Transcapillary Ultrafiltration Research Articles

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.

Long Peritoneal Dialysis Dwells With Icodextrin: Kinetics of Transperitoneal Fluid and Polyglucose Transport.

Background and objective: During peritoneal dialysis (PD), the period of effective net peritoneal ultrafiltration during long dwells can be extended by using the colloidal osmotic agent icodextrin but there are few detailed studies on ultrafiltration with icodextrin solution exceeding 12 h. We analyzed kinetics of peritoneal ultrafiltration in relation to icodextrin and its metabolites for 16-h dwells with icodextrin.Design, setting, participants, and measurements: In 20 clinically stable patients (mean age 54 years; 8 women; mean preceding time on PD 26 months), intraperitoneal dialysate volume (VD) was estimated from dilution of 125I-human serum albumin during 16-h dwell studies with icodextrin 7.5% solution. Sodium was measured in dialysate and plasma. In 11 patients, fractional absorption of icodextrin from dialysate, dialysate, and plasma amylase and high and low (Mw <2 kDa) Mw icodextrin fractions were analyzed.Results: Average VD increased linearly with no difference between transport types. At 16 h, the cumulative net ultrafiltration was 729 ± 337 ml (range −18 to 1,360 ml) and negative in only one patient. Average transcapillary ultrafiltration rate was 1.40 ± 0.36 ml/min, and peritoneal fluid absorption rate was 0.68 ± 0.38 ml/min. During 16 h, 41% of the initial mass of icodextrin was absorbed. Plasma sodium decreased from 138.7 ± 2.4 to 136.5 ± 3.0 mmol/L (p < 0.05). Dialysate glucose G2–G7 oligomers increased due to increase of G2–G4 metabolites while G6–G7 metabolites and higher Mw icodextrin fractions decreased. In plasma maltose and maltotriose (G2–G3 metabolites) increased while higher Mw icodextrin oligomers were almost undetectable. Dialysate amylase increased while plasma amylase decreased.Conclusions: Icodextrin resulted in linear increase of VD with sustained net UF lasting 16 h and with no significant difference between peritoneal transport types. In plasma, sodium and amylase declined, G2–G3 increased whereas larger icodextrin fractions were not detectable. In dialysate, icodextrin mass declined due to decrease of high Mw icodextrin fractions while low Mw metabolites, especially G2–G3, increased. The ability of icodextrin to provide sustained UF during very long dwells – which is usually not possible with glucose-based solutions – is especially important in anuric patients and in patients with fast peritoneal transport.

Peritoneal vasculopathy in the pathophysiology of long-term ultrafiltration failure: A hypothesis based on clinical observations .

Ultrafiltration failure in long-term peritoneal dialysis patients is a well-known and important, but poorly-explained complication of the treatment. Transcapillary ultrafiltration consists mainly of small-pore fluid transport and partly of free-water transport. The former is to a large extent dependent on the hydrostatic pressure gradient and on the number of perfused peritoneal microvessels. Free-water transport depends mainly on the crystalloid osmotic gradient. A longitudinal analysis of peritoneal transport has shown a dramatic decrease of net ultrafiltration and small-pore fluid transport after 4years of peritoneal dialysis. It will be argued that in contrast to common belief, a decrease of osmotically induced water transport cannot be the major contributor to long-term ultrafiltration failure. By exclusion of potential alternatives, the presence of vasculopathy in the peritoneal microcirculation is the most likely explanation. The resulting narrowing of vascular lumina will decrease the hydrostatic pressure gradient and thereby small-pore fluid transport and net ultrafiltration. Deposition of advanced glycosylation end products in peritoneal vessels may be important in the development of vasculopathy. This hypothesis is supported by morphological and functional results of dialysis with "biocompatible" solutions. .

Ultrafiltration Failure Is a Reflection of Peritoneal Alterations in Patients Treated With Peritoneal Dialysis.

Ultrafiltration (UF) failure is a common and important complication of peritoneal dialysis (PD), especially in long-term patients without residual urine production, because it often causes overhydration, which is an important cause of death in this population. The current review provides an overview of the pathways of peritoneal fluid transport, followed by the mechanisms and causes of UF failure. The egression of circulating fluid to the tissue compartment and its subsequent re-uptake by the colloid osmotic pressure are markedly influenced by PD, because the dialysis solutions contain glucose as a low molecular weight agent causing removal of fluid from the circulation by crystalloid osmosis. Pores involved in transcapillary UF consist of inter-endothelial small pores and the intra-endothelial water channel aquaporin-1. The former allows transport of plasma fluid with dissolved low molecular weight solutes and accounts for 60% of the filtered volume, the latter transports 40% as pure water. This free water transport (FWT) is driven by the crystalloid pressure gradient, while small pore fluid transport (SPFT) is dependent on both hydrostatic and crystalloid osmotic pressure. The number of perfused peritoneal microvessels as assessed by small solute transport parameters, is differently associated with UF: a positive relationship is present with SPFT, but a negative one with FWT, because the effect of more vessels is counteracted by a faster disappearance rate of glucose. Ultrafiltration failure can be present shortly after the start of PD, for instance due to mesothelial-to-mesenchymal transition. Late UF failure develops in 21% of long-term patients. Both FWT and SPFT can be affected. Patients with encapsulating peritoneal sclerosis have severely impaired FWT, probably due to interference of interstitial collagen-1 with the crystalloid osmotic gradient. This mechanism may also apply to other patients with reduced FWT. Those with mainly impaired SPFT likely have a reduced hydrostatic filtration pressure due to vasculopathy. Deposition of advanced glycosylation end products is probably important in the development of this vasculopathy. It can be concluded that long-term UF failure may affect both SPFT and FWT. Vasculopathy is important in the former, interstitial fibrosis in the latter. Measurements of peritoneal transport function should include separate assessments of small pore-and FWT.

Transport of neutral IgG2 versus anionic IgG4 in PD: implications on the electrokinetic model

BackgroundIt is debated whether transperitoneal membrane transport of larger (charged) molecules in peritoneal dialysis can be partially governed by the electrokinetic model. In this model, it is postulated that streaming potentials are generated across the capillary wall by forced filtration of an ionic solution, for example transcapillary ultrafiltration induced by osmotic forces as in peritoneal dialysis. We investigated the presence of streaming potentials in the process of transperitoneal transport in Peritoneal Dialysis (PD) patients by measuring ratios of dialysate concentrations of IgG2 (neutral) and IgG4 (negative), both 150kD, under different conditions of transcapillary ultrafiltration.MethodsAdult PD patients randomly got two consecutive dwells of 120 min each, with either 2 L Physioneal 1.36% or 3.86% glucose dialysis fluid (Baxter, USA) as their first dwell. A blood sample was taken at the test start, and dialysate samples were taken at 5, 15, 30, 60 and 120 min. IgG2 and IgG4 concentrations were measured (ELISA) and ratios calculated.ResultsIn 10 patients (65 ± 17 years, 20 ± 17 months on dialysis), drained volume after 120 min was different between the 1.36% (1950 [1910; 2020] mL) and 3.86% (2540 [2380; 2800] mL) glucose dwells (P = 0.007). At none of the time points and irrespective of glucose concentration, a significant difference was found between the IgG2/IgG4 ratios at any time point.ConclusionOur data failed to demonstrate a difference in the transport ratios of two macromolecules with same molecular weight but different charge, as would be expected by the electrokinetic model, and this despite sufficient differences in transcapillary ultrafiltration.Clinical trial registryBelgian Registration Number B670201523397 (20/1/2015); prospective randomized trial.

Mechanisms of Crystalloid versus Colloid Osmosis across the Peritoneal Membrane.

Background Osmosis drives transcapillary ultrafiltration and water removal in patients treated with peritoneal dialysis. Crystalloid osmosis, typically induced by glucose, relies on dialysate tonicity and occurs through endothelial aquaporin-1 water channels and interendothelial clefts. In contrast, the mechanisms mediating water flow driven by colloidal agents, such as icodextrin, and combinations of osmotic agents have not been evaluated.Methods We used experimental models of peritoneal dialysis in mouse and biophysical studies combined with mathematical modeling to evaluate the mechanisms of colloid versus crystalloid osmosis across the peritoneal membrane and to investigate the pathways mediating water flow generated by the glucose polymer icodextrin.ResultsIn silico modeling and in vivo studies showed that deletion of aquaporin-1 did not influence osmotic water transport induced by icodextrin but did affect that induced by crystalloid agents. Water flow induced by icodextrin was dependent upon the presence of large, colloidal fractions, with a reflection coefficient close to unity, a low diffusion capacity, and a minimal effect on dialysate osmolality. Combining crystalloid and colloid osmotic agents in the same dialysis solution strikingly enhanced water and sodium transport across the peritoneal membrane, improving ultrafiltration efficiency over that obtained with either type of agent alone.Conclusions These data cast light on the molecular mechanisms involved in colloid versus crystalloid osmosis and characterize novel osmotic agents. Dialysis solutions combining crystalloid and colloid particles may help restore fluid balance in patients treated with peritoneal dialysis.

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.

Estimation of Residual Peritoneal Volume Using Technetium-99m Sulfur Colloid Scintigraphy.

Residual peritoneal volume (RPV) may contribute in the development of ultrafiltration failure in patients with normal transcapillary ultrafiltration. The aim of this study was to estimate the RPV using intraperitoneal technetium-99m Sulfur Colloid (Tc). Twenty patients on peritoneal dialysis were studied. RPV was estimated by: 1) intraperitoneal instillation of Tc (RPV-Tc) and 2) classic Twardowski calculations using endogenous solutes, such as urea (RPV-u), creatinine (RPV-cr), and albumin (RPV-alb). Each method's reproducibility was assessed in a subgroup of patients in two consecutive measurements 48 h apart. Both methods displayed reproducibility (r = 0.93, p = 0.001 for RPVTc and r = 0.90, p = 0.001 for RPV-alb) between days 1 and 2, respectively. We found a statistically significant difference between RPV-Tc and RPV-cr measurements (347.3 ± 116.7 vs. 450.0 ± 67.8 ml; p =0.001) and RPV-u (515.5 ± 49.4 ml; p < 0.001), but not with RPV-alb (400.1 ± 88.2 ml; p = 0.308). A good correlation was observed only between RPV-Tc and RPV-alb (p < 0.001). The Tc method can estimate the RPV as efficiently as the high molecular weight endogenous solute measurement method. It can also provide an imaging estimate of the intraperitoneal distribution of RPV.

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.

Time Course of Peritoneal Function in Automated and Continuous Peritoneal Dialysis

In automated peritoneal dialysis (APD), a patient's peritoneal membrane is more intensively exposed to fresh dialysate than it is in continuous ambulatory peritoneal dialysis (CAPD). Our aim was to study, in incident peritoneal dialysis (PD) patients, the influence of APD-compared with that of CAPD-on peritoneal transport over 4 years. Patients were included if at least 2 annual standard permeability analyses (SPAs) performed with 3.86% glucose were available while the patient was using the same modality with which they had started PD (APD or CAPD). Patients were followed until their first modality switch. Differences in the pattern of SPA outcomes over time were tested using repeated-measures models adjusted for age, sex, comorbidity, primary kidney disease, and year of PD start. The 59 CAPD patients enrolled were older than the 47 APD patients enrolled (mean age: 58 ± 14 years vs 49 ± 14 years; p < 0.01), and they had started PD earlier (mean start year: 2000 vs 2002). Over time, no differences in solute (p > 0.19) or fluid transport (p > 0.13) were observed. Similarly, free water transport (p = 0.43) and small-pore transport (p = 0.31) were not different between the modalities. Over time, patients on APD showed a faster decline in effective lymphatic absorption rate (ELAR: p = 0.02) and in transcapillary ultrafiltration (TCUF: p = 0.07, adjusted p = 0.05). Further adjustment did not change the results. Compared with patients starting on CAPD, those starting on APD experienced a faster decline in ELAR and TCUF. Other transport parameters were not different over time between the groups.

Free water transport in children on peritoneal dialysis is higher with more biocompatible dialysis solutions, higher with older age and declines with time

Water transport in peritoneal dialysis occurs through small pores and aquaporins. Free water transport (FWT) occurs through aquaporins only and gives a reflection of peritoneal aquaporin function. In this study, FWT in children was calculated for the first time in different settings. A prospective cohort study was performed; 87 peritoneal equilibrium tests (PETs) were analysed in 65 patients. Three subgroups were analysed: patients with their first PET; patients in their second year on dialysis; patients in their third year on dialysis or thereafter. Patients using 3.86% glucose solution with low pH/high glucose degradation products (GDP) were compared to patients using 3.86% glucose solution with neutral pH/low GDP. Sixteen patients using neutral pH/low GDP solution were followed longitudinally. FWT was calculated using the dialysate/plasma ratio of sodium. The proportional contribution of FWT was significantly higher in patients using dialysis solution with neutral pH/low GDP solution compared to patients using solutions with low pH/high GDP (50 versus 40%). Transcapillary ultrafiltration (TCUF) showed the same trend but was not statistically significant. Total FWT was higher as well. Higher FWT was observed with older age. In the longitudinal group, TCUF and water transport through small pores declined, while FWT remained stable in the first 1.5 years. The contribution of FWT increased in this period (48-61%), then slowly declined again to baseline level during the third year. Total FWT and relative contribution of FWT were significantly higher with neutral pH/low GDP solution. This can reflect a better preservation of aquaporins. The decline in the contribution of FWT in long-term dialysis could hypothetically implicate aquaporin dysfunction or different trafficking of aquaporins.

Water and Solute Transport through Different Types of Pores in Peritoneal Membrane in Capd Patients with Ultrafiltration Failure

Free water transport, an estimate of aquaporin function, was evaluated in 7 continuous ambulatory peritoneal dialysis (CAPD) patients with permanent ultrafiltration failure. In 3 patients, peritoneal transport was studied also before the onset of ultrafiltration failure. Transcapillary ultrafiltration and fluid absorption rates were assessed using radiolabeled albumin, and free water transport by kinetics of sodium concentration in dialysis fluid. Diffusive and convective transport rates of small solutes were estimated using the modified Babb-Randerson-Farrell model. Increased diffusive transport of small solutes was found in 5 patients and increased peritoneal fluid absorption in 2 patients. The 3-pore model was fitted to these data. Overall, hydraulic conductivity and the fractional contributions of aquaporins to hydraulic conductivity were either decreased or normal. We conclude that the quantitative role of aquaporins in overall fluid transport may vary substantially in normal patients as well in patients with ultrafiltration failure.

Clinical effects of icodextrin in peritoneal dialysis.

Objective. This study reviews the relevant publications on the clinical effects of icodextrin in peritoneal dialysis (PD).Design. The study provides a systematic review of the literature (MEDLINE search with icodextrin as the keyword).Results. Icodextrin induces sustained transcapillary ultrafiltration during long dwell periods. It also stimulates increased removal of sodium by the peritoneal membrane, reduction of extracellular water (ECW) and total body water (TBW). Effects of icodextrin on blood pressure control and residual renal function are discrepant. Icodextrin induces a reduction in the formation of advanced glycation end-products, while the longitudinal changes in the peritoneal membrane transport are less prominent.Conclusions. Use of icodextrin in PD improves the sodium and fluid balance. Icodextrin is potentially more biocompatible, when compared with the conventional glucose solutions. The side effects are rare.

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.

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.

No Significant Differences in Peritoneal Fluid Handling in Children Using pH-Neutral or Acidic Solutions

Differences in peritoneal fluid handling in the acute setting can be expected if children are converted to pH-neutral dialysis solutions because conventional acidic solutions exert toxic effects on peritoneal mesothelial cells and microcirculation. Peritoneal fluid kinetics was therefore investigated with both types of solutions in a group of children. Peritoneal equilibration tests (PETs) were performed in 12 patients [mean age 70 months, mean time on peritoneal dialysis (PD) 18 months] using a pH-neutral PD fluid (Physioneal 3.86%; Baxter Ltd, Castlebar, Ireland) and dextran 70 as a volume marker. The results of these PETs were compared to those of a historic group of 12 children (mean age 75 months, mean time on PD 17 months). Pediatric dialysis unit in a tertiary institute. Stable pediatric PD patients. Transcapillary ultrafiltration (TCUF) and marker clearance, dialysate-to-plasma (D/P) ratios for urea and creatinine, and D(t)/D(0) ratio for glucose. TCUF and lymphatic absorption were not different between the two groups. There was also no significant difference in small solute clearance measured by D/P ratio for urea and creatinine and D(t)/D(0) ratio for glucose. Peritoneal fluid kinetics is not significantly altered if pH-neutral dialysis solutions are applied compared to acidic solutions. An altered TCUF, as is hypothetically possible using an acidic solution, was not established.

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.