Changes In Peritoneal Transport Research Articles

Non-invasive assessment of peritoneal membrane alterations

The peritoneal dialysis membrane is subject to remodelling in the course of peritoneal dialysis. In the absence of longitudinal morphological studies, this process is mainly studied indirectly by the investigation of changes in peritoneal transport. Non-invasive assessment of the peritoneum is also possible by assessment of substances that originate from peritoneal tissues and can be determined either as their gene expression in peritoneal effluent cells and/or as proteins in peritoneal effluent. Three of these biomarkers will be discussed, because longitudinal data are available.
 Cancer antigen 125 (CA 125) is present on the mesothelium,while its gene (MUC 16) is expressed in peritoneal effluent cells and is related to dialysate CA 125 protein. The constitutive production and the small intra-individual variability of 15% indicate its usefulness as a follow-up marker of mesothelial cell mass. Dialysate appearance rate is higher on biocompatible than on conventional solutions, but both decrease during long-term follow-up.
 Interleukin-6 (Il-6) is present in peritoneal effluent due to both transport from the circulation and local intraperitoneal production. Its appearance rate is unrelated to its gene expression in peritoneal cells. The intra-individual variation of effluent Il-6 averages 28%, hampering the interpretation of cross-sectional values. The relationships between effluent Il-6 and peritoneal transport have been interpreted as microinflammation, but are difficult to interprete due to mathematical coupling.
 Plasminogen activator inhibitor-1 (PAI-1) is encoded by the SERPINE 1 gene. A relationship is present between effluent concentration and gene expression. PAI-1 production is stimulated by glucose. PAI-1 appearance rate increases with PD duration. The sensitivity of effluent PAI-1 for the diagnosis of encapsulating peritoneal sclerosis was 100% one year prior to the diagnosis and the specificity 56%.
 It can be concluded that the discussed biomarkers are useful extensions to transport in assessment of the peritoneum during dialysis.

Longitudinal Changes of NF-\u03baB Downstream Mediators and Peritoneal Transport Characteristics in Incident Peritoneal Dialysis Patients

The role of intra-peritoneal mediators in the regulation peritoneal transport is not completely understood. We investigate the relation between longitudinal changes in dialysis effluent level of nuclear factor kappa-B (NF-κB) downstream mediators and the change in peritoneal transport over 1 year. We studied 46 incident PD patients. Their peritoneal transport characteristics were determined after starting PD and then one year later. Concomitant dialysis effluent levels of interleukin-6 (IL-6), cyclo-oxygenase-2 (COX-2) and hepatocyte growth factor (HGF) are determined. There were significant correlations between baseline and one-year dialysis effluent IL-6 and COX-2 levels with the corresponding dialysate-to-plasma creatinine level at 4 hours (D/P4) and mass transfer area coefficient of creatinine (MTAC). After one year, patients who had peritonitis had higher dialysis effluent IL-6 (26.6 ± 17.4 vs 15.1 ± 12.3 pg/ml, p = 0.037) and COX-2 levels (4.97 ± 6.25 vs 1.60 ± 1.53 ng/ml, p = 0.007) than those without peritonitis, and the number of peritonitis episode significantly correlated with the IL-6 and COX-2 levels after one year. In contrast, dialysis effluent HGF level did not correlate with peritoneal transport. There was no difference in any mediator level between patients receiving conventional and low glucose degradation product solutions. Dialysis effluent IL-6 and COX-2 levels correlate with the concomitant D/P4 and MTAC of creatinine. IL-6 and COX-2 may contribute to the short-term regulation of peritoneal transport.

Trend of peritoneal transport and impact on patient survival: A 10-year follow-up cohort study .

Peritoneal transport has an impact on clinical outcomes, but it is not constant in peritoneal dialysis (PD) patients. Large-scale, longitudinal data in different types of transport patients are lacking. This study aimed to elucidate the changing trend of peritoneal transport and its impact on patient outcomes. All patients who entered the PD program in a local hospital in Hong Kong from 1995 to 2012 and underwent more than one peritoneal equilibration test (PET) were analyzed retrospectively, excluding those with peritonitis before the first PET. PET was performed yearly on a routine basis. Peritoneal transport was classified according to the dialysate-to-plasma creatinine ratio (D/P Cr). Survival rates of this cohort were analyzed for up to 10 years. A total of 470 patients fulfilled the study criteria, with a mean age of 63.2 ± 14.3 years and a 40% diabetes occurrence. Mean D/P Cr dropped significantly in the first year and remained constant thereafter. A slow, increasing trend was observed after year 5. In the first few years, D/P Cr declined significantly in the high and high-average transport patients and increased in the low-average and low transport patients. There was no significant difference in patient and technique survival rates according to baseline transport groups. D/P Cr only became a significant risk factor for mortality by year 3 onwards. A centripetal trend of change in peritoneal transport was observed in the first year. High peritoneal transport was associated with poorer patient outcomes only after the first few years of PD. The initial peritoneal transport status was not a determinant factor of patient survival in long-term PD. .

Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis.

Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.

The relationship between bone morphogenic protein-7 and peritoneal transport characteristics

After prolonged peritoneal dialysis (PD) and exposure to a non-physiological dialysis solution, peritoneal mesothelial cells undergo the epithelial-to-mesenchymal transition. In other biological systems, bone morphogenic protein-7 (BMP-7) is a key factor that controls this process. However, the role of BMP-7 in peritoneal physiology has not been studied. We studied the peritoneal transport characteristics of 50 consecutive new PD patients at 4 and 52 weeks after PD. Peritoneal permeability will be determined by the standard peritoneal equilibration test (PET). BMP-7 in PD effluent (PDE) at mRNA and protein level at 4 weeks was quantified. At 4 weeks, the mRNA expression of BMP-7 in PDE significantly correlated with peritoneal transport characteristics, including the dialysate-to-plasma creatinine ratio at 4 h (D/P4) (r = 0.422, P = 0.015) and mass transfer area coefficient (MTAC) of creatinine (r = 0.457, P = 0.008). The PDE BMP-7 level by ELISA also had marginal correlation with D/P4 (r = 0.287, P = 0.072) and MTAC creatinine (r = 0.287, P = 0.073), although the result did not reach statistical significance. For the subgroup of patients who remained free of peritonitis, the PDE BMP-7 level by ELISA had significant correlation with the change in D/P4 (r = 0.441, P = 0.017) and MTAC creatinine in 52 weeks (r = 0.415, P = 0.025). The PDE BMP-7 level remained independently associated with the change in peritoneal transport adjusting for age, sex, serum C-reactive protein and PDE transforming growth factor-beta level. In patients who had peritonitis during the study period, the PDE BMP-7 level did not affect the change in peritoneal transport. Conclusion. We find that the peritoneal BMP-7 level correlates with peritoneal transport characteristics, and a high PDE BMP-7 level is associated with a gradual increase in peritoneal transport parameters with time. It remains unclear, however, whether this effect is beneficial, and the therapeutic role of exogenous BMP-7 on peritoneal transport requires a further study.

TGF-β1 Gene Polymorphisms and Peritoneal Equilibration Test Results in CAPD Patients

Transforming growth factor-β1 (TGF-β1) stimulates the expression of collagen mRNA in cultured human peritoneal mesangial cells, which may predispose them to developing peritoneal fibrosis. Polymorphisms in the signal sequence genetically may be responsible for increased TGF-β1 production (i.e., a substitution at amino acid position 10 and 25, +869 Leu10–Pro and +915 Arg25–Pro, respectively). The aim of this study was to find out whether there is any relation between peritoneal equilibration test (PET) results and TGF-β1 gene polymorphism. Thirty-two CAPD patients and 72 healthy subjects were included into the study. Each CAPD patient had undergone two PET with a two-year interval. The patients were classified according to the results of a baseline PET as high (high-high average) and low (low-low average) transporters. In high transporters group (n = 20), the genotype frequencies were found as 45% Leu/Leu, 55% Leu/Pro for codon 10; and 85% Arg/Arg, 15% Arg/Pro for codon 25. In low transporters group (n = 12), the genotype frequencies were detected as 66.7% Leu/Leu and 33.3% Leu/Pro for codon 10; and 83.3% Arg/Arg, 16.7% Arg/Pro for codon 25. The distribution of the TGF-β1 genotypes in our control population was compatible with a Hardy-Weinberg equilibrium. We found no relation between TGF-β1 genotypes and peritoneal transport group (χ2 test, p > 0.5). There was no relation between TGF-β1 genotype and longitudinal change in peritoneal transport. This study is the first study analyzing the possible link between TGF-βl gene polymorphisms and the characteristics of peritoneal transport and longitudinal change of peritoneal transport characteristics in CAPD patients. Further work is needed to clarify the functional importance of these two polymorphisms in TGF-β1 production and in the development of peritoneal fibrosis.

Impact of ACE Inhibitors and AII Receptor Blockers on Peritoneal Membrane Transport Characteristics in Long-Term Peritoneal Dialysis Patients

Long-term peritoneal dialysis (PD) may lead to peritoneal fibrosis and ultrafiltration failure. The latter occurs due to high solute transport rates and diabetiform peritoneal sclerosis. Angiotensin-II (AII) is known to be a growth factor in the development of fibrosis and a number of animal studies have shown it likely that inhibiting the effects of AII by angiotensin-converting enzyme (ACE) or angiotensin receptor blocker (ARB) will attenuate these complications. To investigate the effects of ACE/AII inhibitors in long-term PD patients. We analyzed data from 66 patients treated with PD therapy at our center for at least 2 years, during which time at least 2 standard peritoneal permeability analyses (SPAs) were performed. 36 patients were treated with ACE/AII inhibitors (ACE/ARB group); the other 30 received none of the above drugs during the entire follow-up (control group). The two groups were compared with respect to changes in peritoneal transport over the follow-up time. A significant difference in time course of peritoneal transport was found between the 2 groups: in the ACE/ARB group, small solute transport had decreased, while it had increased in the control group. This finding was confirmed by analysis using mixed model for repeated measures. The value of mass transfer area coefficient of creatinine was influenced by the duration of PD therapy (p = 0.017) and this interaction was different with respect to use of ACE/AII inhibitors (p = 0.037). The trend was not found in protein clearances or fluid kinetics. Our findings suggest that ACE/AII inhibition is likely to prevent the increase in mass transfer area coefficients that occurs in long-term PD, which is in line with results of experimental animal studies.

Longitudinal changes of solute transport in peritonitis-free peritoneal dialysis patients.

The aim of this study was to evaluate the longitudinal changes in peritoneal transport in patients on long-term, peritonitis-free, continuous ambulatory peritoneal dialysis (CAPD) therapy. Results were longitudinally recorded for the standard peritoneal equilibration test (PET) in 76 consecutive, nondiabetic, adult patients from the beginning of CAPD therapy until their first episodes of peritonitis, abdominal surgery, or any cause of drop out. The PET results were evaluated once annually using the dialysate-to-plasma ratio of creati-nine (D/PCr) and the dialysate-to-instilled dextrose ratio (D4/D0) at 4 hours after beginning dialysis. A total of 168 PET results were obtained. A statistically significant tendency toward decreased D/PCr and increased D4/D0 values over time for up to 3 years was found. This study shows a tendency toward progressive decline in small molecular transport over time in nondiabetic patients with uneventful CAPD therapy. Sequential PET follow-up cannot be overlooked in peritonitis-free CAPD patients.

Longitudinal Study of Peritoneal Membrane Function in Continuous Ambulatory Peritoneal Dialysis: Relationship with Peritonitis and Fibrosing Factors

The peritoneal equilibration test (PET) is a useful assessment of peritoneal function in continuous ambulatory peritoneal dialysis (CAPD) patients. However, the natural course of longitudinal change in peritoneal transport is not well defined. We studied 105 unselected CAPD patients. Average age at enrollment was 50.7 +/- 11.3 years. A PET was performed at enrollment. Peritoneal transport was expressed as dialysate-to-plasma creatinine ratio at 4 hours (DIP). Fibrosing factors and mesothelial cell markers, including TGFbeta, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), hyaluronan, and cancer antigen 125 (CA125), were measured in overnight peritoneal dialysate effluent (PDE). Patients were followed for two years. Peritonitis episodes were recorded. Severe peritonitis was defined as an episode that required catheter removal or antibiotic therapy for more than 3 weeks. After two years, 75 patients were still alive and on CAPD. The PET was repeated in 64 patients, of whom 35 were male and 9 had diabetes. The change in D/P over two years was represented as AD/P. No significant change in peritoneal transport was seen after two years (D/P: 0.56 +/- 0.12 vs 0.55 +/- 0.13). A centripetal pattern of change in D/P was observed. The deltaD/P had normal distribution and was inversely correlated with D/P at baseline (r = -0.427, p < 0.005). Both results suggest a regression-to-mean phenomenon. The deltaD/P had no significant correlation with the total number of peritonitis episodes (Spearman r = 0.052, p = 0.74), but after severe peritonitis, affected patients had higher deltaD/P than patients who experienced no severe infection (0.040 +/- 0.136 vs -0.032 +/- 0.120, p < 0.05). For patients with no episodes of severe peritonitis (n = 47), deltaD/P was weakly correlated with baseline TGFbeta level (r = -0.506, p < 0.01). No correlation was seen between the levels of other fibrosing factors and change in peritoneal transport. Our findings suggest that the centripetal change of peritoneal transport probably reflects a regression-to-mean phenomenon. Peritoneal transport increases after severe peritonitis. The role of TGFbeta levels in PDE with regard to longitudinal change in peritoneal transport requires further study.

Effect of blood perfusion on diffusive transport in peritoneal dialysis

Diffusive transport between blood and dialysate during peritoneal dialysis is evaluated in clinical and experimental studies by the diffusive mass transport coefficient, KBD. This global parameter depends on the local diffusive characteristics of the blood capillary wall (permeability) and the tissue, as well as on the density and distribution of capillaries within the tissue. It also depends on the rate of delivery (or washout) of solutes from the tissue with blood flow, that is, on the rate of tissue perfusion. However, the role of blood perfusion in peritoneal transport has not been theoretically evaluated. The relationship between the local characteristics of the peritoneal tissue and the global diffusive mass transport coefficient was studied using a new extended version of the distributed model for peritoneal transport, which included the effect of tissue perfusion and capillary surface area on the blood-tissue transport. The solute concentration profiles within the tissue were found to depend on the solute penetration depth, which is equal to the square root of the ratio of the solute diffusivity in tissue to the solute clearance from the capillary bed to tissue. It was shown that KBD might be interpreted as the dialysance of a capillary bed of a characteristic size that would be immersed directly in dialysate. A definition of the effective peritoneal blood flow (EPBF; the blood flow within the tissue layer) was formulated, and it was shown that EPBF depends on the local transport characteristics for the solute. Assuming typical values of the model parameters (known from physiological studies), the values of KBD and EPBF for urea, creatinine, glucose, and CO2 were calculated and compared with the measured values with good qualitative agreement. The transient initial increase of KBD values observed at the beginning of the peritoneal dialysis dwell was interpreted as a transient sixfold increase in tissue perfusion and a twofold increase in the capillary surface area. The distributed model can be useful as a theoretical tool for detailed physiological interpretations of changes in peritoneal transport associated with changes in peritoneal microcirculation and structure of the interstitium.

Effects of Peritoneal Rest on Peritoneal Transport and Peritoneal Membrane Thickening in Continuous Ambulatory Peritoneal Dialysis Rats

To evaluate the effects of peritoneal rest on peritoneal transport and morphology in a rat model of peritoneal dialysis. Twenty-four rats (Sprague-Dawley, male, 250-300 g) were divided into three groups: group 1 (control, n = 6) without dialysis, group 2 (n = 9) sacrificed immediately after 3 weeks of dialysis, and group 3 (n = 9) sacrificed after 4 weeks of peritoneal rest after 3 weeks of dialysis. Both dialysis groups were dialyzed twice daily with an intraperitoneal instillation volume of 25 mL of 3.86% dextrose solution for 3 weeks. Peritonitis was induced by supplementing the dialysis fluid with lipopolysaccharide (5 microg/mL) on days 8, 10, and 12 in both dialysis groups. Peritoneal equilibration tests were performed on each animal at baseline. The equilibration tests were repeated at the 4th and the 8th week of dialysis. Morphometric analyses of the peritoneal membrane were carried out in tissue specimens obtained at the time of sacrifice. The D/D0 ratio for glucose at two hours in groups 2 and 3 at the beginning of week 4 was significantly lower than at baseline, indicating an increase in peritoneal permeability to glucose after 3 weeks of dialysis. D/D0 in group 3 at the beginning of week 8, after 4 weeks of peritoneal rest, was significantly higher than at week 4. The drain volume in groups 2 and 3 at week 4 was significantly lower than at baseline; however, the drain volume in group 3 at week 8 was significantly higher than at week 4. The thickness of the parietal peritoneal membrane in group 3 was significantly greater than in group 1 and less than in group 2 (group 1, 11.4+/-7.6 microm; group 2, 37.5+/-18.4 microm; group 3, 21.4+/-12.1 microm). Peritoneal rest improves ultrafiltration in rats by decreasing the hyperpermeability of glucose and also reduces the degree of peritoneal thickening. These data suggest that dialysis-induced changes in peritoneal transport and morphology are reversible under the conditions of peritoneal rest in this experimental model.

The Effect of a Nitric Oxide Inhibitor (L-Name) on Peritoneal Transport during Dialysis in Rats

To assess the effect of an inhibitor of nitric oxide synthesis [N(G)-nitro-L-arginine methyl ester (L-NAME)] on peritoneal transport during peritoneal dialysis (PD) and peritonitis in rats. The authors studied peritoneal transport of small and large solutes, and net ultrafiltration (UF) in rats during PD with Dianeal 3.86 (Baxter, McGaw Park, IL, U.S.A.). They evaluated the effect of L-NAME used as an additive to dialysis fluid in concentrations 0.5-5 mg/mL on peritoneal transport of small and large molecules and on transperitoneal UF. In addition, they studied the effect of L-NAME (5 mg/mL) during acute peritonitis induced by lipopolysaccharides (5 microg/mL) given intraperitoneally. The addition of L-NAME to dialysis fluid increased the selectivity of the peritoneum and net UF during dialysis. Lipopolysaccharides used as an additive to the dialysis fluid, together with L-NAME, did not induce changes in transperitoneal transport of small and large solutes and did not cause a significant decline in net UF. L-NAME given intraperitoneally reduced both local and systemic production of nitric oxide, which might explain its effects on peritoneal transport. Nitric oxide is an important mediator of changes in peritoneal transport and its effect is especially significant during peritonitis.

24-Hour Dialysate Collection for Determination of Peritoneal Membrane Transport Characteristics: Longitudinal Follow-Up Data for the Dialysis Adequacy and Transport Test (Datt)

To determine the ability of the dialysis adequacy and transport test (DATT) to monitor changes in peritoneal transport characteristics over time. University-based peritoneal dialysis program. One hundred patients on continuous ambulatory peritoneal dialysis who underwent 226 simultaneous DATTs and peritoneal equilibration tests (PET). Retrospective analysis of DATT and PET data. The mean 24-hour dialysate-to-plasma creatinine (cr) concentration ratio (D/P cr) from the DATT was 0.70 +/- 0.10, and the mean four-hour D/P cr from the PET was 0.68 +/- 0.10. The correlation coefficient between the four-hour and 24-hour D/P cr was 0.81, and the standard error of estimate was 0.065. The mean (+/- SD) difference between the four-hour and 24-hour D/P cr was 0.023 +/- 0.061. Fifty-eight patients had two or more sequential DATTs and PETs. For these 94 sets of sequential DATTs and PETs, the mean (+/- SD) difference between the change in the four-hour D/P cr and the change in the 24-hour D/P cr was 0.020 +/- 0.024, and the standard error of estimate was 0.064. In 17 patients a change in dwell volume from 2.0 L to 2.5 L occurred between the first and second measures of peritoneal membrane transport characteristics. The mean (+/- SD) difference between the change in the four-hour D/P cr and the change in the 24-hour D/P cr was 0.036 +/- 0.055, and the standard error of estimate was 0.087. The DATT can be used to monitor for changes in peritoneal transport over time. It should not be used in patients receiving cycler therapy or in patients whose dwell times and dextrose concentrations vary markedly from day to day.

Changes in Peritoneal Transport during the First Month of Peritoneal Dialysis

To determine if peritoneal transport characteristics change during the initial month of peritoneal dialysis. Retrospective review of peritoneal equilibration test (PET) results in patients who received their first PET during the first two weeks of peritoneal dialysis (early PET group) versus patients who received their first PET between four and 28 weeks after the initiation of dialysis (late PET group). The initial PET values were compared to subsequent PET results obtained approximately seven months after the initial PET. Peritoneal dialysis unit of a tertiary medical center. PET results and calculated mass transfer area coefficient (MTAC) values. Thirty-four peritoneal dialysis patients in the early PET group and 17 peritoneal dialysis patients in the late PET group. In the early PET group, there was a statistically significant increase from the initial to follow-up values for both dialysate-to-plasma (D/P) creatinine and MTAC creatinine (p < 0.01) as well as a significant decrease for four-hour dialysate to initial dialysate ratios (D/Do) glucose (p = 0.08) and MTAC glucose (p < 0.05). In the late PET group, there was no significant change in any of these parameters with time. However, in the late PET group, there was a significant decrease in D/P urea values with time (p < 0.01), but not with MTAC urea. In addition, there were no differences over time in either group for serum albumin or hematocrit values. During the first two weeks of peritoneal dialysis, there tends to be a change in peritoneal transport characteristics in some patients. PET data obtained during this time period should be interpreted as preliminary.

Clinical Implications of Membrane Transport Characteristics on the Adequacy of Fluid and Solute Removal

It is important to identify the peritoneal transport characteristics of each patient and to guide the peritoneal therapy accordingly. High transporters on CAPD are prone to protein malnutrition because of increased protein losses and suppression of appetite with excessive carbohydrate loading from the peritoneal cavity. Anephric high transporters often do better on short-cycle therapies. Anephric low transporters of large size cannot readily meet clearance targets on standard peritoneal dialysis prescriptions. In patients with low rates of peritonitis, changes in peritoneal dialysis prescriptions are more commonly dictated by changes in residual renal function rather than changes in peritoneal transport.

Changes in Peritoneal Transport following the Use of Intraperitoneal Gentamicin

Changes in Peritoneal Transport following the Use of Intraperitoneal Gentamicin