Transcapillary Ultrafiltration Rate Research Articles

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.

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 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.

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.

Peritoneal Transport Characteristics with Glucose Polymer–Based Dialysis Fluid in Children

Scarce data are available on the use of glucose polymer-based dialysate in children. The effects of glucose polymer-based dialysate on peritoneal fluid kinetics and solute transport were studied in pediatric patients who were on chronic peritoneal dialysis, and a comparison was made with previously published results in adult patients. In nine children, two peritoneal equilibration tests were performed using 3.86% glucose and 7.5% icodextrin as a test solution. Dextran 70 was added as a volume marker to calculate fluid kinetics. Serum and dialysate samples were taken for determination of urea, creatinine, and sodium. After calculation of the initial transcapillary ultrafiltration (TCUF) rate, it was possible to calculate the contribution of aquaporin-mediated (AQP-mediated) water transport to ultrafiltration for icodextrin and 3.86% glucose and the part of L(p)S (the product of the peritoneal surface area and the hydraulic permeability) caused by AQP. In children, the transport parameters were similar for the two solutions, except for TCUF, which was lower for icodextrin (0.9 ml/min per 1.73 m(2)) as compared with 3.86% glucose (4 ml/min per 1.73 m(2)). Transport parameters were similar in children and adults for glucose, but with icodextrin, TCUF and marker clearance were significantly lower in children. AQP-mediated water flow was 83 versus 50% with glucose (child versus adult; P < 0.01) and 18 versus 7% with icodextrin (P < 0.01). Data indicate that transport parameters in children using icodextrin are similar to glucose except for TCUF. Differences are explained by the absence of crystalloid osmosis and that TCUF was determined after a 4-h dwell. Comparison of transport parameters and peritoneal membrane characteristics between children and adults reveal that there seem to be differences in the amount and functionality of AQP. However, there are no differences in clinical efficacy of this transport pathway because the absolute flow through the AQP is identical in both groups using 3.86% glucose.

Profiling of peritoneal ultrafiltration

The historical course of peritoneal dialysis can be charOVERVIEW OF ULTRAFILTRATION acterized by successive phases of development: the first PHYSIOLOGY phase after the introduction of continuous ambulatory It is important at the outset to review the balance of peritoneal dialysis (CAPD) was focused on establishing opposing forces governing peritoneal ultrafiltration in the therapy, addressing pressing technological needs in PD. These can be readily illustrated from the early work connectology and introduction of automation [1–8]. The of Mactier et al [17] represented in Figure 1. They evalusecond phase tackled controversial issues and ultimately ated ultrafiltration (UF) kinetics observed with the use led to the resolution of two contentious aspects: the vindiof 2.5% dextrose solution in CAPD patients with normal and high peritoneal transport patterns. The changes in cation of peritoneal dialysis as a long-term therapy with intraperitoneal volume are characterized by a biphasic patient outcomes equivalent to those of hemodialysis behavior: in the initial phase this is dominated by trans[9–12], and the proper determination of the relative imcapillary ultrafiltration, which is driven principally by the portance of small solute clearance by a definitive rancrystalloid osmotic gradient generated by glucose but is domized controlled trial [13] and cumulative observagoverned also by the relatively constant hydrostatic and tional explorations [reviewed in 13]. The present third oncotic pressure gradients (the so-called ‘Starling forces’) phase of the history of the therapy can be defined as [18]. As transcapillary ultrafiltration rate exceeds lymthat of focus on fluid balance and cardiovascular outphatic and tissue absorption, intraperitoneal volume incomes. This phase was heralded by the landmark work creases [17]. The decline in glucose concentration, howof the International Society of Peritoneal Dialysis ad hoc ever, occurs precipitously resulting in a decrease in the Committee of Ultrafiltration Management in Peritoneal transcapillary ultrafiltration rate. As long as transcapilDialysis [14, 15], which corrected the critical absence lary ultrafiltration exceeds lymphatic absorption, the of fluid management issues from dialysis management peritoneum is operating under a fluid transport disequiguidelines issued by various committees [16]. The work librium favoring positive net ultrafiltration. When the of the committee highlighted not only the importance transcapillary ultrafiltration rate declines to a value equal of the issue of fluid management, but also the limitations to the lymphatic flow rate, a state of equilibrium in fluid inherent in diagnostic evaluations of peritoneal ultrafiltransport obtains and no increase in intraperitoneal voltration [15]. One of the critical recommendations of the ume occurs. This is the point at which peak intraperitocommittee was the adoption of a variant of the peritoneal neal volume is reached. Peak UF volume is observed equilibration test (PET) utilizing a higher glucose conbefore osmotic equilibrium between serum and dialysate centration (4.25% dextrose/3.86% glucose) for the evaluis reached and occurs when the rate of net transcapillary ation of ultrafiltration failure [15]. This was based on the UF slows to equal that of lymphatic reabsorption [17]. recognition of the inadequacy of the standard 2.5/2.27% Thereafter, the rate of lymphatic reabsorption exceeds test to discriminate between true ultrafiltration failure that for net transcapillary UF, resulting in reduced intraand normal inter-individual variations. The aim of the peritoneal volume. present article is to pursue further the evaluation of The difference between the declining transcapillary the value of the standard PET in profiling peritoneal ultrafiltration rate and the constant lymphatic tissue absorption eventually leads to a new state of fluid transport ultrafiltration, and to offer a profiling model based on disequilibrium dominated by net fluid absorption and more extensive clinical data and mathematical modeling. negative net ultrafiltration. This characterizes the second and final phase of changes in intraperitoneal volume: a linear and steady decline [17, 18].

Peritoneal Transport Characteristics with Glycerol-Based Dialysate in Peritoneal Dialysis

Glycerol is a low molecular weight solute (MW 92 D) that can be used as an osmotic agent in continuous ambulatory peritoneal dialysis (CAPD). Due to its low molecular weight, the osmotic gradient disappears rapidly. Despite the higher osmolality at the beginning of a dwell, ultrafiltration has been found to be lower for glycerol compared to glucose (MW 180 D) when equimolar concentrations are used. Previous studies have shown glycerol to be safe for long-term use, but some discrepancies have been reported in small solute transport and protein loss. To assess permeability characteristics for a 1.4% glycerol dialysis solution compared to 1.36% glucose. Two standardized peritoneal permeability analyses (SPA), one using 1.4% glycerol and the other using 1.36% glucose, in random order, were performed within a span of 2 weeks in 10 stable CAPD patients. The length of the study dwell was 4 hours. Fluid kinetics and solute transport were calculated and signs of cell damage were compared for the two solutions. Peritoneal dialysis unit in the Academic Medical Center, Amsterdam. Median values for the 1.4% glycerol SPA were as follows: net ultrafiltration 251 mL, which was higher than that for 1.36% glucose (12 mL, p < 0.01); transcapillary ultrafiltration rate 2.12 mL/min, which was higher than that for glucose (1.52 mL/min, p = 0.01); and effective lymphatic absorption rate 1.01 mL/min, which was not different from the glucose-based solution. Calculation of peritoneal reflection coefficients for glycerol and glucose showed lower values for glycerol compared to glucose (0.03 vs 0.04, calculated with both the convection and the diffusion models). A marked dip in dialysate-to-plasma ratio for sodium was seen in the 1.4% glycerol exchange, suggesting uncoupled water transport through water channels. Mass transfer area coefficients for urea, creatinine, and urate were similar for both solutions. Also, clearances of the macromolecules beta2-microglobulin, albumin, IgG, and alpha2-macroglobulin were not different for the two osmotic agents. The median absorption was higher for glycerol, 71% compared to 49% for glucose (p < 0.01), as could be expected from the lower molecular weight. The use of a 1.4% glycerol solution during a 4-hour dwell caused a small but significant median rise in plasma glycerol, from 0.22 mmol/L to 0.45 mmol/L (p = 0.02). Dialysate cancer antigen 125 and lactate dehydrogenase (LDH) concentrations during the dwell were not different for both solutions. These findings show that glycerol is an effective osmotic agent that can replace glucose in short dwells and show no acute mesothelial damage. The higher net ultrafiltration obtained with 1.4% glycerol can be explained by the higher initial net osmotic pressure gradient. This was seen especially in the first hour of the dwell. Thereafter, the osmotic gradient diminished as a result of absorption. The dip in dialysate-to-plasma ratio for sodium seen in the glycerol dwell can also be explained by this high initial osmotic pressure gradient, implying that the effect of glycerol as an osmotic agent is more dependent on intact water channels than is glucose.

High peritoneal residual volume decreases the efficiency of peritoneal dialysis

Wide variation in peritoneal residual volume (PRV) is a common clinical observation. High PRV has been used in both continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis to minimize the time of a dry peritoneal cavity and to achieve better dialysis. However, the impact of PRV on peritoneal transport is not well established. In this study, we investigated the effect of PRV on peritoneal transport characteristics. Peritoneal effluents were collected in 32 male Sprague-Dawley rats after a five-hour dwell with 1.36% glucose solution. Forty-eight hours later, a four hour dwell using 25 ml of 3.86% glucose solution and frequent dialysate and blood sampling was done in each rat with 125I-albumin as a volume marker. Before the infusion of the 3.86% glucose solution, 0 (control), 3, 6, or 12 ml (8 rats in each group) of autologous effluent (serving as PRV) was infused to the peritoneal cavity. After subtracting the PRV, the net ultrafiltration was significantly lower in the PRV groups as compared with the control group: 13.4 +/- 0.5, 12.0 +/- 1.0, 11.7 +/- 1.7, and 8.9 +/- 0.4 ml for 0, 3, 6, and 12 ml PRV groups, respectively (P < 0.001). The lower net ultrafiltration associated with higher PRV was due to (a) a significantly lower transcapillary ultrafiltration rate (Qu) caused by a lower osmotic gradient, and (b) a significantly higher peritoneal fluid absorption rate (KE) caused by an increased intraperitoneal hydrostatic pressure. No significant differences were found in the diffusive mass transport coefficient for small solutes (glucose, urea, sodium, and potassium) and total protein, although the dialysate over plasma concentration ratios values were higher in the high-PRV groups. The sodium removal was significantly lower in the PRV groups as compared with the control group (P < 0.01). Our results suggest that a high PRV may decrease net ultrafiltration through decreasing the Qu, which is caused by a decreased dialysate osmolality, and increasing the KE caused by an increased intraperitoneal hydrostatic pressure. The high volume of PRV also decreased the solute diffusion gradient and decreased peritoneal small solute clearances, particularly for sodium. Therefore, a high PRV may compromise the efficiency of dialysis with a glucose solution.

Hyaluronan decreases peritoneal fluid absorption: Effect of molecular weight and concentration of hyaluronan

We have recently shown that the addition of hyaluronan to peritoneal dialysis solution could decrease the peritoneal fluid absorption rate, possibly through decreasing peritoneal tissue hydraulic conductivity. The physical-chemical properties of hyaluronan were found to be both molecular weight and concentration dependent. In this study, we investigated the effects of different molecular weight as well as different concentrations of hyaluronan on the peritoneal fluid kinetics. A four-hour dwell study was performed in 48 male Sprague-Dawley rats (6 rats in each group) with 131I albumin (RISA) as an intraperitoneal volume marker. Each rat was intraperitoneally injected with 25 ml of 1.36% glucose dialysate alone (control) or with 0.01% hyaluronan (HA) with different molecular weights [85,000 (HA85K group), 280,000 (HA280K group), 500,000 (HA500K group), and 4,000,000 (HA4M group) molecular wt] or with a different concentrations of hyaluronan [(molecular wt 500,000); 0.01% (0.01% HA group), 0.05% (0.05% HA group), 0.1% (0.1% HA group), and 0.5% (0.5% HA group) hyaluronan]. The peritoneal fluid absorption rate (as assessed by the RISA elimination rate, KE) was significantly decreased in the HA500K and H4M groups as well as in all the different concentration groups (with molecular wt 500,000) as compared with the control group, resulting in significantly higher net fluid removal in these groups (except for the H4M group) as compared with the control group. In the 0.5% HA group (but not in the other hyaluronan groups), the direct lymphatic absorption (KEB) was also significantly decreased. The transcapillary ultrafiltration rate (Qu) was significantly lower in the HA4M group as compared with the control group but significantly higher in the 0.05% HA (and tended to be higher in the 0.1% HA group) as compared with the other groups. No difference in Qu was found between the 0.5% HA group as compared with the control group, despite a more marked decrease in KE in this group as compared with the H4M group. There were no significant differences in KE, Qu, and net fluid removal between the HA85K and HA280K groups and the control group. Our results suggest that (a) the addition of hyaluronan to dialysate could decrease peritoneal fluid absorption and thus increase the net ultrafiltration; this effect appears to be both size dependent and concentration dependent. (b) High molecular weight fraction of hyaluronan may also decrease the transcapillary Qu by decreasing tissue hydraulic conductivity. (c) A higher concentration of hyaluronan in dialysate resulted in a more marked decrease in peritoneal fluid absorption (absorption to peritoneal tissues as well as direct lymphatic absorption), possibly through both decreasing tissue hydraulic conductivity and increasing fluid viscosity. (d) Decreasing tissue hydraulic conductivity by adding a high concentration of hyaluronan to dialysate does not decrease the transcapillary ultrafiltration, possibly because the osmotic effect of hyaluronan may counterbalance the decrease in transcapillary ultrafiltration because of the decrease in tissue hydraulic conductivity.

Intraperitoneal Addition of Hyaluronan Improves Peritoneal Dialysis Efficiency

It has been shown that hyaluronan (HA) can decrease peritoneal fluid absorption. It is not known, however, how various molecular weights and various concentrations of hyaluronan affect peritoneal fluid absorption rate. A study of 4-hour dwells, with frequent dialysate and blood sampling, was performed in male Sprague-Dawley rats (6-7 rats in each group) with 131I albumin as an intraperitoneal volume marker. Each rat was infused intraperitoneally with 25 mL of 1.5% glucose solution alone or 1.5% glucose solution containing hyaluronan at various molecular weights (MW-85 kD, 280 kD, 500 kD, and 4 MD) or containing hyaluronan of MW 500 kD at various concentrations (0.01%, 0.05%, 0.1%, 0.5%). Two additional groups were infused with 40 mL of 1.36% glucose dialysate alone or 1.36% glucose dialysate with 0.01% hyaluronan (MW 500 kD) to test the effect of hyaluronan when high dialysate fill volume was used. Addition of 0.01% hyaluronan significantly decreased peritoneal fluid absorption rate (K(E)) (by 22%, p < 0.01). The decrease was more marked with hyaluronan at high MW or high concentration, or with high dialysate fill volume. The net ultrafiltration tended to be higher in all hyaluronan groups compared to their control groups except in the 4 MD group; this difference was mainly due to a lower K(E) in all the hyaluronan groups. The direct lymphatic flow was significantly decreased in the 0.5% HA group. The transcapillary ultrafiltration rate (Qu) was significantly lower in the 4 MD group as compared to the control group. No difference in Qu was found between the other groups as compared to their control groups. (1) Intraperitoneal addition of hyaluronan may increase net peritoneal fluid removal, mainly because hyaluronan decreases peritoneal fluid absorption rate. The decrease was more marked when high dialysate fill volume was used, indicating that intraperitoneal addition of hyaluronan can prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume. (2) The decrease in peritoneal fluid absorption rate may be both MW-dependent and concentration-dependent: that is, a higher MW as well as a higher concentration of hyaluronan result in a more marked decrease in peritoneal fluid absorption rate. (3) Low concentrations of high MW hyaluronan may also decrease Qu. However, Qu did not decrease when high concentrations of hyaluronan were used despite a significant decrease in peritoneal fluid absorption rate.

The Standard Peritoneal Permeability Analysis in the Rabbit: A Longitudinal Model for Peritoneal Dialysis

The development of an experimental peritoneal dialysis (PD) model in rabbits to investigate peritoneal transport characteristics during a longitudinal follow-up and to assess normal values of these peritoneal transport parameters. Peritoneal transport parameters were determined in conscious, unrestrained rabbits by standard peritoneal permeability analysis adjusted for rabbits (SPAR). In this test a 1-hour dwell with 3.86% glucose dialysate is used. Dextran 70 (1g/L) was added to the dialysate to allow calculation of fluid kinetics. Dialysate samples were taken before, 10, and 40 minutes after instillation and at the end of the dwell. Blood was drawn at the end of the dwell. Eighteen female New Zealand White rabbits (2565 g) were included for catheter implantation. SPARs were performed in 15 animals; the other 3 were excluded due to complications. The mass transfer area coefficients (MTACs) of the low molecular weight solutes urea (MTAC(urea)) and creatinine (MTACcr) were calculated. The clearances of albumin (CIalb) and IgG (CI(IgG)), glucose absorption, and fluid transport were computed. Coefficients of intraindividual variation (Vc) were calculated for these parameters. The main complications were catheter obstruction and/or dislocation. Five rabbits underwent uncomplicated PD during a 4-week period. Fifteen SPARs in 15 stable rabbits were performed and analyzed to obtain normal values. Means and standard deviations of the transport parameters were as follows: MTAC(urea) 2.24+/-0.57 mL/min, MTACcr 1.61+/-0.30 mU/min, CI(alb) 52.9+/-17.2 microL/min, CI(IgG) 44.5+/-22.9 UL/min. The transcapillary ultrafiltration rate was 0.66+/-0.13 mL/min and the lymphatic absorption rate 0.47+/-0.26 mL/min. The parameters of solute transport were upscaled to those in humans using two different methods. MTACs of low molecular weight solutes in rabbits and patients were of the same order of magnitude, but the clearance of albumin was approximately four times higher in rabbits than in patients, and that of IgG eight times. In all rabbits sieving of sodium was observed. The dialysate/plasma (D/P) of sodium decreased to a minimum at 40 min (p<0.003 vs the initial value), followed by a rise to 60 min. The minimal value was 0.884+/-0.002. The coefficients of variation calculated on 7 rabbits that underwent two or more SPARs were similar to those assessed from the patient data. This indicates stability of the model and reproducibility of the SPAR. The conscious rabbit model for PD can be used for repeated studies on peritoneal transport.

Icodextrin with nitroprusside increases ultrafiltration and peritoneal transport during long CAPD dwells

Icodextrin with nitroprusside increases ultrafiltration and peritoneal transport during long CAPD dwells

Hyaluronan prevents the decreased net ultrafiltration caused by increased peritoneal dialysate fill volume

In the present study, we investigated (1) the effect of an increase in dialysate fill volume on peritoneal fluid and solute transport using a 1.36% glucose solution, and (2) the effect of intraperitoneal administration of hyaluronan on peritoneal transport characteristics when different fill volumes were used. A four-hour dwell study with frequent dialysate and blood sampling was performed in 26 male Sprague-Dawley rats with 131I albumin as the intraperitoneal volume marker. Each rat was injected intraperitoneally with 25 ml (group Con25, N = 6) or 40 ml (group Con40, N = 7) of 1.36% glucose dialysis solution alone or 25 ml (group HA25, N = 6) or 40 ml (Group HA40, N = 7) of 1.36% glucose dialysis solution with 0.01% hyaluronan. The peritoneal transport of fluid, glucose, urea, and total protein as well as the intraperitoneal hydrostatic pressure (IPP) with different fill volumes were evaluated. We found that IPP and peritoneal fluid absorption rate significantly increased with the increase in fill volume (P < 0.01), and therefore the net ultrafiltration volume was significantly lower in the Con40 group compared to the Con25 group despite a higher transcapillary ultrafiltration rate in the Con40 group. The addition of hyaluronan to dialysate significantly (P < 0.01) decreased the peritoneal fluid absorption rate (by 22% in HA25 vs. Con25 and by 29% in HA40 vs. Con40) and thus significantly increased the net peritoneal fluid removal. The diffusive mass transport coefficients for glucose, urea and total protein did not differ between the Con25 and Con40 groups or between the two hyaluronan groups as compared to their respective control groups. The peritoneal clearance of urea increased significantly in the high fill volume group (by 58% in Con40 vs. Con25) and in the two hyaluronan groups (by 21% in HA25 vs. Con25 and by 16% in HA40 vs. Con40). We conclude that: (1) An increase in dialysate fill volume using 1.36% glucose dialysis solution results in higher intraperitoneal hydrostatic pressure and higher peritoneal fluid absorption rate, and therefore lower net ultrafiltration. (2) Intraperitoneal addition of hyaluronan significantly decreases the peritoneal fluid absorption rate, and the decreasing effect is even more marked when a high fill volume is used. (3) Small solute clearances increase markedly with increases in fill volume, and then further increase by adding hyaluronan to the dialysate due to the increase in drainage volume. Thus, intraperitoneal administration of hyaluronan during a single peritoneal dialysis exchange may significantly increase the peritoneal fluid and solute removal by decreasing peritoneal fluid absorption, and may thereby prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume.

Day-to-day variability of fluid and solute transport in upright and recumbent positions during CAPD.

The effect of posture on peritoneal transport characteristics during CAPD is unpredictable because (1) although the capillary pressure is higher in the upright position, the intraperitoneal pressure is also elevated, and (2) the contact of dialysate with the subdiaphragmatic lymphatics is probably more extensive during recumbency. In eight CAPD patients, six peritoneal permeability tests (4 h, glucose 2.27%, dextran 70 as volume marker) were performed within 2 weeks, while the body posture was either recumbent (3 tests) or upright (3 tests). In addition, intraperitoneal pressure measurements were done in the recumbent and upright positions. The intraperitoneal pressure, not corrected for the contribution of the hydrostatic column, was higher in upright position (12.6 +/- 0.8 mmHg, mean +/- SEM) than during recumbency (6.7 +/- 0.8; P < 0.0005). Net ultrafiltration rate was lower when upright: 0.96 +/- 0.09 ml/min/1.73 m2, compared to 1.14 +/- 0.12 in the supine position (P < 0.05). This was achieved because the effective lymphatic absorption rate was marginally higher and the transcapillary ultrafiltration rate was slightly lower in the upright position. The mass transfer area coefficient of creatinine, representing effective peritoneal surface area, decreased from 10.7 +/- 1.3 ml/min/1.73 m2 (recumbent) to 9.9 +/- 1.4 (upright; P = 0.08). The clearances of five serum proteins decreased more the higher the molecular weight. As a consequence the restriction coefficient was 2.07 +/- 0.09 (recumbent) vs 2.23 +/- 0.08 (upright; P = 0.06). Hence the intrinsic permeability to macro-molecules was higher during recumbency. The intraperitoneal pressure was correlated with the net ultrafiltration rate (r = -0.71, P = 0.05) only during recumbency. In upright position relations were found between the effective lymphatic absorption rate and the mass transfer area coefficients of low molecular solutes. The coefficients of variation of fluid and solute parameters were not different between both positions. It is concluded that the decrease in net ultrafiltration rate in the upright position is only small and probably caused by counteracting effects of a higher intra-abdominal pressure and the effect of gravity. The upright position also led to only small decreases in solute transport parameters.

Effect of increased dialysate fill volume on peritoneal fluid and solute transport

It has recently been recommended that the peritoneal dialysate volume should in general be increased to increase the peritoneal small solute clearances. However, the net ultrafiltration volume may decrease due to higher intraperitoneal hydrostatic pressure (IPP) and higher peritoneal fluid absorption induced by higher fill volume. In the present study, we investigated the effects of increasing the fill volume on peritoneal fluid and solute transport. A four-hour dwell study with frequent dialysate and blood sampling was performed in 32 male Sprague-Dawley rats using 16 ml, 25 ml, 30 ml or 40 ml (8 rats in each group) of 3.86% glucose solution with 131I albumin as an intraperitoneal volume marker. The peritoneal transport of fluid, glucose, urea, sodium, potassium, phosphate and total protein as well as IPP with different fill volume were evaluated. The IPP and peritoneal fluid absorption rate (as estimated from the 131I albumin elimination coefficient, KE) significantly increased with increase in fill volume (P < 0.05), whereas the direct lymphatic absorption did not change with increasing fill volume. There was a strong correlation between IPP and KE. However, the net ultrafiltration volume was significantly higher in the high fill volume groups compared to the low fill volume groups, mainly due to a better maintenance of the dialysate to plasma glucose concentration gradient in the high fill volume groups. There was no significant difference in the diffusive mass transport coefficients (KBD) and sieving coefficients for any of the investigated solutes, although KBD values tended to be lower in the 16 ml group. The clearances for small solutes increased with increased fill volume, although these increases were slightly smaller than predicted from the increase in fill volume. We conclude that: (1) An increase in dialysate fill volume using 3.86% glucose solution results in higher intraperitoneal hydrostatic pressure and higher peritoneal fluid absorption, but, on the other hand, a higher net ultrafiltration; (2) The increase in net ultrafiltration with increased fill volume is mainly due to a better maintenance of glucose concentration in the dialysate, inducing an increased transcapillary ultrafiltration rate; (3) Solute clearances increase although not quite to the same extent as predicted from the increase in fill volume. Our results indicate that decreased net ultrafiltration volume associated with higher dialysate fill volume (due to higher IPP and higher peritoneal fluid absorption) could be avoided if hypertonic glucose solutions are used.

The nitric oxide donor nitroprusside intraperitoneally affects peritoneal permeability in CAPD

Nitroprusside is a nitric oxide (NO) donor. To investigate effects of nitroprusside i.p. on peritoneal permeability and perfusion, standard peritoneal permeability analyses were performed. Ten stable CAPD patients were studied twice within one week with glucose based dialysate (1.36% Dianeal) with and without addition of nitroprusside 4.5 mg/liter. Mass transfer area coefficients (MTAC) of CO2 were calculated to estimate peritoneal blood flow. Nitrate, a stable metabolite of NO, and cGMP, a second messenger of NO synthesis, were measured in plasma and dialysate. The MTACs of low molecular weight solutes were greater with nitroprusside (NP) compared to the control dwell (C): creatinine median 14.1 (NP) versus 9.9 ml/min (C), urea 21.7 (NP) versus 18.5 ml/min (C) and urate 10.5 (NP) versus 8.6 ml/min (C) (P < 0.05 for all). This points to an increased effective peritoneal surface area with nitroprusside. Furthermore, the restriction coefficient for the low molecular weight solutes decreased from 1.28 (C) to 1.23 (NP) (P = 0.02), suggesting some effect also on the size selectivity to these solutes. The effect of nitroprusside on the clearances of serum proteins was more pronounced. The increase with nitroprusside was 34% for beta 2-microglobulin, 70% for albumin, 77% for IgG and 143% for alpha 2-macroglobulin. This reduction in size selectivity was reflected in a decrease in the restriction coefficient for macromolecules from 2.29 (C) to 1.86 (NP), P < 0.01. This implies an increase in the intrinsic permeability of the peritoneal membrane. Kinetic modeling, using computer simulations, was done to analyze these effects in terms of the pore theory, using a convection model and a diffusion model for the transport of macromolecules. Nitroprusside led to an increase of both the large pore radius and the small pore radius and of the unrestricted area over diffusion distance. These effects were more pronounced with the diffusion model. The MTAC CO2 was not different: NP 76.9 and C 84.1 ml/min. MTACs of nitrate were not greater than expected on the basis of the molecular weight during both dwells. The dialysate/plasma (D/P) ratio of cGMP was greater after addition of nitroprusside: 0.36, range 0.21 to 0.77 (C) and 0.74, 0.23 to 2.50 (NP), P = 0.02. With nitroprusside the D/P ratio of cGMP was greater than expected on the basis of its molecular weight (P < 0.001). This points to local generation of cGMP after the addition of nitroprusside, induced by NO. No differences were found in the dialysate concentrations of the prostaglandins (PG) PGE2 and 6-keto-PGF1 alpha and thromboxane B2 after addition of nitroprusside. The transcapillary ultrafiltration rate and the net ultrafiltration rate during four hours were not different with nitroprusside. In conclusion, nitroprusside i.p. increased the effective peritoneal surface area and the intrinsic permeability, but the peritoneal blood flow did not change. The greater than expected D/P ratios of cGMP point to local generation of cGMP with nitroprusside, induced by NO.

Peritoneal transport characteristics with glucose polymer based dialysate

Dialysate fluids containing glucose polymers as osmotic agent are different from the conventional solutions, because they are iso-osmotic to plasma and produce transcapillary ultrafiltration (TCUF) by colloid osmosis. To investigate the effects on fluid and solute kinetics, a comparison was made between a 7.5% glucose polymer based dialysate (icodextrin) and 1.36% and 3.86% glucose based dialysate in 10 stable CAPD patients. In each patient three standard peritoneal permeability analyses (SPA) were done with the osmotic agents and concentrations mentioned above. Dextran 70 was added to the glucose solutions to calculate fluid kinetics. In the glucose polymer SPAs fluid kinetics were calculated from the dilution and disappearance of dextrin. The TCUF rate with icodextrin was closer to that obtained with 3.86% glucose than to 1.36% glucose. Extrapolation of the fluid profiles revealed sustained ultrafiltration with icodextrin. TCUF increased linearly in time in the icodextrin tests, whereas a hyperbola best described the glucose profiles. The effective lymphatic absorption rate with icodextrin was similar to the glucose based solutions. Mass transfer area coefficients of low molecular weight solutes with icodextrin were also similar to the values obtained with glucose, as was D/P creatinine. A positive correlation was present between the MTAC creatinine and the TCUF rate with icodextrin (r = 0.66, P = 0.05), which was absent in the glucose SPAs. This suggests that in patients with a larger effective peritoneal surface area, more ultrafiltration can be achieved by glucose polymer solutions. Clearances of beta 2-microglobulin (beta 2m) were higher with icodextrin than with 3.86% glucose and 1.36% glucose dialysate (P < 0.05). No differences were found for the larger serum proteins albumin, IgG and alpha 2-macroglobulin. Initial D/PNa-->was higher (0.96) with icodextrin than with the glucose based solutions (0.92), due to the higher Na+ concentration of icodextrin, and it remained unchanged during the dwell. In contrast, D/PNa+ of 1.36% glucose increased during the dwell, whereas D/PNa+ decreased with 3.86% glucose until 60 minutes, followed by a subsequent increase. The ultrafiltration coefficient (UFC) of the total peritoneal membrane was assessed using 3.86% glucose (0.18 +/- 0.04 ml/min/mm Hg), and the UFC of the small pores was assessed using icodextrin (0.06 +/- 0.008 ml/min/mm Hg). The difference between these represented the UFC through the transcellular pores, which averaged 50.5% of the total UFC, but with a very wide range (0 to 85%). An inverse relation existed between the duration of CAPD treatment and the total ultrafiltration coefficient (r = -0.68, P < 0.04), which could be attributed to a lower UFC of the transcellular pores in long-term patients (r = -0.66, P < 0.05), but not to the UFC of the small pores (r = -0.48, NS). The TCUFRo-60 min through the transcellular pores correlated with the sodium gradient, corrected for diffusion, in the first hour of the dwell (r = 0.69, P < 0.04), indicating that both parameters indeed measure transcellular water transport. It can be concluded that the glucose polymer solution induced sustained ultrafiltration and had no effect on peritoneal membrane characteristics. In addition, the results of the present study support the hypothesis that the glucose polymer solutions exerts its osmotic pressure across intercellular pores with radii of about 40 A. This leads to increased clearances of low molecular weight proteins such as beta 2m that are transported through these pores without sieving of Na+. The latter, as found during 3.86% glucose dialysate, is probably caused by transcellular water transport. The transcellular water transport accounted for 50% of the total ultrafiltration with glucose based dialysis solutions. It was lower in long-term CAPD patients.

Fluid and solute transport in CAPD patients using ultralow sodium dialysate

Transcapillary ultrafiltration during CAPD is determined by the ultrafiltration coefficient of the peritoneal membrane and by Starling forces, the latter being mainly determined by the osmolality of the dialysate. Dialysate sodium concentration decreases during a dwell, implying that: (1) sodium passes the peritoneal membrane to a lesser extent than H2O, and (2) more H2O than sodium is removed in overhydrated patients. We therefore compared two dialysate solutions with similar osmolality, but different sodium concentration (Na+ 129 mmol/liter and 102 mmol/liter). Two peritoneal permeability tests (2 x 6 hrs, dextran 70 as volume marker) with an interval of two days were performed in 10 CAPD patients. Transcapillary ultrafiltration rate was higher with ultralow sodium dialysate (USD) than normal sodium dialysate (NSD): 1.80 +/- 0.16 ml/min versus 1.58 +/- 0.18 (P < 0.01). It was especially higher during the last two hours of the dwell: 0.49 +/- 0.12 ml/min (USD) versus 0.27 +/- 0.13 (NSD). The effective lymphatic absorption rate was not different: 1.01 +/- 0.12 ml/min (USD) versus 1.05 +/- 0.09 (NSD). Using two different kinetic models, the reflection coefficients for glucose, sodium and chloride were 0.032, 0.029 and 0.027 (for the convection model) and 0.033, 0.030 and 0.027 (for the diffusion model). As a consequence the decline in osmotic pressure was more gradual during the exchange with USD. The peritoneal membrane characteristics, that is the effective peritoneal surface area and the peritoneal restriction coefficient, were not altered by the composition of the dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of an increased intraperitoneal pressure on fluid and solute transport during CAPD

The effect of an increased intraperitoneal pressure on fluid and solute transport was studied in eight stable CAPD patients. Two permeability tests of two hours each with continuous registration of the intraperitoneal pressure were performed while patients were in supine position. The intra-abdominal pressure was raised by means of a tightening girdle with inflatable cuffs in one of the experiments. Intraperitoneally administered dextran 70 was used as a volume marker in order to determine the peritoneal fluid kinetics. The increment in the intra-abdominal pressure of 10.0 +/- 1.0 mm Hg caused a decline in the net ultrafiltration. This was mainly determined by an increase in the lymphatic absorption: 1.07 +/- 0.18 ml/min (without compression) versus 1.86 +/- 0.25 ml/min (with compression; P < 0.01), whereas the transcapillary ultrafiltration rate tended to decrease: 2.02 +/- 0.23 versus 1.73 +/- 0.27 ml/min (P = 0.08). External compression also diminished solute transport from the circulation to the peritoneal cavity. The decline in the mass transfer area coefficient of urea, creatinine, urate and beta 2-microglobulin was 13%, indicating a smaller effective peritoneal surface area caused by external compression probably due to a decrease in the number of the perfused peritoneal capillaries. The fall in the peritoneal protein clearances was more pronounced the higher the molecular weight of the protein, consistent with a decline in the intrinsic permeability of the peritoneum. Kinetic modeling using computer simulations was used to analyse these effects in terms of the pore theory, using a convection model (large pore radius 184 +/- 14 A) and a diffusion model (large pore radius 1028 +/- 218 A) for the transport of macromolecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dialysate osmolarity on the transport of low-molecular weight solutes and proteins during CAPD

Osmotic-induced fluid and solute transport was studied in ten stable CAPD patients, who were examined twice within one week, using dialysate with 1.36% glucose on the first and 3.86% glucose on the second day. Peritoneal fluid kinetics were determined using intraperitoneally administered dextran 70 as a volume marker. After a four-hour dwell period, an increase in mean transcapillary ultrafiltration rate (TCUFR) with 3.86% glucose compared to 1.36% glucose was found (3.40 +/- 0.62 ml/min vs. 1.20 +/- 0.57, P < 0.001), but the lymphatic absorption was unchanged (1.32 +/- 0.10 ml/min vs. 1.42 +/- 0.15). The increased TCUFR resulted in a higher clearance of beta 2-microglobulin, but no differences were present in the clearances of albumin, transferrin, IgG, IgA and alpha 2-macroglobulin. This is consistent with the two pore theory for transcapillary transport with a small pore size of less than 40 A. The contribution of osmotic induced convection to the total transport of beta 2-microglobulin was small (6% during 1.36% glucose, 16% during 3.86% glucose), suggesting that macromolecules are mainly transported by diffusion or hydrostatic convection. The peritoneal restriction coefficient was 2.37 +/- 0.04, indicating restricted diffusion for macromolecules. In contrast, the restriction coefficient for low-molecular weight solutes was 1.24 +/- 0.03, in accordance with a process of mainly unrestricted diffusion for solutes smaller than 16 A. Higher values of protein clearances were found during the first hour of dialysis compared with the subsequent hours.(ABSTRACT TRUNCATED AT 250 WORDS)