0,936 (p < 0.001) while AUC for CRP, PCT, and WBC count in peritoneal effluent were 0,704 (p = 0.001), 0.762 (p = 0.039), 0,975 (p < 0.001), respectively. Finally, combined WBC and peritoneal NGAL test increased the specificity (= 96%) of the single test. These results identify NGAL in peritoneal effluent as a reliable marker of peritonitis episodes in PD patients. Collectively, our findings demonstrate that the use of peritoneal NGAL cooperatively with current clinical diagnostic tools as a prognostic indicator, presents a valuable diagnostic tool in PD-associated peritonitis.

Genetic polymorphism of VEGF: Impact on longitudinal change of peritoneal transport and survival of peritoneal dialysis patients

The peritoneal immune compartment is a microenvironment with a particular T-cell repertoire and susceptible to local inflammation. To clarify the role of T lymphocytes in peritoneal immunity, the changes in T-cell subpopulations in peritoneal dialysis effluents (PDEs), and their influence on the response to the treatment of peritonitis and on its prognosis were studied in patients undergoing long-term, continuous ambulatory peritoneal dialysis (CAPD). A cohort of 36 patients treated with CAPD and who had histories of peritonitis were divided into a group with rapid and a group with delayed response to antibiotics, and were followed for 3 years. CD4/CD8 T-cell ratios, T-cell cytokine mRNA expression patterns and transforming growth factor-beta1 (TGF-beta1) concentrations were examined in PDE during bouts of peritonitis. The change in 4 h D/P creatinine during the peritoneal equilibration test (PET) between year 0 and year 3 was expressed as deltaD/P creatinine. The serial changes in T-cell subsets in PDE during peritonitis showed two patterns: (i) pattern 1, manifest as a progressive increase in the CD4/CD8 ratio, and associated with a rapid response to treatment; and (ii) pattern 2, manifest as a progressive decrease in the CD4/CD8 ratio, and associated with a delayed response to treatment. The major T-cell phenotypes in PDE during peritonitis were Th1-CD4(+) and Tc2-CD8(+), determined by cloning techniques, RT-PCR and double immunofluorescence staining. TGF-beta1 in the effluent was undetectable in pattern 1 after 7-8 days, but remained detectable at 2 weeks in pattern 2. Pattern 2 patients had a significantly greater decrease (deltaD/P creatinine: -0.198+/-0.086) in solute transport than pattern 1 patients (deltaD/P creatinine: -0.036+/-0.077, P<0.05). These results suggest that a progressive decrease of the CD4/CD8 ratio in PDE correlates with a persistent expression of TGF-beta1, and plays a pathogenetic role in the evolution of peritonitis, PET deterioration and peritoneal fibrosis. Therefore, patterns of CD4/CD8 T-cell ratio in PDE may predict clinical outcomes of peritonitis in CAPD patients.

To evaluate the oxidative metabolism of polymorphonuclear leukocytes (PMNL) in continuous ambulatory peritoneal dialysis (CAPD) patients compared with those of hemodialysis (HD) patients, chronic renal failure (CRF) patients not yet on dialysis, and healthy controls; and to discover factors contributing to the oxidative function in CAPD patients. Thirty-five CAPD, 22 HD, 11 CRF patients were assessed; all were free from infections at the time of examination. Thirty-one healthy volunteers served as controls. The oxidative metabolism was estimated by the production of superoxide anion, which was detected by luminol-dependent zymosan stimulated chemiluminescence (CL) with whole blood assessment. The volume of superoxide production equivalent to 1 mL of circulating blood (T-CL), that equivalent to 10(4) neutrophils (CL/N) and the velocity of superoxide production (V-CL), were measured as parameters for the oxidative function of PMNL. There were no differences in all CL parameters between CAPD and HD patients. T-CL and CL/N of dialysis patients were equal to controls but those of CRF patients were significantly decreased. V-CL of dialysis patients, as well as CRF patients, was smaller than that of controls but the difference was not significant. Among nutritional status, degree of anemia, dialytic efficacy and duration of dialysis in CAPD patients, only serum albumin concentration (Alb) correlated well to all CL parameters. Hypoalbuminemic patients (Alb < 3.6 g/dL, n = 20) had significantly decreased T-CL and CL/N compared to normoalbuminemic patients (Alb > or = 3.6 g/dL, n = 15), and decreased CL/N and V-CL compared to controls. No differences in CL parameters were observed between the patients with a history of peritonitis (n = 15) and without a history of peritonitis (n = 20). Oxidative metabolism of PMNL in CAPD patients was maintained with respect to superoxide productive volume, while the oxidative velocity was relatively impaired. Furthermore, it seems that albumin has a great influence on the oxidative metabolism of PMNL in CAPD patients.

Nitric oxide plays an important role in mediating the inflammatory process. The aim of this study was to evaluate if nitric oxide production was increased during peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD), and the association with the prognosis. The study population comprised 21 patients with 22 episodes of peritonitis. Fifteen patients without peritonitis were controls. Nitrate was measured by HPLC and nitrite by the Griess method, to reflect nitric oxide production. Peritoneal dialysate effluent and plasma were collected from six patients during peritonitis and 1 week after treatment to study changes in dialysate:plasma ratio. In 15 patients, nitrite was measured during peritonitis and every 3 days for 2 weeks or until normalized for evolutional changes. The dialysate plasma ratios of nitrate and nitrite during peritonitis were reduced 26% and 41.5%, respectively, after 1 week of treatment, indicating the peritoneal production of nitric oxide during peritonitis. In the evolutional study, a 5.1-fold increase of peak nitrite levels in bacterial peritonitis (n=13) and a 2.5-fold increase in fungal peritonitis (n=3) were observed compared to controls. Nitrite gradually declined to control levels (9.3±7.2 days) after effective antibiotic treatment, but took longer than to normalize leukocyte count in the peritoneal dialysate effluent (3.9±1.9 days). In four patients with refractory peritonitis (Candida infection in three, Acinetobacter infection in one), the nitrite levels remained elevated 2-fold despite treatment, and the catheters were removed. It is concluded that nitrite levels in peritoneal dialysate effluent may serve as a marker to assess treatment efficacy in CAPD patients with peritonitis.

Nitric oxide plays an important role in mediating the inflammatory process. The aim of this study was to evaluate if nitric oxide production was increased during peritonitis in patients receiving continuous ambulatory peritoneal dialysis (CAPD), and the association with the prognosis. The study population comprised 21 patients with 22 episodes of peritonitis. Fifteen patients without peritonitis were controls. Nitrate was measured by HPLC and nitrite by the Griess method, to reflect nitric oxide production. Peritoneal dialysate effluent and plasma were collected from six patients during peritonitis and 1 week after treatment to study changes in dialysate:plasma ratio. In 15 patients, nitrite was measured during peritonitis and every 3 days for 2 weeks or until normalized for evolutional changes. The dialysate:plasma ratios of nitrate and nitrite during peritonitis were reduced 26% and 41.5%, respectively, after 1 week of treatment, indicating the peritoneal production of nitric oxide during peritonitis. In the evolutional study, a 5.1-fold increase of peak nitrite levels in bacterial peritonitis (n = 13) and a 2.5-fold increase in fungal peritonitis (n = 3) were observed compared to controls. Nitrite gradually declined to control levels (9.3 +/- 7.2 days) after effective antibiotic treatment, but took longer than to normalize leukocyte count in the peritoneal dialysate effluent (3.9 +/- 1.9 days). In four patients with refractory peritonitis (Candida infection in three, Acinetobacter infection in one), the nitrite levels remained elevated 2-fold despite treatment, and the catheters were removed. It is concluded that nitrite levels in peritoneal dialysate effluent may serve as a marker to assess treatment efficacy in CAPD patients with peritonitis.

HIV drug resistance mutations (HIVDRMs) are important determinants of therapeutic effects and outcomes even in end-stage kidney failure (ESKF) people living with HIV (PLWHIV). This study evaluated the prevalence of HIVDRMs and their effect on the shedding of HIV-1 into peritoneal dialysis (PD) effluents. This cross-sectional study of PLWHIV and having ESKF and managed with antiretroviral therapy (ART) and PD,collected enrolled patients' demographic information, clinical and laboratory data, and sequenced HIV-1 RNA in unsuppressed plasma and PD effluent samples. HIV viral load and HIVDRMs were determined using qualitative polymerase chain reaction (qPCR) and Stanford University HIVDRM Database, respectively. There were 60 participants recruited with a median age of 43.0 (interquartilerange [IQR], 38.0-47) years and were predominantly on abacavir (88.3%), lamivudine (98.3%), and efavirenz (70%) for a median duration of 8 (IQR, 5-11) years. Among participants with detectable HIV-1 in PD effluents, the prevalence of HIVDRMs was 62.5% (5/8) compared to 7.7% (4/52) among those with undetectable HIV-1 (p = 0.001) with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations predominating. On Spearman's correlation analysis, high plasma HIV levels(ρ = 0.649, p < 0.001), T-cell CD4 count (ρ = -0370, p < 0.004), serum creatinine (ρ = -0.396, p < 0.002), and white blood cell count (ρ = -0.294, p < 0.023) levels were significant factors correlated with the detection of HIV-1 in PD effluents. Moreover, HIVDRMs presence (ρ = 0.504, p < 0.001) particularly NNRTI resistance (ρ = 0.504, p < 0.001)were also significantly correlated with detection of HIV-1 in PD effluents. The presence of HIVDRMs, high plasma HIV viral load, and T-cell CD4 count were correlated with HIV-1 shedding into PD effluents.

We studied the peritoneal transport properties in 175 stable continuous ambulatory peritoneal dialysis (CAPD) patients seeking a simple and handy assessment of peritoneal permeability to small solutes. Measurement of creatinine in biological fluid was known to suffer from interference by high glucose concentration in the sample. Furthermore, the interference is also affected by the creatinine concentration of the specimen. Peritoneal transport properties were studied by determining the dialysate to plasma ratio of creatinine concentration (D/P) at the fourth hour of the peritoneal equilibration test, and the mass transfer area coefficient of creatinine (MTACCr) or glucose (MTACGlu). The ratio of glucose concentration in peritoneal dialysate effluent (PDE) at 4 and 0 h (G4/G0) was examined and compared with various peritoneal parameters. There were significant logarithmic correlations between D/P or G4/G0 with MTACCr (r = 0.96 and 0.79, respectively, p < 0.0001). The correlation between G4/G0 and D/P was linear (r = –0.82, p < 0.0001). A fairly good agreement was present between G4/G0 and D/P by Bland and Altman’s method. The bias was –0.93% with 95% confidence interval –23.29% to 21.43% of the measured value. Systematic error was found when D/P or G4/G0 were compared with MTACCr. D/P under estimated MTACCr in the high range. The reverse happened for G4/G0. Net ultrafiltration (NUF) also correlated with MTACCr, D/P and G4/G0 (r = –0.32, p < 0.001; –0.26, p < 0.01; and 0.16, p < 0.05, respectively.In conclusion, the use of G4/G0 as a measure of peritoneal transport in CAPD is an acceptable alternative to D/P. It is highly reproducible and avoids correction of interference when creatinine transport parameters are measured. Because of the logarithmic relations of G4/G0 (or D/P) with MTACCr, the former should not be directly converted to MTACCr. Such a simple measure of peritoneal permeability is, however, most convenient for serial monitoring and can be useful to detect early loss of ultrafiltration or solute clearance.

This study aimed to clarify the role of peritoneal T-lymphocytes in peritoneal immune defense mechanisms. This study was designed to examine the changes in T-cell subpopulations during peritonitis in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Our observations were correlated to responses to treatment and with outcomes. The present study was carried out in 20 patients (8 males, 12 females) under CAPD. Peritonitis was diagnosed according to the criteria defined by the Ad Hoc Advisory Committee on Peritonitis Management. Peritoneal dialysate effluent (PDE) samples were collected from our patients, and lymphocyte subsets (CD2+, CD3+, CD3+/4+, CD3+/8+, CD3-/16+56+, CD4/CD8 ratio) were quantitated by using monoclonal antibodies. CD4/CD8 ratio was measured every day during peritonitis until the patients had completely recovered. The serial measurements of the CD4/CD8 ratio made in the PDE during peritonitis followed two patterns: the first pattern was characterized by a progressive increase in the CD4/CD8 ratio. The CD4/CD8 ratios on days 5, 6, and 7 were significantly higher than those on day 1 (P < 0.05). Overall, the patients who exhibited pattern 1 had favorable clinical courses. The second pattern was characterized by high initial CD4/CD8 ratios, which progressively decreased significantly (P < 0.05). This second pattern was associated with a delayed clinical response to treatment. Symptoms and signs of peritonitis persisted beyond 72 h. The pattern of the CD4/CD8 ratio in PDE may determine the outcome of peritonitis in CAPD patients.

BACKGROUND AND AIMS The accumulating evidence presented thus far supports the idea that indoxyl sulfate (IS) is a trigger of chronic inflammation in end-stage kidney disease patients. However, although serum IS is one of the most extensively studied uremic toxins, no single study exists which has investigated the association between serum IS and intraperitoneal inflammation in peritoneal dialysis (PD) patients. The present study was undertaken to evaluate the association between serum total IS (tIS) concentration and the pro-inflammatory markers in peritoneal dialysis effluent (PDE) and peritonitis episodes in PD patients. METHOD In this observational cross-sectional study, we analysed serum tIS concentration and 24-h PDE levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein -1 (MCP-1) in 74 PD patients with an average age of 55 (38–64) years and dialysis vintage of 36 (30–58) months. All patients had been undergoing continuous ambulatory PD and had no PD-associated infectious complications for more than 3 months. Serum concentrations of tIS were determined using the spectrophotometry method. The concentrations of IL-6, TNF-α and MCP-1 in PDE were analysed using ELISA. For the statistical analysis, we stratified this PD patient cohort into two groups depending on experienced peritonitis: the peritonitis group (n = 48) and the peritonitis-free group (n = 26). The data were presented as the median and the interquartile ranges [Me (Q25–Q75)] and compared using the Kruskal–Wallis test. The Spearmen correlation test was performed to assess the association between IS and the pro-inflammatory markers. RESULTS Significant differences were found in serum concentrations of tIS and PDE levels of IL-6 between the peritonitis and the peritonitis-free PD patients (Table 1). In addition, serum tIS was significantly associated with number of experienced peritonitis episodes (r = 0.26, P = 0.022). Although PDE levels of TNF-a and MCP-1 did not differ between the peritonitis and the peritonitis-free groups in our cohort, they had a direct association with serum tIS similar to those of IL-6 (Fig. 1, 2). Moreover, serum tIS was statistically higher in the anuric PD patients compared with the non-anuric patients [33.6 (13.9–74) versus 20.2 (9.3–46) μg/mL, P = 0.043], had a negative association with residual renal function (r = −0.39, P = 0.0017) and, accordingly, total weekly Kt/V (r = −0.27, P = 0.026). CONCLUSION Serum tIS concentration has a significant direct association with PDE levels of the pro-inflammatory markers, high peritonitis episodes and their outcomes in PD patients. Further well-designed studies are required to establish the effect of serum tIS concentration on intraperitoneal inflammation and clinical outcomes in PD patients.