Dialysate to plasma solute concentration (D/P) versus peritoneal transport parameters in CAPD

The relationship between dialysate to plasma solute equilibrationratio (D/P) and diffusive (diffusive mass transport coefficients,K_BD) as well as convective (sieving coefficient, S, and netultrafiltration) transport characteristics were studied in clinicallystable CAPD patients and in patients with loss of ultrafiltrationcapacity (UFC). Forty-one 6-h single-dwell studies with standardglucose-based dialysis fluids containing 1.36/ (n = 9), 2.27%(n = 9), and 3.86% (n = 23) anhydrous glucose were carried outin 33 clinically stable CAPD patients. Eleven patients withloss of UFC were studied with 3.86% glucose solution. Intraperitonealdialysate volumes were calculated from the dilution of the tracer(¹³¹I-albumin) with a correction applied for its eliminationfrom the peritoneal cavity. K_BD and S were estimated using thePyle-Popovich-Moncrief model with aqueous plasma concentrations.A theoretical D/P curve was derived with and without takingconvective transport and peritoneal reabsorption into account. The three different glucose solutions yielded D/P curves whichwere similar for urea and potassium. For creatinine a slowerequilibration and for glucose and sodium a faster decrease indialysate concentration were observed with more hypertonic solutions.In general, there was a strong correlation which was best at240 min between D/P (for glucose dialysate/initial dialysateconcentration, D/D_o) and K_BD for all solutes (except sodium),whereas the correlation between D/P and convective transportparameters was much weaker. K_BD for creatinine (with 3.86% glucosesolution) could be estimated (r=0.98) from aqueous D/P usingthe experimental formula: creatinine K_BD= –1.8–In(1–D_24O/P)/0.1. Patients with loss of UFC due to increaseddiffusive transport (n = 8) could be discriminated from theclinically stable patients using K_BD and D/P (or D/Do) for creatinineand glucose or D/P for sodium. However, patients with loss ofUFC associated with increased peritoneal reabsorption (n = 2)could not be identified using these parameters. Theoreticallyderived D/P curves were in excellent agreement with measuredD/P for 1.36% glucose solution and simulations were satisfactoryalso for the 2.27% and 3.86% solutions provided that the effectof convective transport was taken into account. The standardized peritoneal equilibration test (PET) as proposedby Twardowski et al. [17] seems to be appropriately designedas regards duration of the dwell and the choice of glucose andcreatinine as investigated solutes. Thus, PET can be recommendedas a sensitive routine investigation for the monitoring of normal/abnormalperitoneal transport behaviour in peritoneal dialysis patients.     

Changes in free water fraction and aquaporin function with dwell time during continuous ambulatory peritoneal dialysis

Diffusive (K_BD, A₀/Δx(t)) transport parameters and sieving coefficients (S) for small solutes and free water fraction (FWF), that is, the fraction of total water flow that is transported through aquaporins, were assessed as functions of dwell time t for 35 continuous ambulatory peritoneal dialysis patients using glucose 3.86% dialysis fluid. The individual values of the unrestricted pore area over diffusion distance, A₀/Δx(t), were estimated using the mixed effects nonlinear regression and applied for evaluation of S(t) for sodium and FWF(t). FWF decreased on average from the initial 51% of the total transcapillary water flow to 36% at 120 min, whereas the small pore water fraction and sodium sieving coefficient increased. Our results were consistent with the three‐pore model if the contribution of the transcellular pores (α_TP) at the beginning of dwell study was doubled and later decreased to the standard value of 0.02. We conclude that transport characteristics of fluid and small solutes should be considered as time‐dependent variables during the peritoneal dialysis.     

A quantitative description of solute and fluid transport during peritoneal dialysis.

To investigate the relationship between dialysate glucose concentration and peritoneal fluid and solute transport parameters, 41 six-hour single dwell studies with standard glucose-based dialysis fluids containing 1.36% (N = 9), 2.27% (N = 9) and 3.86% (N = 23) anhydrous glucose were carried out in 33 clinically-stable continuous ambulatory peritoneal dialysis (CAPD) patients. Intraperitoneal dialysate volumes (VD) were determined from the dilution of 131I-albumin with a correction applied for its elimination from the peritoneal cavity (KE, ml/min). Diffusive mass transport coefficients (KBD) were calculated from aqueous solute concentrations (with a correction applied for the plasma protein concentration and, for electrolytes, also for the Donnan factor) during a period of dialysate isovolemia. The intraperitoneal amount calculated to be transported by diffusion was subtracted from the measured total amount of solutes in the dialysate, yielding an estimate of non-diffusive solute transport. The intraperitoneal dialysate volume over time curve was characterized by: initial net ultrafiltration (lasting on average 92 min, 160 min and 197 min and with maximum mean net ultrafiltration rates 6 ml/min, 8 ml/min and 14 ml/min, respectively, for the 1.36%, 2.27% and 3.86% solutions); dialysate isovolemia (lasting about 120 min for all three solutions) and fluid reabsorption (rate about 1 ml/min for all three solutions). KBD for glucose, potassium, creatinine, urea and total protein did not differ between the three solutions and the fractional absorption of glucose was almost identical for the three glucose solutions, indicating that the diffusive transport properties of the peritoneum is not influenced by the initial concentration of glucose or the ultrafiltration flow rate. About 50% of the total absorption of glucose occurred during the first 90 minutes of the dwell. The mean percentage of the initial amount of glucose which had been absorbed (%GA) at time t during the dwell could be described (r = 0.999) for all three solutions using the experimental formula %GA = 85 - 75.7 * e-0.005*t. After 360 minutes, about 75% of the initial intraperitoneal glucose amount had been absorbed corresponding to a mean (+/- SD) energy supply of 75 +/- 6 kcal, 131 +/- 18 kcal and 211 +/- 26 kcal for the three solutions. Non-diffusive (that is, mainly convective) transport was almost negligible for the less hypertonic solutions while it was estimated to account for 30 to 40% of the total peritoneal transport of urea, creatinine and potassium during the first 60 minutes of the 3.86% exchange.     

Solutes Transport Characteristics in Peritoneal Dialysis: Variations in Glucose and Insulin Serum Levels

Background. Differences in small solutes transport rate (SSTR) during peritoneal dialysis (PD) may affect water and solutes removal. Patients with high SSTR must rely on shorter dwell times and increased dialysate glucose concentrations to keep fluid balance. Glucose absorption during peritoneal dialysis (PD), besides affecting glucose and insulin metabolism, may induce weight gain. The study aimed at examining acute glucose and insulin serum level changes and other potential relationships in PD patients with diverse SSTR. Methods. This cross-sectional study used a modified peritoneal equilibration test (PET) that enrolled 34 prevalent PD patients. Zero, 15, 30, 60, 120, 180, and 240-minute glucose and insulin serum levels were measured. Insulin resistance index was assessed by the homeostasis model assessment (HOMA-IR) formula. SSTR categories were classified by quartiles of the four-hour dialysate/serum creatinine ratio (D₄/P_Cr). Demographic and clinical variables were evaluated, and the body mass index (BMI) was estimated. Correlations among variables of interest and categories of SSTR were explored. Results. Glucose serum levels were significantly different at 15, 30, and 60 minutes between high and low SSTR categories (p?=?0.014, 0.009, and 0.022). Increased BMI (25.5 ± 5.1) and insulin resistance [HOMA-IR?=?2.60 (1.40–4.23)] were evidenced overall. Very strong to moderate correlations between insulin levels along the PET and HOMA-IR (r?=?0.973, 0.834, 0.766, 0.728, 0.843, 0.857, 0.882) and BMI (r?=?0.562, 0.459, 0.417, 0.370, 0.508, 0.514, 0.483) were disclosed. Conclusions. Early glucose serum levels were associated with SSTR during a PET. Overweight or obesity and insulin resistance were prevalent. An association between insulin serum levels and BMI was demonstrated.     

Peritoneal transport in CAPD patients with permanent loss of ultrafiltration capacity

During a 10 year period, 14 out of 227 patients (6.2%) undergoing continuous ambulatory peritoneal dialysis (CAPD) developed permanent loss of ultrafiltration capacity (UFC). The risk of UFC loss increased from 2.6% after one year to 30.9% after six years of treatment. A six hour, single dwell study with glucose 3.86% dialysis fluid was carried out in nine of the UFC loss patients and in 18 CAPD patients with normal UFC. Intraperitoneal dialysate volumes were calculated using 131I-tagged albumin (RISA) as volume marker with a correction applied for its elimination from the peritoneal cavity. The RISA elimination coefficient (KE), which can serve as an estimation of the upper limit of the lymphatic flow, was also calculated. Diffusive mass transport coefficients (KBD) for investigated solutes (glucose, creatinine, urea, potassium, total protein, albumin and beta 2-microglobulin) were calculated during a period of dialysate isovolemia. Two patterns of UFC loss were observed: (a) seven patients had high KBD values for small solutes resulting in rapid uptake of glucose, whereas KBD values for proteins were normal; (b) two patients had normal KBD values but a threefold increase both in the fluid reabsorption rate and KE. We conclude that loss of the osmotic driving force (due to increased diffusive mass transport for small solutes) and increased fluid reabsorption (possibly due to increased lymphatic reabsorption) are the two major causes of permanent loss of UFC in CAPD patients.     

Albumin-based Solutions for Peritoneal Dialysis: Investigations with a Rat Model

Abstract: To evaluate albumin, an osmotic agent for peritoneal dialysis, the peritoneal fluid and solute transport were investigated during a 4-h single cycle peritoneal dialysis with albumin-based dialysis solutions. Two different albumin solutions were used in 15 normal Sprague-Dawley rats: isotonic 7.5% albumin solution (ADS 1, n = 7) and a combined 7.5% albumin and 1.36% glucose solution (ADS 2; n = 8). A standard 1.36% Dianeal solution was used to provide control values (n = 6). The rate of the intraperitoneal volume change (Q_v) was positive during the initial 90 min with ADS 2 and during the initial 60 min with Dianeal 1.36% solution but negative with ADS 1. The peritoneal bulk flow reabsorption rate, Q_a, was similar in all three groups. The estimated rate of transcapillary ultrafiltration (Q_u=Q_v+Q_j was positive with all three solutions throughout the dialysis. With ADS 1, Q_u increased gradually during the initial 90 min and then remained stable, but it decreased with ADS 2 and Dianeal 1.36% solution. Q_u with ADS 2 did not differ from that with Dianeal 1.36% solution during the initial 60 min, but it was significantly higher during the latter part of dialysis. The value of Q_u during the last 2 h of dialysis was 0.026 ± 0.010 and 0.025 ± 0.009 ml/min with ADS 1 and ADS 2, respectively, and it was significantly higher than that with Dianeal 1.36% solution (0.005 ± 0.007 ml/ min; p< 0.017). After 4 h of dialysis, 76.1 ± 10.2 and 78.8 ± 11.1% of the initial amount of albumin remained in the peritoneal cavity with ADS 1 and ADS 2, respectively. Since a positive value of Q_u was maintained for at least 4 h during dialysis with the two albumin-based solutions and was significantly higher after 4 h of dialysis than with the Dianeal 1.36% solution, and since (Q_a) was similar with the three solutions, the present findings indicate that the differences in the Q_v values are due to the differences in the transcapillary ultrafiltration rate (Q_U). Furthermore, ADS 2, a solution containing both crystalloid and colloid osmotic agents, resulted in higher and more prolonged ultrafiltration than did the conventional glucose solution. After 4 h of dialysis, about 20–25% of the initial amount of albumin was absorbed, indicating that albumin-based dialysis solutions may compensate for the protein loss into dialysate in continuous ambulatory peritoneal dialysis (CAPD) patients. The results of the present study may provide useful reference data in the evaluation of alternative osmotic agents.     

Evaluation of an experimental rat model for peritoneal dialysis: fluid and solute transport characteristics

The aim of this study was to develop a reference model of fluidand solute transport during experimental peritoneal dialysisin rats, which would simulate the conditions of clinical dialysisin CAPD patients as much as possible. For this purpose a 4-hdialysis study was performed in 13 normal Sprague-Dawley ratswith conventional glucose solutions (Dianeal 1.36% solution,n=6 and Dianeal 3.86% solution, n=7) and a protocol and methodslike those used in clinical dwell studies. The dilution of amarker, radioactive human serum albumin (RISA), was used todetermine the intraperitoneal dialysate volume with correctionsfor the elimination of RISA from the peritoneal cavity and samplevolumes. The isovolumetric method was employed to calculatethe diffusive mass transport coefficients. To compare our datawith reference values in CAPD patients, the data were scaledby a factor calculated as a ratio of the dialysate volume inCAPD to the dialysate volume in the rats. In a separate seriesof experiments the intraperitoneal hydrostatic pressure wasmonitored with increasing infusion volumes. The fluid transport characteristics, described as the percentagechanges of the initial intraperitoneal volume, were essentiallycomparable to those in CAPD patients. However, the intraperitonealvolume curves were shifted more to the left than were the reportedvalues in CAPD patients. The scaled diffusive mass transportcoefficient for urea was similar to that in CAPD patients. However,the transport of other solutes, in particular glucose, was fasterin the rats than in CAPD patients. The intraperitoneal hydrostaticpressure increased exponentially with increasing infusion volumerelative to body weight and was 0.3–0.9 mmHg with thestandard infusion volume of 30 ml in the present study. Theintraperitoneal hydrostatic pressure in the rats receiving 30mi of fluid intraperitoneally was lower than the reported intraperiCorrespondencetoneal pressure in CAPD patients using 2 1 of dialysis fluid. We conclude that the present experimental model of peritonealdialysis in the rat with a protocol and methods similar to thoseused in clinical studies, after appropriate scaling, seems tohave fluid and solute transport characteristics that resembledthose in clinical peritoneal dialysis, but considerable differenceswere also found.     

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.     

High peritoneal residual volume decreases the efficiency of peritoneal dialysis

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.     

Increased peritoneal permeability is associated with decreased fluid and small-solute removal and higher mortality in CAPD patients

Background: Recent studies suggest that increased peritoneal membrane permeability is associated with higher morbidity and mortality in peritoneal dialysis patients. It is not known, however, whether the difference in clinical outcome among different peritoneal transport groups is due to differences in peritoneal fluid and solute removal. In the present study, we compared the peritoneal fluid and solute transport and clinical outcome in CAPD patients with high (H), high-average (H-A), low-average (L-A) and low (L) peritoneal transport patterns. Design: A 6-h study was performed in 46 patients with frequent dialysate and plasma samples using 21 of 3.86% glucose dialysate with ¹³¹I albumin as an intraperitoneal volume marker. The patients were divided into four transport groups according to their D/P of creatinine at 240 min. Results: The results showed that high transporters had significantly lower peritoneal fluid and small-solute removal but high glucose absorption and high protein loss during a 6-h exchange. The serum albumin was lower and blood pressure and triglycerides were higher in high transporters compared with the other groups. Two-year patient survival from the start of CAPD treatment was significantly lower for high transporters (64, 85, 90 and 100% for H, H-A, L-A and L respectively, P<0.01). The 1-year patient survival from the dwell study was also significantly lower in high transporters (16, 63, 90 and 100% for each group, P<0.01). Conclusion: Our results suggest that high transporters remove less fluid and small solutes and have higher protein loss and increased glucose absorption. These alterations may contribute to fluid overload, malnutrition and lipid abnormalities that perhaps contribute to the increased mortality among the high transporters. Key words: CAPD, adequacy, peritoneal transport, mortality      

Optimizing peritoneal dialysis prescription for volume control: the importance of varying dwell time and dwell volume

Not only adequate uremic toxin removal but also volume control is essential in peritoneal dialysis (PD) to improve patient outcome. Modification of dwell time impacts on both ultrafiltration (UF) and purification. A short dwell favors UF but preferentially removes small solutes such as urea. A long dwell favors uremic toxin removal but also peritoneal fluid reabsorption due to the time-dependent loss of the crystalloid osmotic gradient. In particular, the long daytime dwell in automated PD may result in significant water and sodium reabsorption, and in such cases icodextrin should be considered. Increasing dwell volume favors the removal of solutes such as sodium due to the increased volume of diffusion and the recruitment of peritoneal surface area. A very large fill volume with too high an intraperitoneal pressure (IPP) may, however, result in back-filtration and thus reduced UF and sodium clearance. Based on these principles and the individual transport and pressure kinetics obtained from peritoneal equilibration tests and IPP measurements, we suggest combining short dwells with a low fill volume to favor UF with long dwells and a large fill volume to favor solute removal. Results from a recent randomized cross-over trial and earlier observational data in children support this concept: the absolute UF and UF relative to the administered glucose increased and solute removal and blood pressure improved.     

Quantification of free water transport in peritoneal dialysis

BACKGROUND: In peritoneal dialysis (PD) total net ultrafiltration (NUF) is dependent on transport through small pores and through water channels in the peritoneum. These channels are impermeable to solutes, and therefore, crystalloid osmotic-induced free water transport occurs through them. Several indirect methods to assess free water transport have been suggested. The difference in NUF between a 3.86% and a 1.36% solution gives a rough indication, but is very time consuming. The magnitude of the dip in dialysate/plasma (D/P) sodium in the initial phase of a 3.86% exchange is another way to estimate free water transport. In the present study, a method was applied to calculate free water transport by calculating sodium-associated water transport in one single 3.86% glucose dwell. METHODS: Forty PD patients underwent one standard peritoneal permeability analysis (SPA) with a 1.36% glucose solution, and another with a 3.86% glucose solution. At different time points intraperitoneal volume and sodium concentration were assessed. This made it possible to calculate total sodium transport. By subtracting this transport (which must have occurred through the small pores) from the total fluid transport, free water transport remained. These results were compared with the other methods to estimate free water transport. RESULTS: For the 1.36% glucose dwell, total transcapillary ultrafiltration in the first hour (TCUF(0-60)) was 164 mL, transport through the small pores was 129 mL, and free water transport was 35 mL (21%). For the 3.86% glucose solution, total TCUF(0-60) was 404 mL, transport through the small pores was 269 mL, and free water transport was 135 mL (34%). The contribution of free water transport in the first minute (TCUF(0-1)) was 39% of the total fluid transport. From the 40 patients, 11 patients had ultrafiltration failure (NUF <400 mL after 4 hours). For these patients the contribution of free water to TCUF(0-1) was significantly lower than for those with normal ultrafiltration (20% vs. 48%, P < 0.05). A strong correlation was present between free water transport as a percentage of total fluid transport and the maximum dip in D/P sodium (r= 0.84). The correlation was not significant with the difference in net ultrafiltration of 3.86% and 1.36% solutions (r= 0.24, P= 0.3). CONCLUSION: The method applied here is the first direct quantification of free water transport, calculated from a single standard peritoneal function test. It offers a quick possibility to evaluate patients suffering from ultrafiltration failure. In these patients free water transport was impaired, but the origin of this impairment is still to be determined.     

Effects of intraperitoneal heparin on peritoneal transport in a chronic animal model of peritoneal dialysis.

BACKGROUND: Heparin has anti-inflammatory effects and is often added to the peritoneal dialysis fluid to prevent fibrin formation. Conjugation of heparin to the surface of biomaterials has been shown to improve its biocompatibility. In this study, we describe for the first time an experimental chronic peritoneal dialysis model with repeated dwell studies in non-uraemic rats and evaluate the effect of addition of heparin to glucose-based peritoneal dialysis fluid on peritoneal fluid and solute transport. METHODS: Wistar male rats, weighing 340+/-15 g, with implanted peritoneal catheters were infused during 1 month, twice per day with 20 ml of Dianeal 1.36%+antibiotics (AB; n = 10) or Dianeal 1.36%+antibiotics+heparin 2500 U/l (HAB; n = 9). After 10 (DS 1) and 30 days (DS 2), a dwell study was performed in rats with free access to drinking water, by infusing 30 ml of Dianeal 3.86%. Dialysate samples were obtained at 0, 2, 30, 60, 120 and 240 min. Blood samples were drawn before and at the end of the dwell. Radiolabelled serum albumin was used as macromolecular volume marker. RESULTS: Peritoneal volumes during DS 1 were significantly greater for the HAB group as compared with the AB group. No differences in ultrafiltration were found during DS 2 for HAB vs AB. However, peritoneal volumes were significantly higher for DS 2 compared with DS 1 in the AB group. The amount of glucose absorbed over time did not differ between the solutions, while fluid absorption tended to be lower in the HAB group. CONCLUSIONS: Heparin may improve peritoneal fluid transport possibly due to better healing and reduced peritoneal inflammation as shown in this novel animal model of chronic peritoneal dialysis with repeated dwell studies.     

Influence of convection on the diffusive transport and sieving of water and small solutes across the peritoneal membrane

The three-pore model of peritoneal membrane physiology predicts sieving of small solutes as a result of the presence of a water-exclusive pathway. The purpose of this study was to measure the diffusive and convective components of small solute transport, including water, under differing convection. Triplicate studies were performed in eight stable individuals using 2-L exchanges of bicarbonate buffered 1.36 or 3.86% glucose and icodextrin. Diffusion of water was estimated by establishing an artificial gradient of deuterated water (HDO) between blood/body water and the dialysate. (125)RISA (radio-iodinated serum albumin) was used as an intraperitoneal volume marker to determine the net ultrafiltration and reabsorption of fluid. The mass transfer area coefficient (MTAC) for HDO and solutes was estimated using the Garred and Waniewski equations. The MTAC of HDO calculated for 1.36% glucose and icodextrin were similar (36.8 versus 39.7 ml/min; P = 0.3), whereas for other solutes, values obtained using icodextrin were consistently higher (P < 0.05). A significant increase in the MTAC of HDO was demonstrated with an increase in the convective flow of water when using 3.86% glucose (mean value, 49.5 ml/min; P < 0.05). MTAC for urea was also increased with 3.86% glucose. The identical MTAC for water using 1.36% glucose and icodextrin indicates that diffusion is predominantly through small pores, whereas the difference in MTAC for the remaining solutes is a reflection of their sieving. The increase in the MTAC of water and urea associated with an increase in convection is most likely due to increased mixing within the interstitium.     

Dioctyl sodium sulphosuccinate increases net ultrafiltration in peritoneal dialysis

Background. The surface-active substance dioctyl sodium sulphosuccinate (DSS) has been reported to increase the peritoneal clearances of urea and creatinine. This study investigated the effects of DSS on the fluid and solute transport characteristics of the peritoneum. Design. A 4-h single-dwell experiment session of peritoneal dialysis using 25 ml of 3.86% glucose dialysis solution with an intraperitoneal volume maker was performed in 16 male Sprague-Dawley rats. In eight rats, 0.005% (50 p.p.m.) DSS was added to the dialysis fluid. No DSS was given to the other eight rats (control group). The transport of fluid, glucose, potassium, sodium, urea, phosphate and urate were analysed. Results. There was a significant increase in the intraperitoneal volume in the DSS group (33.0±2.9 ml) was significantly higher compared to the control group (28.8±2.1 ml. P<0.01). This increase in the drain volume was mainly due to a decrease in peritoneal fluid absorption rate in the DSS group (0.040±0.013 ml/min) as compared to the control group (0.054±0.010 ml/min, P0.05). There was no significant difference in the diffusive permeability and sieving coefficient for the small solutes between these two group. However, the clearances for urea and sodium were higher in the DSS group, mainly due to the increase in the dialysate volume. Conclusion. Our results suggest that DSS significantly increases the net ultrafiltration of peritoneal dialysis. This effect, which was mainly due to a decrease in the fluid absorption rate, contributed to the increased clearances for urea and sodium. DSS did not alter the diffusive permeability and sieving coefficient for the small solutes.     

Volume stress-induced peritoneal endothelin-1 release in continuous ambulatory peritoneal dialysis

In long-term peritoneal dialysis, functional deterioration of the peritoneal membrane is often associated with proliferative processes of the involved tissues leading to peritoneal fibrosis. In continuous ambulatory peritoneal dialysis (CAPD), failure to achieve target values for adequacy of dialysis is commonly corrected by increasing dwell volume; in case of ultrafiltration failure, osmolarity of the dialysate gets increased. In a prospective study, the impact of increasing dwell volume from 1500 ml to 2500 ml per dwell (volume trial) or changing the osmolarity of the dialysate from 1.36 to 3.86% glucose (hyperosmolarity trial) on the peritoneal endothelin-1 (ET-1) release was analyzed. ET-1 is known to exert significant proliferative activities on a variety of cell types leading to an accumulation of extracellular matrix. A highly significant difference in the cumulative peritoneal ET-1 synthesis was found between the low- and high-volume exchange, whereas differences in the hyperosmolarity setting were only moderate. Sixty minutes after initiating dialysis, the cumulative ET-1 synthesis was 2367 +/- 1023 fmol for the 1500 ml versus 6062 +/- 1419 fmol for the 2500 dwell (P < 0.0001) and 4572 +/- 969 fmol versus 6124 +/- 1473 fmol for the 1.36 and 3.86% glucose dwell (P < 0.05), respectively. In conclusion, increasing dwell volume leads to a strong activation of the peritoneal paracrine endothelin system. Because ET-1, apart from being a potent vasoactive peptide, contributes to fibrotic remodeling, this study indicates that volume stress-induced ET-1 release might contribute to structural alteration of the peritoneal membrane in long-term peritoneal dialysis.     

Defining Peritoneal Dialysis Adequacy: Kt/Vurea Revisited

Background. Although adequate peritoneal dialysis is not well defined, Kt/Vurea has been used as an index, and various values have been proposed. However, conflicting evidence existed regarding the appropriateness of using Kt/Vurea to define dialysis adequacy and its optimal value. Therefore, the present study performed a theoretical analysis on whether we should use Kt/Vurea to define peritoneal dialysis adequacy and what the optimal value should be. Methods. The three-pore model was applied to evaluate the transport patterns of different molecular weight solutes and fluid. Optimal Kt/Vurea value was estimated based on urea kinetics and nitrogen balance. Results. The removal pattern of small solute, middle and large molecules, and fluid and sodium are quite different. Depending on the dwell time, higher urea removal does not necessarily mean higher sodium, fluid, and other molecular weight solute removals. To reach nitrogen balance, the dialysis doses and therefore Kt/Vurea values varied with different dietary protein intakes in a patient with a given weight and residual renal function. Conclusion. This study shows that Kt/Vurea in peritoneal dialysis cannot represent the removal of other solutes and fluid, indicating that Kt/Vurea alone should not be used as a sole indicator of peritoneal dialysis adequacy. The results also show that optimal Kt/Vurea cannot be a fixed value, but varies according to individual dietary protein intake and tolerable blood urea level.     

Peritoneal ultrafiltration and fluid reabsorption during peritoneal dialysis

Peritoneal ultrafiltration and fluid reabsorption characteristics for 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were investigated in single dwell studies of 6 h duration with 21 of 3.86% glucose dialysis fluid. Dialysate volumes were determined in situ using radioiodinated serum albumin (RISA) as volume marker with a correction applied for the total elimination of RISA from the peritoneal cavity. The RISA elimination rate was calculated as 2.1 +/- 0.5 ml/min. The true dialysate volume after 360 min was on average 28% less than the apparent volume calculated without correction for the elimination of RISA. The mean maximum true volume plus sampling losses was 3255 ml at 240 min, corresponding to a mean net ultrafiltration volume of 762 ml between 3 min and 240 min. The mean net fluid reabsorption rate between 240 min and 360 min was 1.2 +/- 0.7 ml/min. This study of standard dialysate volume/time curves in clinically stable CAPD patients using hypertonic dialysis fluid shows that about 90% of the total net ultrafiltration is achieved during the first 90 min of the dwell. After an extended period of dialysate isovolaemia, usually lasting as long as between 120 min and 240 min, fluid reabsorption is observed in all patients.     

Effects of anaesthesia on fluid and solute transport in a C57BL6 mouse model of peritoneal dialysis.

BACKGROUND: Genetically modified mice show promise as animal models for studying the physiology and pathophysiology of the peritoneum during peritoneal dialysis (PD). Methods for evaluation of the functional characteristics of the mouse peritoneum have not been studied extensively, and the effects of anaesthesia on fluid and solute transport in mouse models of PD are unknown. METHODS: A single exchange of dialysis solution was performed in C57BL6 mice by injecting fluid into the peritoneal cavity using a 27-gauge needle and allowing fluid to dwell for 30, 60 or 120 min. Experiments evaluated the effect of ketamine (plus xylazine) anaesthesia on fluid and solute transport; these effects were examined in separate experiments using glucose and mannitol as the osmotic agent added to the injected dialysis solution. After euthanasia, blood was collected, the remaining dialysis solution was drained and their contents analysed for concentrations of the osmotic solute (glucose or mannitol), urea nitrogen (UN), sodium (Na) and a volume marker (fluorescein-labelled albumin) added to the initial, injected dialysis solution. Determined parameters included final volume of dialysis solution (drained plus residual fluid volume), dialysate concentration (D/D0) of glucose (or D/D0 mannitol), dialysate-to-plasma concentration ratio for (D/P) UN and D/P Na and the apparent dialysis solution volume by indicator dilution. Peritoneal permeability-area (PA) values or mass transfer-area coefficients were also calculated for the osmotic solutes. RESULTS: Final volumes of dialysis solution were higher when mice were anaesthetized with ketamine than in unanaesthetized mice, independent of whether glucose or mannitol was used as the osmotic agent. The increases in final volume were paralleled by higher dialysate concentrations (D/D0 values) and lower calculated PA values for both glucose and mannitol. When using either osmotic agent, anaesthesia also increased plasma glucose concentrations, suggesting that ketamine altered glucose metabolism. CONCLUSIONS: Ketamine anaesthesia in the mouse decreases PA values for glucose and mannitol when used as osmotic agents in PD solutions. The decrease in transperitoneal transport for these osmotic agents increases the final volume of fluid which can be obtained from the peritoneal cavity.