Diffusive Mass Transport Coefficient Research Articles

Peritoneal Transport in Peritoneal Dialysis Patients Using Glucose-Based and Amino Acid-Based Solutions

To evaluate peritoneal transport of fluid and solutes in continuous ambulatory peritoneal dialysis (CAPD) patients using amino acid (AA)-based versus glucose-based dialysis solutions. Using iodine-labeled human serum albumin ((125)I-HSA) as intraperitoneal volume marker, peritoneal transport was investigated in a group of 20 clinically stable patients (11 females and 9 men, age 53 +/- 15 years) on CAPD for 15 - 101 months. Two paired 4-hour dwells, one with 1.36% glucose and one with 1.1% AA dialysis solution, were performed in each patient. Intraperitoneal dialysate volume, fluid absorption rate, and diffusive mass transport coefficients (K(BD)) and sieving coefficients (S) for glucose, creatinine, urea, potassium, and total protein were estimated for each dwell study. Dwell studies with AA solution were used to estimate K(BD) values for individual AAs. Intraperitoneal dialysate volume was higher for AA solution in comparison with glucose solution due to the higher osmolality of the AA solution. No statistically significant difference was found for K(BD) or S for creatinine, urea, potassium, or total protein in the dwell studies with either solution, whereas K(BD) for glucose was higher with AA than with glucose solution. Mean values of K(BD) of AA were similar but with high standard deviation, reflecting inter-individual variations in peritoneal transport rate. Our results indicate that the AA peritoneal transport rate is strongly dependent on transport characteristics of the individual peritoneal membrane.

Theoretical and Numerical Analysis of Different Adequacy Indices for Hemodialysis and Peritoneal Dialysis

Background: Apart from KT/V, equivalent urea clearance (EKR) and fractional solute removal (FSR) can also be used to assess the dialysis adequacy. Our objective was to analyze the relationships between these indices for different dialysis modalities and schedules, using urea kinetic modeling. Methods: EKR and FSR were calculated for HD (three or six times per week), automatic nightly PD (ANPD) and CAPD using the following reference values of urea concentration and mass in the body: peak, peak average, time average and treatment time average. Results: The standard KT/V approach is related to the treatment time average, whereas the standard EKR is related to the time average reference values. In spite of KT/V = 3.5 (K meaning dialyzer clearance or peritoneal diffusive mass transport coefficient), EKR and FSR were lower for ANPD and CAPD than for HD. The ratio of EKR to FSR was essentially the same for the different treatment modalities (range 3.48–4.07 ml/min). This could be explained by the theoretical analysis which predicts the value of EKR/FSR = V/Tc, independent of the treatment modality and schedules (V is a solute distribution volume, Tc is the time of the full dialysis cycle). Conclusion: Whereas the index KT/V in its standard form cannot be used to compare different dialysis regimens, EKR and FSR provide very similar evaluation of different dialysis modalities and schedules, and may be considered as equivalent measures for comparative studies of dialysis adequacy.

Comparison of Kinetic Characteristics of Amino Acid-Based and Dipeptide-Based Peritoneal Dialysis Solutions

A mixture of dipeptides (DP) has been proposed as alternatives (to glucose and amino acids, (AA)) osmotic agent in peritoneal dialysis (PD) solutions. DP based solutions may have metabolic and nutritional advantages compared to AA based solutions, as some sources of AA (such as tyrosine) are poorly soluble in water. In a previous study, we compared the kinetic characteristics of DP and AA based solutions; however, the amount of AA differed substantially. The aim of the present study was to compare solutions with almost equal amounts of AA. The following solutions were used: (1) amino acid (AA) solution containing leucine, valine, lysine, isoleucine, threonine, phenylalanine and histidine (tyrosine was omitted because of its poor solubility), (2) dipeptide (DP) solution containing leucyl-valine, lysyl-isoleucine, threonyl-phenylalanine and histidyl-tyrosine. Sixteen Sprague-Dawley rats were divided in two groups and were subjected to intraperitoneal injection of either 25 mL of AA (n=8) or DP solution. Dialysate and blood samples were taken frequently postinfusion for measurement of AA and DP concentrations as well as AA from DP. Kinetic models were developed for estimation of diffusive mass transport coefficient between peritoneal cavity and blood (K BD), DP hydrolysis rate coefficient (K H) and AA clearance in the body (K C). Calculations showed that K H is about ten times lower than K BD. Thus, hydrolysis rate in peritoneal cavity is much lower than the diffusive transport rate of DP. K BD for AA appeared to be similar to K BD for dipeptides. K C was much higher than K BD for AA. This finding explains the rapid clearance of amino acids from blood. Nevertheless, the AA-based solution resulted in much higher peak concentrations of AA in blood after 120 min of the dwell than AA concentrations achieved following the use of the DP-based solution. Peritoneal transport characteristics of AA and DP were similar; however their kinetics in blood differs substantially. The DP solution resulted in a less pronounced increase in AA concentrations in blood, suggesting that DP solution could provide AA in a more physiological way.

Fluid and Solute Transport in CAPD Patients before and after Permanent Loss of Ultrafiltration Capacity

Two major types of permanent loss of ultrafiltration capacity (UFC) were previously distinguished among patients treated with CAPD: 1) type HDR with high diffusive peritoneal transport rate of small solutes and low osmotic conductance,but with normal fluid absorption rate, and 2) type HAR with high fluid absorption rate, but with normal diffusive peritoneal transport rate of small solutes and normal osmotic conductance. However, the detailed pattern of changes in peritoneal transport parameters in patients developing loss of ultrafiltration capacity is not known. Analysis of solute and fluid transport parameters in the same patient before and after UFC loss. Seven CAPD patients who had undergone repeated dwell studies,which were carried out before and/or after the onset of UFC loss. Dialysis fluids (2 L) with glucose or a mixture of amino acids as osmotic agent at three basic tonicities were applied during 6 hour dwell studies. Fluid and solute transport parameters were previously shown not to be affected by these dialysis solutions (except by hypertonic amino acid-based solution). Intraperitoneal dialysate volume and fluid absorption rate were assessed using radiolabeled human serum albumin (RISA). Osmotic conductance (a(OS))was estimated by a mathematical model as ultrafiltration rate induced by unit osmolality gradient. Diffusive mass transport coefficients, K(BD), for glucose,urea,and creatinine were estimated using the modified Babb-Randerson-Farrell model. Five patients had increased K(BD) for small solutes after the onset of UFC loss,and three of them had decreased a(OS),whereas two patients had normal a(OS). In one of them, a(OS) decreased with time after the onset of UFC loss with concomitant normalization of glucose absorption. In all studies of these five patients the fluid absorption rate was within the normal range. Two other patients had increased fluid absorption rate (about 5 ml/min),and one of them also had increased K(BD) for small solutes,in two consecutive dwell studies in each patient with the second study being carried out at 1 and 7 months respectively after the first one. In all four studies in these two patients, the a(OS) was within the normal range. The sodium dip during dialysis with 3.86% glucose-based solution was lost, not only among most patients with UFC loss related to reduced osmotic conductance, but also in patients with increased K(BD). The occurrence of two major types of UFC loss was confirmed. However, a case of a mixed type of UFC loss with high fluid absorption rate and high K(BD) for small solutes, but normal osmotic conductance, and with normalization of initially high K(BD) for small solutes, linked with decreasing initially normal osmotic conductance,was also found. As a reduced sodium dip with hypertonic glucose solution is not only seen in patients with reduced osmotic conductance, it cannot reliably be used as a single measure of decreased aquaporin function. Permanent ultrafiltration capacity loss may be a dynamic phenomenon with a variety of alterations in peritoneal transport characteristics.

Functional and molecular characterization of a peritoneal dialysis model in the C57BL/6J mouse

Animal models are important for understanding the physiology and pathophysiology of peritoneal transport during peritoneal dialysis (PD). Mechanistic investigations of rat and rabbit models of PD are mostly based on intervention studies using pharmacologic agents or blocking antibodies. These models may be limited by the time-course, lack of specificity, or side effects of such interventions. Genetically modified mice could provide an attractive alternative to the above models. In this study, we have characterized PD parameters and tested the effect of gender and dialysate volume and/or osmolality in the C57BL/6J mouse. Mice were submitted to a 2-hour peritoneal equilibration test in order to obtain permeability parameters. The expression of the water channel aquaporin-1 (AQP1) and endothelial NO synthase (eNOS) was investigated at the protein (immunoblotting, immunostaining) and mRNA [real-time reverse-transcription-polymerase chain reaction (RT-PCR)] levels. The potential effect of gender on these parameters was also studied. Exposure of mice to 2 mL of 3.86% glucose dialysate yielded equilibration curves for urea and glucose, a sodium sieving, and a net ultrafiltration (UF) that were remarkably similar to those obtained in rats. The increase in dialysate volume (from 2 mL to 3 mL and 6 mL) resulted in a higher ultrafiltration and, for the highest volume, an increase in the diffusive mass transport coefficient (MTAC) for urea. The increase in dialysate glucose concentration (from 1.36% to 3.86% and 7%) resulted in increased sodium sieving and higher UF, whereas the MTAC for urea was unchanged. In comparison with males, females had a similar peritoneal transport rate for small solutes but a significantly lower sodium sieving, reflecting a lower AQP1 mRNA and protein expression in the peritoneum. These data demonstrate the structural and functional similarity between mouse and rat models of PD, and further emphasize the relevance of mouse models to understand PD in humans. They also suggest that gender may influence water transport and AQP1 expression in the peritoneum.

Peritoneal Fluid Transport in CAPD Patients with Different Transport Rates of Small Solutes

Continuous ambulatory peritoneal dialysis (CAPD) patients with high peritoneal solute transport rate often have inadequate peritoneal fluid transport. It is not known whether this inadequate fluid transport is due solely to a too rapid fall of osmotic pressure, or if the decreased effectiveness of fluid transport is also a contributing factor. To analyze fluid transport parameters and the effectiveness of dialysis fluid osmotic pressure in the induction of fluid flow in CAPD patients with different small solute transport rates. 44 CAPD patients were placed in low (n = 6), low-average (n = 13), high-average (n = 19), and high (n = 6) transport groups according to a modified peritoneal equilibration test (PET). The study involved a 6-hour peritoneal dialysis dwell with 2 L 3.86% glucose dialysis fluid for each patient. Radioisotopically labeled serum albumin was added as a volume marker.The fluid transport parameters (osmotic conductance and fluid absorption rate) were estimated using three mathematical models of fluid transport: (1) Pyle model (model P), which describes ultrafiltration rate as an exponential function of time; (2) model OS, which is based on the linear relationship of ultrafiltration rate and overall osmolality gradient between dialysis fluid and blood; and (3) model G, which is based on the linear relationship between ultrafiltration rate and glucose concentration gradient between dialysis fluid and blood. Diffusive mass transport coefficients (K(BD)) for glucose, urea, creatinine, potassium, and sodium were estimated using the modified Babb-Randerson-Farrell model. The high transport group had significantly lower dialysate volume and glucose and osmolality gradients between dialysate and blood, but significantly higher K(BD) for small solutes compared with the other transport groups. Osmotic conductance, fluid absorption rate, and initial ultrafiltration rate did not differ among the transport groups for model OS and model P. Model G yielded unrealistic values of fluid transport parameters that differed from those estimated by models OS and P. The K(BD) values for small solutes were significantly different among the groups, and did not correlate with fluid transport parameters for model OS. The difference in fluid transport between the different transport groups was due only to the differences in the rate of disappearance of the overall osmotic pressure of the dialysate, which was a combined result of the transport rate of glucose and other small solutes. Although the glucose gradient is the major factor influencing ultrafiltration rate, other solutes, such as urea, are also of importance. The counteractive effect of plasma small solutes on transcapillary ultrafiltration was found to be especially notable in low transport patients. Thus, glucose gradient alone should not be considered the only force that shapes the ultrafiltration profile during peritoneal dialysis. We did not find any correlations between diffusive mass transport coefficients for small solutes and fluid transport parameters such as osmotic conductance or fluid and volume marker absorption. We may thus conclude that the pathway(s) for fluid transport appears to be partly independent from the pathway(s) for small solute transport, which supports the hypothesis of different pore types for fluid and solute transport.

COMPARISON OF KINETIC CHARACTERISTICS OF AMINO ACID-BASED AND DIPEPTIDE-BASED PERITONEAL DIALYSIS SOLUTIONS

A mixture of dipeptides (DP) has been proposed as alternatives (to glucose and amino acids, (AA)) osmotic agent in peritoneal dialysis (PD) solutions. DP based solutions may have metabolic and nutritional advantages compared to AA based solutions, as some sources of AA (such as tyrosine) are poorly soluble in water. In a previous study, we compared the kinetic characteristics of DP and AA based solutions; however, the amount of AA differed substantially. The aim of the present study was to compare solutions with almost equal amounts of AA. Methods: The following solutions were used: (1) amino acid (AA) solution containing leucine, valine, lysine, isoleucine, threonine, phenylalanine and histidine (tyrosine was omitted because of its poor solubility), (2) dipeptide (DP) solution containing leucyl-valine, lysyl-isoleucine, threonyl-phenylalanine and histidyl-tyrosine. Sixteen Sprague-Dawley rats were divided in two groups and were subjected to intraperitoneal injection of either 25 mL of AA (n=8) or DP solution. Dialysate and blood samples were taken frequently postinfusion for measurement of AA and DP concentrations as well as AA from DP. Results: Kinetic models were developed for estimation of diffusive mass transport coefficient between peritoneal cavity and blood (K BD ), DP hydrolysis rate coefficient (K H ) and AA clearance in the body (K C ). Calculations showed that K H is about ten times lower than K BD . Thus, hydrolysis rate in peritoneal cavity is much lower than the diffusive transport rate of DP. K BD for AA appeared to be similar to K BD for dipeptides. K C was much higher than K BD for AA. This finding explains the rapid clearance of amino acids from blood. Nevertheless, the AA-based solution resulted in much higher peak concentrations of AA in blood after 120 min of the dwell than AA concentrations achieved following the use of the DP-based solution. Conclusions: Peritoneal transport characteristics ofAA and DP were similar; however their kinetics in blood differs substantially. The DP solution resulted in a less pronounced increase in AA concentrations in blood, suggesting that DP solution could provide AA in a more physiological way.

Distributed modeling of diffusive solute transport in peritoneal dialysis.

The diffusive transport between blood and an ex-tissue medium (dialysis fluid) is evaluated using a mathematical model that takes into account the (quasicontinuous) distribution of capillaries within the tissue at various distances from the tissue surface, and includes diffusive-convective transport through the capillary wall and lymphatic absorption from the tissue. General formulas for solute penetration depth, lambda, and for the diffusive mass transport coefficient for the transport between blood and dialysis fluid, K(BD), are provided in terms of local transport coefficients for capillary wall, tissue, and lymphatic absorption. For pure diffusive transport between blood and dialysis fluid and thick tissue layers (i.e., if the solute penetration depth is much lower than the tissue thickness) these formulas yield previously known expressions. It is shown that apparent tissue layers, with widths lambdaTBL and lambdaT, respectively, may be defined according to the values of local transport parameters in such a way that K(BD) is equal to the solute clearance K(TBL) from the tissue by blood and lymph for a layer with width lambdaTBL or to the solute clearance K(T) from blood to dialysate by diffusion through the tissue layer with width lambdaT. For tissue layers with width much higher than the penetration depth: lambdaT approximately = lambdaTBL approximately = lambda. These characteristic width lengths depend on the transport parameters (and thus on the size) of solutes. Effective blood flow, which may be related to the exchange of the solute between blood and dialysate, is defined using an analogy to the extraction/absorption coefficients for blood-tissue exchange. Various approximations for the distributed model formula for diffusive mass transport coefficient (K(BD)) are possible. The appropriate range for their application is obtained from the general formula.

Diffusive permeability of rabbit peritoneum for small solutes in vitro: effect of gentamicin and insulin.

The purpose of the in vitro study was to compare the diffusive transport of creatinine, uric acid and glucose, directed from the interstitial (I) to the mesothelial (M) side of the peritoneum and in the opposite direction, before (15-60min) and after (75-120min) application of gentamicin and insulin. The experiments were undertaken on the rabbit parietal peritoneum in a modified Ussing chamber. A mathematical model was used to calculate a diffusive permeability coefficient P (in cm/s) and a diffusive mass transport coefficient KH (in mL/min). In the basic experimental series without drugs, the dynamics of peritoneal transport for examined solutes remained constant and there were no differences between transport directions (I--> M and M--> I). Mean values of P+/-SEM (KH+/-SEM) were 3.06+/-0.32 (321.1+/-33.5), 2.09+/-0.29 (219.2+/-30.7) and 2.73+/-0.47 (286.7+/-49.6) for creatinine, uric acid and glucose, respectively. The introduction of gentamicin decreased glucose transport directed from the mesothelial to the interstitial side of the membrane by about 12%. After insulin application we observed the increase of creatinine and glucose peritoneal transport rate. For creatinine, the above augmentation was by about 31% for I--> M and 83% for M--> I direction. In these conditions, the glucose transport directed from the interstitial to the mesothelial side of membrane increased by about 24%. Generally, in vitro gentamicin decreases, but insulin increases the diffusive permeability of the peritoneum for some small solutes. We suppose that these findings may be important for the efficiency of peritoneal dialysis.

Intraperitoneal atrial natriuretic peptide increases peritoneal fluid and solute removal

Atrial natriuretic peptide (ANP) is a hormone with well-known diuretic and vasodilating properties. Recently it was reported that ANP could increase the peritoneal fluid formation and increase peritoneal solute clearance. This study investigated the effect of ANP on peritoneal fluid and solute transport characteristics. Eighteen male Sprague-Dawley rats were divided into three groups. A four-hour dwell study using 25 mL 2.27% glucose dialysis solution with 50 microg/kg ANP (N = 6, H-ANP) or 5 microg/kg ANP (N = 6, L-ANP) or without ANP (N = 8, control) and frequent dialysate and blood sampling was done in each rat. Radiolabeled human albumin (RISA) was added to the solution as an intraperitoneal volume marker. The intraperitoneal volume was significantly higher in the H-ANP group as compared with the control group and the L-ANP group. The drainage volume was 26.2 +/- 1.1, 25.5 +/- 0.7, and 29.8 +/- 0.8 mL for the control, L-ANP, and H-ANP groups, respectively (P < 0.01). This was related to significant differences in the peritoneal fluid absorption rates (K(E); estimated as the RISA elimination coefficient): 39 +/- 3, 38 +/- 3, and 19 +/- 4 microL/min, and in the direct lymphatic absorption rate (K(EB); estimated as the clearance of RISA from dialysate to blood): 7 +/- 1, 6 +/- 1, and 4 +/- 1 microL/min for the control, L-ANP, and H-ANP groups, respectively (all P < 0.01). No differences were found in the intraperitoneal volume, K(E), and K(EB) between the control group and the L-ANP group. The diffusive mass transport coefficient (K(BD)) for urea, sodium, potassium, and total protein did not differ among the three groups. However, the glucose D/D(0) was significantly higher, and the K(BD) for glucose was significantly lower in the H-ANP group as compared with the other two groups. Solute clearances (+175% for sodium and +26% for potassium) were significantly increased in the H-ANP group, mainly as a result of the increased fluid removal in this group. Our results suggest that ANP may decrease peritoneal fluid absorption (by 51%, partially because of decreasing the direct lymphatic absorption), resulting in a significant increase in peritoneal fluid removal and small solute clearances. While the basic diffusive permeability of the peritoneal membrane was not changed, the peritoneal glucose absorption was retarded by adding ANP to peritoneal dialysate, perhaps through interaction of ANP with glucose metabolism.

Kinetic modeling of fluid and solute transport in peritoneal dialysis.

Mathematical models for fluid and solute transport during peritoneal dialysis are described. A model for the transport of the so-called volume marker enables the correct estimation of the kinetics of the intraperitoneal dialysate volume as well as the rate of peritoneal fluid absorption. On the basis of these estimations, the solute transport components (diffusion, convective solute transport with ultrafiltrate and peritoneal solute absorption) may be separated within the net solute transport using a modified version of the Babb-Randerson-Farrell (BRF) model. The diffusive mass transport coefficient and sieving coefficient are given by the model. A simplified method for the estimation of the diffusive mass transport coefficient during the so-called isovolemia period is also described and compared to the BRF modeling. The three-pore model and the distributed model, which describe the structure-function relationship for the peritoneum, are also addressed.

Discriminative Impact of Ultrafiltration on Peritoneal Protein Transport

The dialysate concentration of large proteins increases, on average, linearly during the whole peritoneal dialysis dwell, and this linear pattern seems to be independent of the rate of ultrafiltration induced by dialysis fluid. However, we observed a high variability of protein kinetics in individual dwell studies. Therefore, we studied the details of the kinetic pattern of peritoneal transport. Kinetics of beta2-microglobulin, albumin, and total protein was examined in 23 clinically stable continuous ambulatory peritoneal dialysis patients using Dianeal 3.86% (15 dwell studies) or Dianeal 1.36% (9 dwell studies) dialysis fluid. Dialysate volume was measured using radioisotopically labeled albumin as a volume marker, with corrections for sample volume and absorption of fluid and marker from the peritoneal cavity. The generalized version of the Babb-Randerson-Farrell model was applied to estimate diffusive mass transport coefficient (K(BD)) and sieving coefficient (S) for proteins and small solutes (urea, creatinine, glucose, sodium, potassium). To quantify deviations from the linear pattern of protein dialysate concentration increase, the ratio (SR) of the slope of the linear regression line for the initial 3-30 minutes, divided by the slope for the next 60 - 360 minutes, was evaluated for albumin. In 5 dwell studies with Dianeal 3.86% fluid, SR was lower than 1 [low albumin transport (LAT) group, median SR = 0.49, range -4.39 - 0.71], while in the other 10 dwell studies with this solution, SR was higher than 1 [high albumin transport (HAT) group, median SR = 2.77, range 1.32 - 7.56]. Clearances of albumin up to 120 minutes were higher in the HAT group than in the LAT group. The transport of fluid, beta2-microglobulin, and small solutes did not differ between the LAT and the HAT groups. K(BD) values for proteins did not differ between the groups, but S values for albumin and total protein were lower for the LAT group than for the HAT group. A similar diversity was found in the dwell studies with Dianeal 1.36%: In three dwell studies, SR for albumin was lower than 1 (median SR = 0.95, range 0.70 - 0.97), and in six dwells it was higher than 1 (median SR = 1.55, range 1.23 - 1.98). In general, the SR values observed with Dianeal 1.36% were closer to 1 than those for Dianeal 3.86%. Ultrafiltration may affect the initial kinetic patterns of large protein (such as albumin) transport in two opposing ways: (1) by slowing the increase of protein concentration in dialysate (due to a low sieving coefficient, LAT group), and (2) by speeding up the increase of protein concentration in dialysate (due to a high sieving coefficient, HAT group). The average pattern in a non-selected group of studies is, however, close to a steady (linear) increase.

Peritoneal Transport of Glucose in Rat

To evaluate the convective transport characteristics of glucose and the effect of high glucose and insulin during experimental peritoneal dialysis in rat. Male Sprague-Dawley rats weighing 300-400 g were used in this study. Mannitol (5%) was used as osmotic agent. Glucose was added to dialysis solution to yield a concentration of 100 mg/dL (group 1) or 300 mg/dL (group 2). Mannitol solution (5%) containing the same concentration of electrolytes and lactate but without glucose was used as control (group 3). In group 2, blood sugar was maintained at approximately 300 mg/dL by continuous intravenous infusion of 25% glucose solution and 0.9% NaCl solution. A 2-hour dwell study was performed with 30 mL of test solutions. Intraperitoneal volume was calculated by volume marker (18.5 kBq of 131I-human radioiodinated serum albumin, RISA) dilution with corrections made for the elimination of RISA from the peritoneal cavity (K(E)) and sample volume. The diffusive mass transport coefficient (K(BD)) and sieving coefficient (S(BRF)) were calculated by using the Babb-Randerson-Farrell model. S was also calculated directly by using isocratic methods (S(I)). The peritoneal fluid absorption rate (K(E)) was taken into account for the calculation of S(I). Intraperitoneal volume was significantly higher in group 2 compared with groups 1 and 3. Peritoneal fluid absorption rate, K(E), was similar in all three groups. S(BRF) and S(I) for glucose were significantly lower in group 2 compared with groups 1 and 3. S(BRF) for glucose in group 2 was below zero and S(I) near zero. K(BD) for glucose was significantly higher in group 2 than in groups 1 and 3. Plasma and dialysate concentrations of insulin increased during the initial hour and then decreased to the baseline value in groups 1 and 3, while in group 2 it continuously increased. Significantly lower sieving coefficients for glucose in the high glucose and high insulin group suggest that transport mechanisms other than simple passive transport are involved in peritoneal glucose transport, and that high glucose per se and/or high insulin may be important factors that determine glucose transport characteristics.

Effect of blood perfusion on diffusive transport in peritoneal dialysis

Diffusive transport between blood and dialysate during peritoneal dialysis is evaluated in clinical and experimental studies by the diffusive mass transport coefficient, KBD. This global parameter depends on the local diffusive characteristics of the blood capillary wall (permeability) and the tissue, as well as on the density and distribution of capillaries within the tissue. It also depends on the rate of delivery (or washout) of solutes from the tissue with blood flow, that is, on the rate of tissue perfusion. However, the role of blood perfusion in peritoneal transport has not been theoretically evaluated. The relationship between the local characteristics of the peritoneal tissue and the global diffusive mass transport coefficient was studied using a new extended version of the distributed model for peritoneal transport, which included the effect of tissue perfusion and capillary surface area on the blood-tissue transport. The solute concentration profiles within the tissue were found to depend on the solute penetration depth, which is equal to the square root of the ratio of the solute diffusivity in tissue to the solute clearance from the capillary bed to tissue. It was shown that KBD might be interpreted as the dialysance of a capillary bed of a characteristic size that would be immersed directly in dialysate. A definition of the effective peritoneal blood flow (EPBF; the blood flow within the tissue layer) was formulated, and it was shown that EPBF depends on the local transport characteristics for the solute. Assuming typical values of the model parameters (known from physiological studies), the values of KBD and EPBF for urea, creatinine, glucose, and CO2 were calculated and compared with the measured values with good qualitative agreement. The transient initial increase of KBD values observed at the beginning of the peritoneal dialysis dwell was interpreted as a transient sixfold increase in tissue perfusion and a twofold increase in the capillary surface area. The distributed model can be useful as a theoretical tool for detailed physiological interpretations of changes in peritoneal transport associated with changes in peritoneal microcirculation and structure of the interstitium.

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.

The Effects of Ouabain and Potassium on Peritoneal Fluid and Solute Transport Characteristics

We reported anomalous transport characteristics of potassium during experimental peritoneal dialysis in rats and suggested that mechanisms of peritoneal potassium transport could be other than simple passive transport. Intracellular transport of potassium in cultured human mesothelial cells was reported to be regulated by three different pathways, such as channels blocked by ouabain, channels blocked by furosemide, and other. To investigate the effect of ouabain on peritoneal potassium and water transport characteristics. A single 4-hour peritoneal dwell was performed in 28 Sprague-Dawley rats. To minimize the diffusive transport of potassium, 4.5 mmol/L of KCl was added into conventional dialysis solution with 3.86% glucose [acidic peritoneal dialysis solution (APD)]. To evaluate the effect of the pH of dialysis solution on the transport of potassium and water, 4 mmol/L of NaOH was added into the potassium-containing study solutions [neutral peritoneal dialysis solution (NPD)]. To evaluate the effect of a potassium channel blocker on peritoneal potassium transport ATPase sensitive Na+-K+-transport inhibitor, ouabain (10(-5) mmol/L) was added to dialysis solutions immediately before the dwell study in eight rats with APD (APD-O) and six rats with NPD (NPD-O). Ouabain was not added in eight and six rats with APD and NPD (APD-C and NPD-C, respectively). They were used as control. Infusion volume was 30 mL. The intraperitoneal volume (V(D)) was estimated by using a volume marker dilution method with corrections for the elimination of volume marker, radioiodinated human serum albumin (RISA), from the peritoneal cavity (K(E)). The diffusive mass transport coefficient (K(BD)) and sieving coefficient (S) were estimated using the modified Babb-Randerson-Farrell model. V(D) was significantly higher (p < 0.05 from 90 min to 240 min) and K(E) (0.027+/-0.018 mL/min for APD-O, 0.026+/-0.017 mL/min for NPD-O, and 0.030+/-0.022 mL/min for NPD-C, vs 0.058+/-0.030 mL/min for APD-C, p < 0.05 for each) significantly lower during dialysis with APD-O, NPD-O, and NPD-C than with APD-C. The intraperitoneal glucose expressed as a percentage of the initial amount was significantly higher with APD-O, NPD-C, and NPD-O than with APD-C (p < 0.05 from 90 min to 240 min). K(BD) for sodium was higher during dialysis with ouabain than without ouabain, while K(BD) for urea, glucose, and potassium, and S for urea, glucose, sodium, and potassium did not differ between the four groups. The physiologic potassium concentration in neutral dialysis solutions and the use of ouabain decreased the intraperitoneal fluid absorption. The diffusive transport coefficient and sieving coefficient for potassium did not differ, while the diffusive transport coefficient for sodium increased during use of ouabain.

Peritoneal Fluid and Solute Transport with Different Polyglucose Formulations

To study peritoneal fluid and solute transport characteristics using different polyglucose solutions with and without the addition of glucose. Thirty-one rats were divided into three groups. A 4-hour dwell study with frequent dialysate and blood samples was performed in each rat using 25 mL of 7.5% polyglucose solution (PG, n = 11), 7.5% polyglucose + 0.35% glucose solution (PG1, n = 12), or 3.75% polyglucose + 1.93% glucose solution (PG2, n = 8). Radiolabeled human albumin (RISA) was added to the solutions as an intraperitoneal volume (i.p.V) marker. In addition, polyglucose degradation was evaluated ex vivo over 24 hours. Thirty-one male Sprague-Dawley rats (300 g) were used. Fluid and solute (glucose, urea, sodium, potassium, and total protein) transport characteristics as well as changes in dialysate osmolality were evaluated. The i.p.V was higher in the PG1 and PG2 groups than in the PG group during the first 2 hours of the dwell. The i.p.V, in fact, decreased during the first hour of the dwell in the PG group. However, the net ultrafiltration at 4 hours tended to be lower in the PG2 (3.2 +/- 1.5 mL) group compared to the PG (5.1 +/- 2.3 mL) and the PG1 groups (5.2 +/- 2.1 mL) (p = 0.07), and no significant difference was found between the PG and PG1 groups. Adding glucose to the PG solution increased the RISA elimination rate (KE, representing the fluid absorption rate from the peritoneal cavity): 25.5 +/- 8.2, 37.5 +/- 12.2, and 42.5 +/- 8.9 microL/min for the PG, PG1, and the PG2 group, respectively, p < 0.01. Dialysate osmolality (D[OS]) increased with the dwell time in the PG and PG1 groups but decreased in the PG2 group.The increase in D(OS) was partially due to the degradation of glucose polymer, which was supported by the marked increase in osmolality over 24 hours of incubation of PG solution with peritoneal fluid, ex vivo. The diffusive mass transport coefficient for the investigated solutes did not differ among the three groups (except for glucose, which was significantly lower in the PG group). The sieving coefficient for sodium was significantly higher in the PG group compared to the PG1 group (p < 0.05). Our results suggest that, although there was an initial decrease in the intraperitoneal dialysate volume, significant amounts of fluid can be removed by polyglucose solution during a single 4-hour dwell in rats, despite the low osmolality of the solution. The positive fluid removal induced by the PG solution is partially due to the lower fluid absorption rate associated with this solution and may, to some extent, also be due to the degradation of glucose polymer within the peritoneal cavity, resulting in increased dialysate osmolality. The addition of glucose to the polyglucose solution does not seem to improve ultrafiltration in a 4-hour dwell in the rat model. However, the peritoneal fluid absorption rate may be increased, and peritoneal transport of glucose and sodium may be altered, by adding glucose to the polyglucose solution.

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.

A quantitative analysis of sodium transport and removal during peritoneal dialysis

To quantitatively evaluate peritoneal sodium transport, the diffusive mass transport coefficient (KBD) and sieving coefficient (S), as well as the mass of sodium transported by diffusion (DM), by convection (CM) and by fluid absorption (AM) and the total sodium mass removed (RM) were calculated during a series of single dwell studies in CAPD patients. A six-hour dwell study was performed in 68 patients using 2 liter of 1.36% (N = 13), 2.27% (N = 9) or 3.86% (N = 46) glucose dialysis fluid with 131I-albumin as the intraperitoneal volume marker. The patients in whom the 3.86% glucose dialysis fluid was applied were further divided into four transport groups according to a modified peritoneal equilibration test: high (H), high-average (H-A), low-average (L-A), and low (L) transport. There was no significant difference in KBD nor in S for sodium among different solutions. However, the removed sodium mass (RM) was significantly higher in the 3.86% (70.5 +/- 31.5 mmol) and 2.27% (36.0 +/- 21.0 mmol) solutions as compared to that of the 1.36% (-1.8 +/- 26 mmol) solution mainly due to increased both CM and DM. In general, CM was twice as high as DM. AM substantially decreased sodium removal. Among the different transport groups, the KBD and S values for sodium were significantly higher in the H group as compared to the other transport groups (both P < 0.05). However, RM was significantly lower in the H group mainly due to higher AM. Using a 3.86% glucose solution, the D/P for sodium was found to be significantly different (but only after 120 min of the dwell) between all the different transport groups. In conclusion, sodium removal in CAPD is strongly related to the fluid removal. The ultrafiltration induced convective transport (CM) and peritoneal absorption of sodium (AM) were of similar magnitude and were twice as high as the diffusive transport (DM) and both play an important role in the peritoneal sodium balance. A D/P for sodium using the 3.86% glucose solution, especially at the end of the dwell, can be used to discriminate between different transport categories of patients. High transport patients have a poor fluid and sodium removal that are likely to affect their clinical outcome.

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.