Peritoneal Transport Parameters Research Articles

#3270 TRANSPORT AND HYDROLYSIS OF ICODEXTRIN DURING PERITONEAL DIALYSIS

Abstract Background and Aims α-amylase, an enzyme present in plasma and peritoneal tissue, takes part in the process of starch digestion. During peritoneal exchange with icodextrin-based solution, polysaccharide chains are hydrolysed to shorter oligosaccharide chains, influencing osmotic properties of peritoneal dialysate. We estimated peritoneal transport parameters and compared them with hydrolytic clearances using a new model that takes into consideration absorption of icodextrin from the peritoneal cavity and its degradation by α-amylase. Method Frequent dialysate and blood samples were taken in 11 patients (8 icodextrin-naïve, 3 icodextrin-exposed) undergoing 16-hour dwell studies with icodextrin-based dialysis solution and labeled serum albumin (RISA) added as a volume marker. Using data on the intraperitoneal volume and dialysate and blood concentrations of glucose, urea, creatinine, and 7 icodextrin molecular weight (MW) fractions (glucose polymer size classes) and dialysate concentrations of α-amylase the extended three-pore model was applied to estimate individual parameters related to the peritoneal transport induced by dialysis and to hydrolysis of icodextrin by α-amylase. The following MW cut-off values were assumed for icodextrin fractions: up to 1.08, 4.44, 9.89, 21.4, 43.5, 66.7 and over 66.7 kDa, called Fractions 1–7, respectively. The hydrolytic clearances were defined as rate at which dialysate volume is cleared of the fraction by hydrolysis. The time-dependent hydrolytic clearances of icodextrin fractions were calculated and compared with diffusive ones. For the first time the extended three-pore model was validated not only with respect to the peritoneal transport of water and small solutes but also regarding concentration of icodextrin fractions. Results Mean measured and simulated dialysate to plasma concentration ratios for glucose, urea and creatinine are presented in Figure 1, left panel. The peritoneal kinetic of icodextrin (dialysate concentrations of each fraction over its initial concentration) is presented for mean measured data and numerical simulation results in Figure 1, right panel. The results showed that the model provides accurate (mean relative error less than 7%) description of individual patient peritoneal transport kinetics including that of icodextrin fractions in peritoneal dialysate. The comparison of hydrolytic clearances (H) with diffusive transport parameters for icodextrin fractions (PS, reflecting the maximal rates of their clearance by diffusion) showed that in case of shorter polymers (Fractions 1–3) diffusive clearances were higher or similar to hydrolytic ones over the whole dwell time. In case of Fractions 4 and 5, the initial domination of PS slowly decreased during the dwell time, being dominated by hydrolysis processes at the end of the exchange, at least partly due to the changes of intraperitoneal volume and α-amylase concentration. In case of polysaccharides from Fractions 6 and 7, their hydrolytic clearances remained higher than the diffusive ones during whole dwell time. Interestingly, the obtained values of H in icodextrin-exposed patients typically remained below 1.2 mL/min except for Fraction 6, for which H increased from initial value of 0.83±0.30 to 1.43±0.64 mL/min at the end of the peritoneal dwell. On the other hand, the estimated final values of H in icodextrin-naïve patients were on average higher than 1.2 mL/min in all fractions except Fractions 4 and 5. Conclusion The model provided accurate description of peritoneal transport and icodextrin hydrolysis during long icodextrin dwells. The model showed that hydrolytic processes dominate over diffusive ones during whole dwell time in case of Fractions 6 and 7, whereas diffusive processes dominate for Fractions 1–3.

#4387 LIQUID BIOPSY IN PATIENTS TREATED WITH BIOCOMPATIBLE PERITONEAL DIALYSIS FLUIDS – ITS RELATIONSHIP WITH CYTOLOGICAL AND HISTOLOGICAL FINDINGS

Abstract Background and Aims Peritoneal fibrosis can limit long term peritoneal membrane function in peritoneal dialysis (PD) patients. It has been related to bioincompatible PD fluids and peritoneal infections. There are no prospective studies regarding correlation between effluent biomarkers and peritoneal biopsy findings. Our aim was to study the possible relation of peritoneal effluent biomarkers and peritoneal morphology alterations. Method Multicenter prospective study in a cohort of stable PD patients treated with biocompatible PD fluids who received a kidney transplant. We collected in each patient peritoneal biopsy samples and peritoneal effluent fluid. We analyzed the relation between effluent biomarkers, phenotype of mesothelial cells (MC) cultured ex vivo, and peritoneal biopsy parameters (mesothelial integrity, fibrosis and hyalinizing vasculopathy). We compared them with patient characteristics, including peritoneal transport parameters. The biomarkers tested were Collagen-1 (COL-1), Fibronectin (FN), Collagen-13 (COL-13), Interleukin-6 (IL-6), Trombospondin-1, Cadherin 13 (CDH-13), CA-125, Gremlin-1 (GREM-1), Matrix metalloproteinase 2 (MMP-2), CC chemokine ligand 18 (CCL18), Plasminogen activator inhibitor 1 (PAI-1) and Vascular endothelial growth factor A (VEGF-A). Results Forty patients were included (mean age 54.5±15 years, 64% male, 24.1% diabetics). Mean time on PD was 25.5±27 months, 62.1% were on automated PD (APD) and 17.2% had prior peritonitis episodes. A normal MC culture phenotype was observed in 78% of patients. In peritoneal biopsies samples we found partial or total mesothelium preservation in 39%, submesothelial thickness in 42% and vasculopathy in 14% of cases. Effluent PAI-1 levels were significantly lower in patients with mesothelial cell loss than in those with mesothelial preservation (21.62 vs. 38.59 pg/ml respectively; p = 0.031). Patients with peritoneal fibrosis showed significantly higher effluent CDH-13 levels (3.51 vs. 2.32 pg/ml; p = 0.048) and supernatant PAI-1 levels (1183 vs. 72.73; p = 0.000) than those without fibrosis. No other statistical differences were found in other biomarkers analysed. Conclusion Most patients treated with biocompatible peritoneal dialysis fluids showed normal mesothelial cell phenotype in peritoneal effluent culture. Lower PAI-1 effluent levels were associated with mesothelial cell loss and higher effluent CDH-13 levels were related to peritoneal fibrosis.

Inflammatory chemokine (C-C motif) ligand 8 inhibition ameliorates peritoneal fibrosis.

Peritoneal fibrosis (PF) is an irreversible complication of peritoneal dialysis (PD) that leads to loss of peritoneal membrane function. We investigated PD effluent and serum levels and the tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with PD. Additionally, we investigated their association with PF in a mouse model. Eighty-two end-stage renal disease (ESRD) patients with PD were examined. CCL8 levels were measured via enzyme-linked immunosorbent assays in PD effluents and serum and analyzed with peritoneal transport parameters. Human peritoneal mesothelial cells (hPMCs) were obtained from the PD effluents of 20 patients. Primary cultured hPMCs were treated with recombinant (r) transforming growth factor (TGF)-β, and CCL8 expression was assessed via western blotting. As the duration of PD increased, the concentration of CCL8 in PD effluents significantly increased. Correlations between peritoneal transport parameters and dialysate CCL8 levels were observed. Western blotting analysis showed that CCL8 was upregulated via rTGF-β treatment, accompanied by increases in markers of inflammation, fibrosis, senescence, and apoptosis in hPMCs after induction of fibrosis with rTGF-β. Anti-CCL8 monoclonal antibody (mAb) treatment suppressed the rTGF-β-induced increase in all analyzed markers. Immunohistochemical analysis revealed that CCL8 along with fibrosis- and inflammation-related markers were significantly increased in the PF mouse model. Functional blockade of CCL8 using a CCR8 inhibitor (R243) abrogated peritoneal inflammation and fibrosis in vivo. In conclusion, high CCL8 levels in PD effluents may be associated with an increased risk of PD failure, and the CCL8 pathway is associated with PF. CCL8 blockade can ameliorate peritoneal inflammation and fibrosis.

On the change of transport parameters with dwell time during peritoneal dialysis.

The transitory change of fluid and solute transport parameters occurring during the initial phase of a peritoneal dialysis dwell is a well-documented phenomenon; however, its physiological interpretation is rather hypothetical and has been disputed. Two different explanations were proposed: (1) the prevailing view-supported by several experimental and clinical studies-is that a vasodilatory effect of dialysis fluid affects the capillary surface area available for dialysis, and (2) a recently presented alternative explanation is that the molecular radius of glucose increases due to the high glucose concentration in fresh dialysis fluid and that this change affects peritoneal transport parameters. The experimental bases for both phenomena are discussed as well as the problem of the accuracy necessary for a satisfactory description of clinical data when the three-pore model of peritoneal transport is applied. We show that the correction for the change of transport parameters with dwell time provides a better fit with clinical data when applying the three-pore model. Our conclusion is in favor of the traditional interpretation namely that the transitory change of transport parameters with dwell time during peritoneal dialysis is primarily due to the vasodilatory effect of dialysis fluids.

P1149PERITONEAL MEMBRANE CHARACTERISTICS OVER TIME: A LONGITUDINAL STUDY

Abstract Background and Aims Modified PET (use of 3.86% glucose dialysate instead of 2.27%) and temporal drainage at one hour allows a more complete study of peritoneal membrane transport, as it provides information about sodium sieving, free water transport (FWT) and ultrafiltration failure (UFF). Longitudinal data using this PET are sporadic. Aims of our study were a) longitudinal follow-up of the membrane function using modified PET b) evaluation of UFF and association with clinical and membrane characteristics. Method We analyzed all modified PET tests performed in our unit during the last 9 years. Patients who underwent the first test during the first year of treatment and then once a year were included. We estimated classic peritoneal transport parameters like D/P creatinine, D/D0 glucose and ultrafiltration (UF) at 4 hours. Moreover we calculated sodium seiving expressed as Dip/DPNa= (Dialysate sodium time 0/plasma sodium)-(Dialysate sodium time 1 hour/plasma sodium)], sodium removal (in one hour) and FWT. We collected clinical and lab data of the patients too. Results A total of 219 PETs were performed in 85 PD patients, (median age 64 years (range 18-45). The baseline membrane characteristics of the patients were: DP creatinine=0.74±0.11, D/D0glucose=0.28±0.08, DipDPNa=0.05±0.04, sodium removal=29,804 ±26,894 (mmol/L), FWT=214.9±194.7 ml and UF =655.1±265.5 ml. On multivariate regression analysis D/P creatinine, FWT and sodium removal were significant independent covariates accounting for 50% of the variability of ultrafiltration . The patients were followed-up for a median of 36 months (range 2.4-143).For the repeated measurements, the analysis showed that the observed values of D/Pcre,D/D0, Dip/DPNa, FWT and UF remained rather stable across the different time measurements. During the study, 23 out of 85 pts developed peritoneal UF failure (UFF). Analysis was performed using univariate random effects logistic time-series models and only D/D0 (OR=0.84, P=0.001), D/P Cre (OR=1.15, p<0.001), urine volume (OR=1.26, p=0.027) and sodium removal (OR=0.99, p=0.003) were significantly associated with relative risk of UFF development. Conclusion Surprisingly, our patients present a stable membrane function over time. Possible explanations could be the low peritonitis rate and strict use of hypertonic glucose dialysates. Ultrafiltration failure was correlated with higher D/P creatinine and lower D/D0 glucose values, higher baseline urine volume and lower sodium sieving.

Dialysate copeptin and peritoneal transport in incident peritoneal dialysis patients

PurposeSystemic and intraperitoneal inflammation are characteristic features of patients with end-stage renal disease undergoing chronic peritoneal dialysis (PD). Arginine vasopressin (AVP) and its surrogate marker copeptin play important roles in many pathophysiological processes in chronic kidney disease. The aim of this study was to assess if copeptin concentrations in plasma and dialysate were related to peritoneal transport parameters and residual renal function (RRF) in incident PD patients.MethodsIn 37 clinically stable incident PD patients (mean age 50 years, 68% women, 32% diabetes), a 4 h peritoneal equilibration test (PET) was performed 4–6 weeks after the onset of PD. Plasma (at 2 h of PET) and dialysate (at 4 h) concentrations of copeptin, high-sensitivity C-reactive protein and interleukin-6 (IL-6) were determined.ResultsPlasma (80.7 ± 37.3 pg/mL) and dialysate (33.2 ± 18.0 pg/mL) concentrations of copeptin were correlated (Rs = 0.52, p = 0.001). Plasma and dialysate copeptin concentrations were negatively correlated with renal function as assessed by renal Kt/V (Rs = − 0.38; p = 0.021 and Rs = − 0.33; p = 0.047, respectively). At PET, dialysate copeptin negatively correlated with D/P creatinine (Rs = − 0.35, p = 0.033), and positively with D/D0 glucose (Rs = 0.33, p = 0.045) and ultrafiltration (Rs = 0.37, p = 0.024). Multivariate analysis showed that low dialysate copeptin (β = –0.30, p = 0.049) and high dialysate IL-6 (β = + 0.40, p = 0.012) were independent determinants of higher D/P creatinine.ConclusionsDialysate copeptin was negatively associated with D/P creatinine in incident PD patients suggesting a potential influence of copeptin or AVP on peritoneal solute transport rate that might involve vasoactive mechanisms.

Effects of Oral Paricalcitol and Calcitriol Treatment on Peritoneal Membrane Characteristics of Peritoneal Dialysis Patients - A Pilot Study.

Long-term peritoneal dialysis (PD) is frequently complicated by technique failure preceded by peritoneal remodeling. Vitamin D has potent immunomodulatory characteristics: anti-inflammatory, anti-angiogenic, anti-fibrotic properties, and influences on the macrophage phenotype. Little is known about the relation between pleiotropic effects attributed to vitamin D3 and the peritoneal membrane and what is the most appropriate vitamin D sterol in prevention of peritoneal remodeling in PD patients. Animal studies have suggested that paricalcitol has advantageous effects: decrease in plasma markers of inflammation, less peritoneal fibrosis, less pronounced PD-induced omental angiogenesis, and prevention of loss of ultrafiltration. We investigated whether paricalcitol is advantageous over calcitriol in PD patients. A multicenter open-label 1:1 randomized non-blinded clinical pilot study enrolled prevalent continous ambulatory PD (CAPD) patients for a period of 6 months comparing paricalcitol with calcitriol. All patients were treated with biocompatible PD fluids. The primary endpoint was peritoneal transport parameters, exploratory endpoints were biomarkers of peritoneal damage and cell analysis (including M1/M2 macrophages), and safety endpoints were metabolic parameters. Twenty-seven patients were included. Fourteen were randomized to treatment with paricalcitol. There was no difference in peritoneal transport parameters between the groups. We found similar Kt/V, D/P creatinine, D/D0 glucose, ultrafiltration, residual renal function and 24-h urine volume during the study. There was no difference in biomarker concentrations in peritoneal effluents, and no difference in leucocyte differentiation or mesothelial cells between the groups at any time point. Parathyroid hormone (PTH) levels decreased after administration of calcitriol after 12 and 24 weeks compared with baseline (p = 0.001; p = 0.025). Parathyroid hormone levels in the paricalcitol group did not change significantly. In this pilot study we investigated the effect of active vitamin D in PD patients. We found no specific benefit of active vitamin D3 in vitamin D3-sufficient PD patients. Additional studies in preferably incident patients, with an adequate PTH suppression in the intervention groups and during a longer period, are required to test the beneficial effects of active vitamin D3 over no treatment and to investigate whether in 25(OH)D3-deficient PD patients the type of active vitamin D3 matters.

Changes of peritoneal transport parameters with time on dialysis: assessment with sequential peritoneal equilibration test.

Sequential peritoneal equilibration test (sPET) is based on the consecutive performance of the peritoneal equilibration test (PET, 4-hour, glucose 2.27%) and the mini-PET (1-hour, glucose 3.86%), and the estimation of peritoneal transport parameters with the 2-pore model. It enables the assessment of the functional transport barrier for fluid and small solutes. The objective of this study was to check whether the estimated model parameters can serve as better and earlier indicators of the changes in the peritoneal transport characteristics than directly measured transport indices that depend on several transport processes. 17 patients were examined using sPET twice with the interval of about 8 months (230 ± 60 days). There was no difference between the observational parameters measured in the 2 examinations. The indices for solute transport, but not net UF, were well correlated between the examinations. Among the estimated parameters, a significant decrease between the 2 examinations was found only for hydraulic permeability LpS, and osmotic conductance for glucose, whereas the other parameters remained unchanged. These fluid transport parameters did not correlate with D/P for creatinine, although the decrease in LpS values between the examinations was observed mostly for patients with low D/P for creatinine. We conclude that changes in fluid transport parameters, hydraulic permeability and osmotic conductance for glucose, as assessed by the pore model, may precede the changes in small solute transport. The systematic assessment of fluid transport status needs specific clinical and mathematical tools beside the standard PET tests.

Relationship between bioimpedance-determined body composition and peritoneal transport in peritoneal dialysis.

In peritoneal dialysis (PD) patients, body fluid homeostasis is dependent on peritoneal elimination of water and solutes. Patients with less favorable peritoneal transport parameters should be more overhydrated. Despite this, the association between faster transport and overhydration (OH) is weak, and the factors that influence hydration status are still poorly characterized. Modified peritoneal equilibration tests (PET) offer us new parameters that might correlate better with hydration status, like free water transport (FWT). The aim of this study was thus to establish the relationships between new peritoneal transport parameters and body composition parameters estimated by bioimpedance spectroscopy (BIS). Prospective observational study on incident PD patients with a baseline and 1-year follow-up evaluation. 61 patients were included in the baseline evaluation, 19 of whom had a 1-year follow-up evaluation; 67.2% were fluid overloaded. There was a negative correlation between D/P creatinine and FWT (r = -0.598, p = 0.000). The fraction of FWT was negatively correlated with OH (r = -0.302, p = 0.018). Peritoneal protein losses (PPL) were also correlated with OH (r = 0.287, p = 0.028). There were no significant differences in OH according to small-solute transport status or fluid output parameters. After 1 year, we observed a significant worsening of renal function and an improvement in 24-hour ultrafiltration (UF) and hydration status, but we detected no differences in peritoneal transport of water or solutes that could explain these changes. There is a poor relationship between kidney/peritoneal function parameters and body composition parameters. The fraction of FWT and PPL may be underestimated markers of peritoneal health and of its contribution to the hydration status.

Sustained low peritoneal effluent CCL18 levels are associated with preservation of peritoneal membrane function in peritoneal dialysis.

Peritoneal membrane failure (PMF) and, ultimately, encapsulating peritoneal sclerosis (EPS) are the most serious peritoneal dialysis (PD) complications. Combining clinical and peritoneal transport data with the measurement of molecular biomarkers, such as the chemokine CCL18, would improve the complex diagnosis and management of PMF. We measured CCL18 levels in 43 patients’ effluent and serum at baseline and after 1, 2, and 3 years of PD treatment by retrospective longitudinal study, and evaluated their association with PMF/EPS development and peritoneal risk factors. To confirm the trends observed in the longitudinal study, a cross-sectional study was performed on 61 isolated samples from long-term (more than 3 years) patients treated with PD. We observed that the patients with no membrane dysfunction showed sustained low CCL18 levels in peritoneal effluent over time. An increase in CCL18 levels at any time was predictive of PMF development (final CCL18 increase over baseline, p = .014; and maximum CCL18 increase, p = .039). At year 3 of PD, CCL18 values in effluent under 3.15 ng/ml showed an 89.5% negative predictive value, and higher levels were associated with later PMF (odds ratio 4.3; 95% CI 0.90–20.89; p = .067). Moreover, CCL18 levels in effluent at year 3 of PD were independently associated with a risk of PMF development, adjusted for the classical (water and creatinine) peritoneal transport parameters. These trends were confirmed in a cross-sectional study of 61 long-term patients treated with PD. In conclusion, our study shows the diagnostic capacity of chemokine CCL18 levels in peritoneal effluent to predict PMF and suggests CCL18 as a new marker and mediator of this serious condition as well as a new potential therapeutic target.

Peritoneal dialysis effluent miR-21 and miR-589 levels correlate with longitudinal change in peritoneal transport characteristics

BackgroundThe role of microRNA (miRNA) in peritoneal fibrosis and longitudinal change in transport is uncertain. MethodsWe studied 80 new peritoneal dialysis (PD) patients. Peritoneal transport was determined by standard peritoneal equilibration test (PET) of creatinine at baseline. Based on published literature, PD effluent levels of 10 miRNA targets were quantified. PET and miRNA quantification were repeated one year later in 46 patients. ResultsBaseline PD effluent levels of all targets tested had modest but significant correlation with peritoneal transport parameters. PD effluent miR-21 and miR-589 levels correlated with dialysate-to-plasma creatinine concentration at 4h (D/P4) at baseline (r=0.377, p=0.001 and r=0.237, p=0.037, respectively) and after one year of PD (r=0.362, p=0.014 and r=0.402, p=0.007). The change in PD effluent −21 and miR-589 levels over one year correlated with the corresponding change in D/P4 (r=0.470, p=0.001 and r=0.479, p=0.002). The number of peritonitis episodes during follow up significantly correlated with the change in PD effluent miR-21 (r=0.387, p=0.009) and miR-589 (r=0.336, p=0.027) levels. There was no significant correlation between PD effluent miRNA level and ultrafiltration volume. ConclusionAmongst the 10 miRNA targets tested, miR-21 and miR-589 showed consistently significant relation with peritoneal transport. Further studies are needed to delineate their mechanisms of regulating peritoneal transport.

Peritoneal Fluid Transport rather than Peritoneal Solute Transport Associates with Dialysis Vintage and Age of Peritoneal Dialysis Patients.

During peritoneal dialysis (PD), the peritoneal membrane undergoes ageing processes that affect its function. Here we analyzed associations of patient age and dialysis vintage with parameters of peritoneal transport of fluid and solutes, directly measured and estimated based on the pore model, for individual patients. Thirty-three patients (15 females; age 60 (21–87) years; median time on PD 19 (3–100) months) underwent sequential peritoneal equilibration test. Dialysis vintage and patient age did not correlate. Estimation of parameters of the two-pore model of peritoneal transport was performed. The estimated fluid transport parameters, including hydraulic permeability (LpS), fraction of ultrasmall pores (α u), osmotic conductance for glucose (OCG), and peritoneal absorption, were generally independent of solute transport parameters (diffusive mass transport parameters). Fluid transport parameters correlated whereas transport parameters for small solutes and proteins did not correlate with dialysis vintage and patient age. Although LpS and OCG were lower for older patients and those with long dialysis vintage, αu was higher. Thus, fluid transport parameters—rather than solute transport parameters—are linked to dialysis vintage and patient age and should therefore be included when monitoring processes linked to ageing of the peritoneal membrane.

Ionic conductivity of peritoneal dialysate: a new, easy and fast method of assessing peritoneal membrane function in patients undergoing peritoneal dialysis.

Peritoneal membrane function can be assessed using the peritoneal equilibration test (PET) and similar tests, but these are almost always complicated to use, require a considerable amount of working time and their results cannot always be easily interpreted. Ionic conductivity is a measure of the ability of an electrolyte solution to conduct electricity. We tested the hypothesis that the ionic conductivity of peritoneal dialysate can be used to evaluate peritoneal membrane function in peritoneal dialysis patients. We measured the ionic conductivity and classic biochemical parameters of peritoneal dialysate in 69 patients during a modified PET and compared their ability to evaluate peritoneal membrane function and to diagnose ultrafiltration failure (UFF). Ionic conductivity was correlated well with classical parameters of peritoneal transport as glucose reabsorption of glucose (D/D0: r(2) = 0.62, P < 0.0001) and creatinine transport (D/PCreat: r(2) = 0.72, P < 0.0001). Twelve patients (17%) experienced UFF and, in them, the ionic conductivity area under the receiver-operating characteristic curve was 0.91 (95% confidence interval: 0.81-0.96) with sensitivity of 1.00 and specificity of 0.84 at a cut-off value of 12.75 mS/cm. These findings indicate that the ionic conductivity of peritoneal dialysate can be used as a new screening tool to evaluate peritoneal membrane function.

The First Peritonitis Episode Alters the Natural Course of Peritoneal Membrane Characteristics in Peritoneal Dialysis Patients

Little or no evidence is available on the impact of the first peritonitis episode on peritoneal transport characteristics. The objective of this study was to investigate the importance of the very first peritonitis episode and distinguish its effect from the natural course by comparison of peritoneal transport before and after infection. We analyzed prospectively collected data from 541 incident peritoneal dialysis (PD) patients, aged > 18 years, between 1990 and 2010. Standard Peritoneal Permeability Analyses (SPA) within the year before and within the year after (but not within 30 days) the first peritonitis were compared. In a control group without peritonitis, SPAs within the first and second year of PD were compared. SPA data included the mass transfer area coefficient of creatinine, glucose absorption and peritoneal clearances of β-2-microglobulin (b2m), albumin, IgG and α-2-macroglobulin (a2m). From these clearances, the restriction coefficient to macromolecules (RC) was calculated. Also, parameters of fluid transport were determined: transcapillary ultrafiltration rate (TCUFR), lymphatic absorption (ELAR), and free water transport. Crude and adjusted linear mixed models were used to compare the slopes of peritoneal transport parameters in the peritonitis group to the control group. Adjustments were made for age, sex and diabetes. Of 541 patients, 367 experienced a first peritonitis episode within a median time of 12 months after the start of PD. Of these, 92 peritonitis episodes were preceded and followed by a SPA within one year. Forty-five patients without peritonitis were included in the control group. Logistic reasons (peritonitis group: 48% vs control group: 83%) and switch to hemodialysis (peritonitis group: 22% vs control group: 3%) were the main causes of missing SPA data post-peritonitis and post-control. When comparing the slopes of peritoneal transport parameters in the peritonitis group and the control group, a first peritonitis episode was associated with faster small solute transport (glucose absorption, p = 0.03) and a concomitant lower TCUFR (p = 0.03). In addition, a discreet decrease in macromolecular transport was seen in the peritonitis group: mean difference in post- and pre-peritonitis values: IgG: -8 μL/min (p = 0.01), a2m: -4 μL/min (p = 0.02), albumin: -10 μL/min (p = 0.04). Accordingly, the RC to macromolecules increased after peritonitis: 0.09, p = 0.04. The very first peritonitis episode alters the natural course of peritoneal membrane characteristics. The most likely explanation might be that cured peritoneal infection later causes long-lasting alterations in peritoneal transport state.

Is the Systemic Microvascular Endothelial Glycocalyx in Peritoneal Dialysis Patients Related to Peritoneal Transport?

Background/Aims: The capillary wall coated by the endothelial glycocalyx is the main transport barrier during peritoneal dialysis (PD). Here, we investigated the relationships between measurements of the systemic endothelial glycocalyx and peritoneal transport in PD patients. Methods: We performed sidestream darkfield (SDF) imaging of the sublingual microvasculature in 15 patients, measured the perfused boundary region (PBR), which includes the permeable part of the glycocalyx, and calculated the estimated blood vessel density (EBVD). All patients underwent a peritoneal permeability analysis. Results: No relationships were present between the imaging and peritoneal transport parameters, neither in the group as a whole nor in fast transporters. In patients with nonfast peritoneal transport status, PBR had a negative relationship with EBVD and small solute transport, and a positive one with net ultrafiltration (NUF). The EBVD showed a positive correlation with glucose absorption and a negative one with NUF. We found no relationships with the peritoneal transport of albumin. Conclusions: No relationships are present between the systemic endothelial glycocalyx, which was assessed by SDF, and peritoneal transport. In nonfast transporters, a reduction in blood vessel density caused by endothelial glycocalyx alterations or a thicker permeable phase of the glycocalyx delaying the access of small solutes to the small pores may be important.

Can the three pore model correctly describe peritoneal transport of protein?

The three pore model (3PM) includes large pores for the description of protein leak to the peritoneal cavity during peritoneal dialysis. However, the reliability of this description has been not fully tested against clinical data yet. Peritoneal transport parameters were estimated using 3PM, extended 3p model (with estimation of fraction of large pores, ext3PM), ext3PM with modified size of pores and proteins (mext3PM), and simplified two pore (2PM, small and ultrasmall pores) models for 32 patients on peritoneal dialysis investigated using the sequential peritoneal equilibration test (consecutive peritoneal equilibration test [PET]: glucose 2.27%, 4 h, and miniPET: glucose 3.86%, 1 h). Urea, creatinine, glucose, sodium, phosphate, albumin, and IgM concentrations were measured in dialysis fluid and plasma. Ext3PM and mext3PM, with large pore fraction of about 0.14, provided a good description of fluid and small solute kinetics, but their predictions for albumin transport were less accurate. Two pore model precisely described the data on fluid and small solute transport. The 3p models could not describe the diffusive-convective transport of albumin as precisely as the transport of fluid, small solutes, and IgM. The 2p model (not applicable for proteins) was an efficient tool for modeling fluid and small solute transport.

Can Effluent Matrix Metalloproteinase 2 and Plasminogen Activator Inhibitor 1 be Used as Biomarkers of Peritoneal Membrane Alterations in Peritoneal Dialysis Patients?

Peritoneal effluent contains clinically relevant substances derived from intraperitoneal production or transperitoneal transport, or both. The glycoproteinase matrix metalloproteinase 2 (MMP-2) cleaves denatured collagen and complements other collagenases in the degradation of fibrillar collagens. Elevated intraperitoneal levels of plasminogen activator inhibitor 1 (PAI-1) have been demonstrated to be present in patients with intra-abdominal adhesions. The aim of the present study was therefore to investigate the potential for effluent MMP-2 and PAI-1 to be used as markers of the development of peritoneal alterations. In addition, MMP-2 was analyzed in previously frozen effluent samples from a uremic rat model, in which data concerning the severity of peritoneal fibrosis were available. This prospective, single-center cohort study included 86 incident peritoneal dialysis (PD) patients. All patients were treated solely with biocompatible dialysis solutions and underwent a standard peritoneal permeability analysis (SPA). The presence of local MMP-2 and PAI-1 production and the relationships between those markers and peritoneal transport parameters were analyzed. Furthermore, effluent interleukin 6 was analyzed as a marker of local inflammation. Median effluent levels of 21.4 ng/mL for MMP-2 and 0.9 ng/mL for PAI-1 were found. The median dialysate appearance rates were 218.8 ng/min for MMP-2 and 9.6 ng/min for PAI-1. Local peritoneal production averaged 90% of effluent MMP-2 concentration and 74% of effluent PAI-1 concentration. Furthermore, correlations between peritoneal transport parameters and MMP-2 and PAI-1 were observed. Longitudinal follow-up showed no change for MMP-2 (p = 0.37), but a tendency for PAI-1 to increase with the duration of PD (p < 0.001). In rats, a significant relationship was present between the extent of peritoneal fibrosis and the appearance rate of MMP-2 (r = 0.64, p = 0.03). The foregoing data illustrate the potential of effluent MMP-2 and PAI-1 as biomarkers of peritoneal modifications, especially fibrosis; however, the components of peritoneal transport and local production should be clearly distinguished in every patient.

Sequential peritoneal equilibration test: a new method for assessment and modelling of peritoneal transport

In spite of many peritoneal tests proposed, there is still a need for a simple and reliable new approach for deriving detailed information about peritoneal membrane characteristics, especially those related to fluid transport. The sequential peritoneal equilibration test (sPET) that includes PET (glucose 2.27%, 4 h) followed by miniPET (glucose 3.86%, 1 h) was performed in 27 stable continuous ambulatory peritoneal dialysis patients. Ultrafiltration volumes, glucose absorption, ratio of concentration in dialysis fluid to concentration in plasma (D/P), sodium dip (Dip D/P Sodium), free water fraction (FWF60) and the ultrafiltration passing through small pores at 60 min (UFSP60), were calculated using clinical data. Peritoneal transport parameters were estimated using the three-pore model (3p model) and clinical data. Osmotic conductance for glucose was calculated from the parameters of the model. D/P creatinine correlated with diffusive mass transport parameters for all considered solutes, but not with fluid transport characteristics. Hydraulic permeability (L(p)S) correlated with net ultrafiltration from miniPET, UFSP60, FWF60 and sodium dip. The fraction of ultrasmall pores correlated with FWF60 and sodium dip. The sequential PET described and interpreted mechanisms of ultrafiltration and solute transport. Fluid transport parameters from the 3p model were independent of the PET D/P creatinine, but correlated with fluid transport characteristics from PET and miniPET.

A Study of the Clinical and Biochemical Profile of Peritoneal Dialysis Fluid Low in Glucose Degradation Products

Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy, concerns remain regarding the bioincompatible nature of standard PD fluid (PDF). Short-term studies of new biocompatible PDFs low in glucose degradation products (GDPs) reveal divergent results with respect to peritoneal integrity. We studied 125 patients on maintenance PD who were assigned, by simple randomization, to receive either conventional or low-GDP PDF at PD initiation. Parameters of dialysis adequacy and peritoneal transport of small solutes were determined at initiation and after a period of maintenance PD at the time when serum and overnight effluent dialysate were simultaneously collected and assayed for various cytokines, chemokines, adipokines, and cardiac biomarkers. All patients were further followed prospectively for an average of 15 months from the day of serum and effluent collection to determine patient survival and cardiovascular events. Patients treated with conventional or low-GDP PDF were matched for sex, age, duration of dialysis, dialysis adequacy, and incidence of cardiovascular disease or diabetes. After an average of 2.3 years of PD treatment, the weekly total and peritoneal creatinine clearance, and the total and peritoneal Kt/V were comparable in the groups. However, urine output was higher in patients using low-GDP PDF despite there having been no difference between the groups at PD initiation. Patients using low-GDP PDF also experienced a slower rate of decline of residual glomerular filtration and urine output than did patients on conventional PDF. Compared with serum concentrations, effluent concentrations of tumor necrosis factor α, hepatocyte growth factor, macrophage migration inhibitory factor, interleukins 8 and 6, C-reactive protein, and leptin were found to be higher in both groups of patients after long-term PD, suggesting that the peritoneal cavity was the major source of those mediators. Compared with patients on low-GDP PDF, patients on conventional fluid showed elevated leptin and reduced adiponectin levels in serum and effluent. The effluent concentration of interleukin 8 was significantly lower in patients using low-GDP PDF. The survival rate and incidence of cardiovascular complications did not differ between these groups after maintenance PD for an average of 3.6 years. It appears that low-GDP PDF results in an improvement of local peritoneal homeostasis through a reduction of chronic inflammatory status in the peritoneum.

High-dose steroid treatment increases free water transport in peritoneal dialysis patients

The water channel aquaporin-1 (AQP1) is the molecular counterpart of the ultrasmall pore that mediates free water transport during peritoneal dialysis (PD). Proof-of-principle studies performed in rats have shown that treatment with corticosteroids upregulates the expression of AQP1 in the peritoneal capillaries, causing a significant increase in free water transport. Whether such a beneficial effect could be observed in end-stage renal disease patients treated by PD remains unknown. Peritoneal transport parameters were evaluated in three patients on PD, shortly before and after living-donor renal transplantation and treatment with high-dose methylprednisolone (1.0-1.2 g/m(2)). As compared with pre-transplantation values, the post-transplantation test revealed an ∼2-fold increase in the sodium sieving and ultrasmall pore ultrafiltration volume, suggesting an effect on AQP1 water channels. In contrast, there was no change in the parameters of small solute transport. The direct involvement of AQP1 in these changes is suggested by the expression of glucocorticoid receptors in the human peritoneum and the presence of conserved glucocorticoid response elements in the promoter of the human AQP1 gene.