Standard Peritoneal Permeability Analyses Research Articles

Low immunoglobulin G concentrations are not associated with an increased risk of peritoneal dialysis-related peritonitis.

Peritonitis is a common and severe complication of peritoneal dialysis (PD) and is associated with high morbidity and sometimes also with mortality. Identification of risk factors, as well as protective mechanisms for peritonitis, is important to reduce peritonitis-induced morbidity. According to the current literature, IgG concentrations might be associated with peritonitis in PD-treated patients. In this study, we aimed to investigate possible associations between dialysate or serum IgG concentration and peritonitis risk in a longitudinal cohort of PD-treated patients. We analyzed prospectively collected data obtained during the first standard peritoneal permeability analysis (SPA), performed in incident PD patients, aged >18 years who started PD treatment in our tertiary-care university hospital from January 1, 1994 until December 31, 2008. Patients were divided in groups according to dialysate or serum IgG concentrations and according to peritonitis incidence. A possible association between low dialysate or serum IgG concentrations and time to the first peritonitis episode was investigated using cox proportional hazard models. 120 patients were included in our analyses with a median follow-up time of 36 (16-92) months. No significant association between dialysate, nor serum IgG and time to peritonitis was found (HR 0.27 (95% CI 0.65-1.62), p = 0.911 and HR 0.87 (95% CI 0.70-1.68), p = 0.708, respectively). Moreover, IgG concentrations were not associated with peritonitis incidence, nor with the recurrence of peritonitis. Finally, we found no significant difference in dialysate or serum IgG concentrations between patients who remained peritonitis-free (58.0 ± 35.6 mg/L in dialysate, 11.1 ± 4.4 g/L in serum), and those who experienced a peritonitis episode during follow-up (59.5 ± 41.9 mg/L in dialysate, 10.3 ± 4.3 g/L in serum), respectively. Dialysate or serum IgG are not major determinants of local peritoneal defense against peritonitis.

Comparison of Longitudinal Membrane Function in Peritoneal Dialysis Patients According to Dialysis Fluid Biocompatibility

IntroductionPreservation of peritoneal function is essential in long-term peritoneal dialysis. Biocompatible dialysis solutions might prevent or postpone the membrane alteration resulting in ultrafiltration failure and consecutive morbidity and mortality.MethodsWe conducted an observational cohort study in which we made a longitudinal comparison between the course of peritoneal solute and fluid transport during treatment with conventional and biocompatible solutions. Therefore, prospectively collected peritoneal transport data from the yearly standard peritoneal permeability analysis were analyzed in 251 incident patients treated between 1994 and censoring in 2016. Fluid transport included small pore and free water transport. Solute transport was assessed by creatinine mass transfer area coefficient and glucose absorption. Linear mixed models including change point analyses were performed. Interaction with peritonitis was examined.ResultsOne hundred thirty-five patients received conventional and 116 biocompatible solutions. Sixty-seven percent (conventional) and 64% (biocompatible) of these underwent minimally three transport measurements. Initially, biocompatible fluids showed higher small solute transport and lower ultrafiltration than conventional fluids up to 3 years. Thereafter, conventional fluids showed an increase in small solute transport (+2.7 ml/min per year; 95% confidence interval [CI]: 0.9 to 4.5) and a decrease of free water transport (−28.0 ml/min per year; 95% CI: −60.4 to 4.4). These were minor or absent in biocompatible treatment. Peritonitis induced a decrease of transcapillary ultrafiltration after 2 years on dialysis with conventional solutions (−291 ml/min per year; 95% CI: −550 to −32) while this was absent in biocompatible treatment.ConclusionDespite a higher initial solute transport with biocompatible solutions, these have less influence on functional long-term peritoneal alterations than conventional solutions.

The Natural Time Course of Membrane Alterations During Peritoneal Dialysis Is Partly Altered by Peritonitis.

♦ The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis-representing the natural course-and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. ♦ This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990-2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis ("no-peritonitis group") were compared with the results obtained in patients who experienced 1 or more peritonitis episodes ("peritonitis group") during a follow-up of 4 years. ♦ The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the patients who experienced peritonitis (p < 0.01). No difference was observed in the time-course of the effective lymphatic absorption rate. The time-courses of immunoglobulin G and α2-macroglobulin clearances showed a decrease in both patient groups, with a concomitant increase of the restriction coefficient. Those changes were not evidently influenced by peritonitis. The two groups showed a similar decrease in the mesothelial cell mass marker cancer antigen 125 during follow-up. ♦ On top of the natural course of peritoneal function, peritonitis episodes to some extent influence the time-course of small-solute and fluid transport-especially the transport of solute-free water. Those modifications increase the risk for overhydration.

The Mutual Relationship Between Peritonitis and Peritoneal Transport.

♦ Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport. ♦ Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16). ♦ At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport. ♦ Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD.

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.

Longitudinal Analysis of Peritoneal Fluid Transport and Its Determinants in a Cohort of Incident Peritoneal Dialysis Patients

There is a paucity of large longitudinal studies on the time course of peritoneal fluid transport. The aim of the present study was to longitudinally analyze changes in fluid transport and relevant solute transport parameters in patients treated with a conventional peritoneal dialysis (PD) fluid and, to mimic clinical reality, not selected for the presence or absence of ultrafiltration (UF) failure. This prospective single-center cohort study followed 138 consecutive incident PD patients from July 1994 until censoring in August 2004. The design was longitudinal, with repeated measures over time in each patient. Patients had undergone at least 1 and a maximum of 5 annual standard peritoneal permeability analyses (SPAs) using 3.86% glucose dialysate. A linear mixed model was used to analyze the longitudinal data. No differences in patient characteristics were present at baseline in relation to the number of available SPAs. There were also no differences in patient withdrawal during the years of follow-up. A gradual decline in fluid transport, expressed as free water transport (FWT), small-pore fluid transport (SPFT), and transcapillary UF (TCUF), was observed with duration of PD. The decline was mainly attributable to patients who developed UF failure. The time courses for the determinants of fluid transport, such as the reflection coefficient (σ) and the UF coefficient (LpA), were not different. However, they were associated with an increase in the mass transfer area coefficient of creatinine, reflecting the peritoneal vascular surface area. Fluid profiles for FWT and SPFT during a dwell can be explained by current knowledge of the three-pore model. Fluid transport declines with the duration of PD because of an increase in the vascular surface area, leading to a rapid dissipation of glucose as the osmotic agent. The absence of a trend in the time course of osmotic conductance and its constituents-that is, LpA and σ-suggests that, in an unselected population, these parameters are affected only late in the time course of PD.

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.

Peritoneal Albumin and Protein Losses Do Not Predict Outcome in Peritoneal Dialysis Patients

Peritoneal clearance of albumin-unlike the transport of small molecules-is defined by both vascular surface area and size-selective permeability. Few studies have supported a positive correlation between peritoneal albumin loss and mortality. The aim of this study was to investigate whether baseline peritoneal loss and clearance of albumin and other proteins is a risk factor of death in peritoneal dialysis patients. All incident peritoneal dialysis patients in our center during the last 15 years were included. Mass-transfer area coefficient of creatinine and peritoneal clearances of albumin, β₂-microglobulin, α₂-macroglobulin, and immunoglobulin G were calculated during a standard peritoneal permeability analysis. The total amount of albumin loss in the dialysate was also calculated. Overall mortality was studied with an intention-to-treat analysis. Two hundred fifty-seven patients were included. High baseline albumin clearance was associated with fast transport status, the presence of peripheral arterial disease, and a high comorbidity index, whereas C-reactive protein levels did not differ from the patients with low albumin clearance. Age, high comorbidity score, C-reactive protein levels >10 mg/L, and a low serum albumin were associated with mortality. Peritoneal albumin clearances and albumin loss were not associated with death in crude and adjusted analysis. Similarly, peritoneal clearances of immunoglobulin G, α₂-macroglobulin, and β₂-microglobulin were not determinants of survival. Baseline peritoneal albumin and protein clearances are associated with signs of comorbidity, but this does not have a measurable effect on patient survival.

The time course of peritoneal transport parameters in peritoneal dialysis patients who develop encapsulating peritoneal sclerosis

Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). The first aim was to analyse the risk of EPS in patients who had developed ultrafiltration failure (UFF). The second aim was to identify specific peritoneal transport alterations that distinguish patients with UFF from patients who will develop EPS. All patients of this study were treated with PD between July 1995 and December 2008 in the Academic Medical Center, Amsterdam, the Netherlands. Risk analysis: all PD patients who developed UFF after at least 2 years of PD. Peritoneal transport analysis: all patients who had PD for at least 55 months were included: 12 EPS patients, 21 patients with UFF and 26 patients with normal ultrafiltration (UF). The peritoneal function was measured yearly with a standard peritoneal permeability analysis. UFF was defined as net UF < 400 mL after a 4-h dwell with a 3.86% dialysis solution. Risk analysis: Of the 48 UFF patients, 10 eventually developed EPS. Fifty percent of the patients who continued PD for more than 3 years after the establishment of UFF developed EPS. Peritoneal function analysis: No differences were present for the time courses of solute transport and fluid transport between the EPS and the UFF groups. Overall, the EPS and normal UF groups had lower values for the effective lymphatic absorption rate (ELAR) than the UFF group. The risk of EPS increases with continuation of PD while UFF is present. Transport characteristics are similar between EPS patients and UFF patients without this complication. A constantly low ELAR may distinguish the EPS patients from those with UFF only.

Early Diagnostic Markers for Encapsulating Peritoneal Sclerosis: A Case-Control Study

Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term peritoneal dialysis (PD). The aim of this study was to investigate whether dialysate levels of cancer antigen-125 (CA125), K(+), interleukin (IL)-6, and vascular endothelial growth factor (VEGF) are early diagnostic markers of EPS. Therefore, we analyzed the time courses of the above described dialysate markers in EPS patients and controls. Dialysate and serum samples of 11 EPS patients and 31 control patients, all treated with PD for at least 57 months, were longitudinally collected during standard peritoneal permeability analyses. CA125 and IL-6 were measured in dialysate only, K(+) and VEGF were measured in both dialysate and serum. CA125 and IL-6 are expressed as appearance rates (AR). The linear mixed model was used to analyze the time courses. Sensitivity and specificity were calculated based on the results of the last 2 time points. No differences in the time courses of the different markers were present between the groups. For K(+) and VEGF attributed to local production, no differences between the groups were found. However, AR-CA125 was lower during the last 3 years prior to EPS (p < 0.05) and AR-IL-6 tended to be higher 2 years prior to EPS (p = 0.09). The combination of AR-CA125 < 33 U/min and AR-IL-6 > 350 pg/min had a sensitivity of 70% and a specificity of 89% for the development of EPS. Compared to controls, AR-CA125 showed lower values and AR-IL-6 tended to be higher during the last years prior to the diagnosis of EPS. The sensitivity and specificity of the combination of CA125 and IL-6 indicate their potential use for an early diagnosis of EPS.

The relationship between effluent potassium due to cellular release, free water transport and CA125 in peritoneal dialysis patients.

Background. Recently, we found evidence of effluent potassium (K+) additional to diffusion and convection, suggesting cellular release (CR). Its relationship with free water transport (FWT) in stable peritoneal dialysis (PD) patients suggested an effect of hypertonicity of the dialysis solution leading to cell shrinkage. The aim of the present study was to reproduce these findings in groups according to PD duration and to further investigate the role of mesothelial cells in the observed phenomenon.Methods. Standard peritoneal permeability analyses done with 3.86% glucose were analysed cross-sectionally in three different groups: short-term (n = 53) 0–2 years PD treatment; medium-term (n = 24) 2–4 years PD and long-term (n = 26) > 4 years PD.Results. The time courses for FWT and cellular release of K+ (CR-K+) during the dwell were not significantly different among the groups. Cancer antigen (CA) 125 was highest in the short-term group (P ≤ 0.02) and had a strong positive correlation with mass transfer area coefficient of creatinine (MTAC-creatinine) only in the short-term group (r = 0.62, P ≤ 0.01). CA125 had no relationship with either CR-K+ or FWT, except for negative relationships in the short-term group (CR-K+, r = −0.41, P ≤ 0.05; FWT, r = −0.54, P ≤ 0.05).Conclusion. We conclude that the correlation of CA125 and MTAC-creatinine is dependent on PD duration and underlines the in vitro observation that mesothelial cells produce vasoactive substances that may increase the peritoneal surface area. However, CA125 is not directly related to CR-K+ or FWT. Therefore, the relationship between FWT and CR-K+ is likely to reflect hypertonic cell shrinkage, regardless of the duration of PD, and confirms our earlier findings.

Treatment of severe ultrafiltration failure with nonglucose dialysis solutions in patients with and without peritoneal sclerosis

Introduction. Ultrafiltration failure (UFF) in peritoneal dialysis (PD) patients is a reflection of changes in the peritoneal membrane, which can include mesothelial damage, neoangiogenesis, and occasionally, peritoneal fibrosis. These structural changes are probably induced by the use of bioincompatible dialysis solutions. Therefore, we investigated the effects of the treatment with a combination of nonglucose dialysis solutions in patients with severe UFF.Methods. Ten patients with UFF (net ultrafiltration <400 mL/4 h on 3.86% glucose) were treated with a combination of glycerol and icodextrin with or without amino acid-based dialysis solutions for 3 months. Four of them were diagnosed with encapsulating peritoneal sclerosis (PS), proven by peritoneal biopsies. Standard peritoneal permeability analyses (SPA), using 3.86% glucose, were performed, and dialysate CA125 appearance rate (AR-CA125) was analysed at the start, after 6 weeks and after 12 weeks. PS and non-PS patients were compared.Results. One patient underwent transplant after 6 weeks, one was withdrawn from PD because of clinical signs of encapsulating PS before the 3-month period ended. PS patients had been treated with PD for a longer duration than the non-PS patients (102 versus 52 months, P = 0.05), but no differences in baseline transport parameters or AR-CA125 were present. During the study, no differences were observed for transport characteristics when the results of the whole group at 6 and 12 weeks were compared to baseline. For the non-PS patients, however, a significant increase in the transcapillary ultrafiltration rate (from 2.2 mL/min to 2.6 mL/min, P < 0.05) and a decrease in the MTAC creatinine (from 14.3 mL/min to 12.6 mL/min, P < 0.05) were found after 6 weeks of glucose-free treatment. Free-water transport, measured as the maximum dip in the dialysate-to-plasma ratio of sodium and as the transport through the ultrasmall pores in the first minute, tended to improve, but this difference did not reach significance. In addition, the AR-CA125 increased significantly (from 2.8 U/min to 16.1 U/min, P < 0.05). Continued treatment did not reach statistical difference even after 3 months. No changes were observed in the PS patients.Conclusions. In the present study, an improvement of UFF in the non-PS patients was obtained by withdrawal of glucose-based dialysis solutions. The abnormalities in PS patients are probably irreversible. Early withdrawal of glucose-based dialysis solutions or at least a marked reduction in glucose exposure should be considered in UFF patients, but the identification of the patients who would benefit most needs further studies.

Free water transport, small pore transport and the osmotic pressure gradient

Water transport in peritoneal dialysis (PD) patients occurs through the small pores and water channels, the latter allowing free water transport (FWT). The osmotic gradient is known to be one of the major determinants of water transport. The objective of the study was to analyse the relation between each transport route and the osmotic gradient. The 4-h standard peritoneal permeability analyses of 80 stable PD patients were studied. Small pore transport (SPT) was calculated based on the transported amount of sodium. FWT was calculated by subtracting SPT from transcapillary ultrafiltration (TCUF). Water transport rates were determined. The osmotic gradient was calculated. The slope of the relation between FWT rate and osmotic gradient (slope(FWT)), and the elimination constant (K(e)) of the exponential relation between SPT rate and osmotic gradient (K(SPT)) were calculated for every patient. The FWT rate was related to the osmotic gradient (P = 0.001). A similar correlation was also found between the SPT rate and osmotic gradient when fitted exponentially (P = 0.005). The rates of FWT decreased significantly between each time point during the whole dwell. The SPT rates decreased significantly within the first half of the dwell and levelled off thereafter. No correlations were found between the slope(FWT), K(SPT) and PD duration. The slope(FWT) of the relationship between the FWT and the osmotic gradient is an indirect measurement of the amount of functioning water channels. Similarly, the K(SPT) value represents the number of functioning small pores. The absence of a relationship of these parameters with the duration of PD suggests opposing mechanisms, for instance a lower number of functioning pores in combination with an increased vascular surface area. Conclusion. The curves of the relationship between FWR, SPT and OG support the assumption that FWR is much more dependent on the OG than SPT. Non-osmotic determinants are likely to be important in small pore fluid transport.

Does the Biocompatibility of the Peritoneal Dialysis Solution Matter in Assessment of Peritoneal Function?

Peritoneal function tests are performed in peritoneal dialysis (PD) patients to characterize peritoneal membrane status. A low pH/high glucose degradation product (GDP) dialysis solution is used as the test solution. The objective of the present study was to compare a 3.86% glucose, low pH/high GDP dialysis solution (pH 5.5) with a 3.86% glucose, normal pH/low GDP dialysis solution (pH 7.4) in assessments of peritoneal membrane function. Two standard peritoneal permeability analyses (SPA) were performed in 10 stable PD patients within 2 weeks. One SPA was done with the 3.86% low pH/high GDP solution, and the other with the 3.86% normal pH/low GDP solution. The sequence of the two tests was randomized. Fluid transport parameters and glucose absorption were not different between the two groups. No differences were found for the mass transfer area coefficients (MTACs) of low molecular weight solutes calculated over the whole dwell. However, MTAC urea in the first hour of the dwell was higher in the test done with low pH/high GDP dialysate, suggesting more peritoneal vasodilation. No difference was found in protein clearances. Sodium sieving at multiple time points during the dwell was similar with the two solutions. The results obtained with the glucose-containing normal pH/low GDP dialysis solution were similar to those obtained with the glucose-containing low pH/high GDP dialysate in assessments of peritoneal membrane function.

The cellular contribution to effluent potassium and its relation to free water transport during peritoneal dialysis

Aquaporin-1 (AQP-1) dysfunction is one of the valid theories for decreased free water transport (FWT) in long-term peritoneal dialysis (PD) ultrafiltration failure (UFF). We questioned whether apoptosis of peritoneal cells could be reflected in an increased release of cellular (CR) K(+) and explain AQP-1 dysfunction. If so, negative relationships between CR-K(+) and FWT would be expected. Therefore, we analysed CR-K(+) to total peritoneal K(+) removal, for possible relationships with FWT, the duration of PD, the presence of late UFF and effluent cancer antigen (CA) 125. Standard peritoneal permeability analyses done with 3.86% glucose were investigated cross-sectionally in three extreme groups: group I: 19 patients <1 year on PD; group II: 20 patients >4 years on PD without UFF; group III: 19 patients >4 years on PD with UFF. Group III had the lowest values of FWT and CR-K(+) (P < 0.01). CR-K(+) had a positive correlation with FWT in groups I and II, but not in group III. These correlations were also present using much simpler methodologies: replacement of CR-K(+) by mass transfer area coefficient (MTAC)-K(+)/MTAC-creatinine ratio or dialysate over plasma (D/P)-K(+)/D/P-creatinine ratio and replacement of FWT by Na(+)-sieving. No relationship with CA125 was present. This study shows that other than diffusive and convectional, K(+) transport is not excluded in patients treated with conventional glucose-based PD solutions. We found evidence for release of K(+) from cells. In general, CR-K(+) was related to parameters of FWT, except for long-term patients with UFF. This suggests glucose-induced hypertonic cell shrinkage as a basic physiological phenomenon during PD. The absence of this relationship in long-term PD patients with UFF either suggests a reduction or inhibition of K(+)-channels and may be due to another mechanism than AQP-1 dysfunction. Most likely, CR-K(+) in UFF does not reflect apoptosis. However, the D/P-K(+)/D/P-creatinine ratio may be useful in detecting peritoneal changes.

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.

Analysis of fluid transport pathways and their determinants in peritoneal dialysis patients with ultrafiltration failure

Ultrafiltration failure (UFF) is a serious complication of peritoneal dialysis (PD). The aim of the study was to analyze changes in water transport and their determinants in UFF patients over the time on PD. Standard peritoneal permeability analyses of 50 stable PD patients with UFF were analyzed. Fluid transport through small pores (SPT), free water transport (FWT) at 60 min, their contributions on total ultrafiltration (SPTC and FWTC), and their determinants were assessed. Patients were divided in Group I (UFF) treated for less than 24 months, Group II treated 24-60 months, and Group III treated for more than 60 months. Group I (UFF) was compared with Group I (non-UFF) matched for the duration of PD treatment and age. Transcapillary ultrafiltration (TCUF), SPT, FWT, and FWTC were significantly lower in Group III when compared to the other UFF groups. In this group also, negative relationship was present between FWT, the ultrafiltration coefficient LpA, and osmotic conductance to glucose on one hand and PD duration on the other. FWT was positively related to osmotic conductance to glucose in all groups. Group I (UFF) showed significantly higher solute transport, effective lymphatic absorption rate, lower TCUF, and lower FWT than Group I (non-UFF). The patterns of UFF in PD patients are dependent on the duration of treatment.

Modeling of Icodextrin in PD Adequest® 2.0

To validate the use of a modified three-pore model for predicting fluid transport during long dwell exchanges that use a 7.5% icodextrin solution. A nonrandomized, single group, repeated measures study. Ten peritoneal dialysis patients underwent a single 8-hour exchange of a 7.5% icodextrin solution. All patients were naive to icodextrin. A modified three-pore model was used to model solute and fluid transport during each 8-hour exchange. Concordance correlation coefficients were used to estimate the level of agreement between modeled and measured values of net ultrafiltration (UF) and intraperitoneal volume. Each patient underwent a modified 8-hour standard peritoneal permeability analysis using a 2-L 7.5% icodextrin exchange. Dextran 70 was added to the icodextrin solution as volume marker to estimate fluid transport kinetics. Transcapillary UF, fluid absorption, and intraperitoneal volumes were assessed via the volume marker at 0, 5, 15, 30, 60, 120, 240, 300, 360, 420, and 480 minutes. There was strong agreement (concordance correlation = 0.9856) between net UF as measured by the volume marker data and net UF as modeled using the modified three-pore model implemented in PD Adequest (Baxter Healthcare, Deerfield, Illinois, USA). Net UF and intraperitoneal volumes for long dwell exchanges using a 7.5% icodextrin solution can be accurately modeled with a modified three-pore model. Steady state icodextrin plasma levels are needed to accurately predict net UF for chronic users of icodextrin.

The contribution of free water transport and small pore transport to the total fluid removal in peritoneal dialysis

Water transport in peritoneal dialysis (PD) patients is across the small pores and water channels, the latter allowing free water transport. The objective of the study was to investigate the contribution of each transport route on transcapillary ultrafiltration (TCUF). Standard peritoneal permeability analyses of 80 stable PD patients were analyzed. Twenty-nine patients were followed longitudinally. Fluid transport through small pores (SPT) was assessed by the amount of transported sodium. Free water transport (FWT) was calculated by subtracting SPT from TCUF. The contribution of FWT and SPT to the TCUF and water transport rates at any time point was computed. The ultrafiltered volume due to SPT increased gradually during the dwell, while FWT reached its maximum around 3 hours. The rate of FWT decreased continuously during the dwell. SPT decreased during the initial 2 hours and remained stable thereafter. At 60 minutes, the SPT (P < 0.05) and its contribution (P < 0.05) were positively related to the MTAC(creat). The contribution of FWT after 1 hour, but not the absolute amount, showed an inverse relationship. Peritoneal solute transport parameters (P < 0.01) and the contribution of SPT (P= 0.08), but none of the other fluid parameters showed a U-shape with the lowest values in the second year of PD (P < 0.01). The dwell courses of water transport suggest that the activity of water channels is dependent and limited by the crystalloid osmotic pressure gradient, while other determinants are important in SPT. The time-course of SPT paralleled that of peritoneal solute transport parameters.

The Difference in Causes of Early and Late Ultrafiltration Failure in Peritoneal Dialysis

Ultrafiltration failure (UFF) is a major complication of peritoneal dialysis. Although it seems associated with long-term treatment, it can also occur in recently started patients. To identify the causes of this complication in patients with early and late UFF we studied a group of 48 patients. Patients were classified as early if they had been treated for less than 2 years and as late if they had been treated for more than 4 years. The patients were studied using a standard peritoneal permeability analysis. They all had a net ultrafiltration of less than 400 mL after a 4-hour dwell with 3.86% glucose. As possible causes for UFF, the solute transport parameters dialysate-to-plasma ratio (D/P) and mass transfer area coefficient of creatinine were compared, as well as the effective lymphatic absorption rate (ELAR) and the maximum dip in D/P sodium as an assessment of osmotic conductance to glucose. 25 short-term patients were compared with 23 long-term patients. Both groups showed an equal distribution of high small solute transport rates as a cause of UFF. The chi-square test showed that a high ELAR was a more frequent cause in early UFF compared to late UFF. However, a decreased osmotic conductance to glucose was significantly more often observed in late UFF. Some patients showed more than one cause of the complication. This study has shown that UFF in long-term patients is often caused by a decreased osmotic conductance to glucose, most likely caused by a dysfunction of peritoneal water channels in combination with increased peritoneal surface area. In short-term patients, aquaporin dysfunction is rare, but a high ELAR was a very important factor in the occurrence of UFF.