Peritoneal Fluid Absorption Rate Research Articles

Role of diaphragmatic, visceral, and parietal pathways in peritoneal fluid absorption in rat peritoneal dialysis.

Assessment was made of the contribution of lymphatic and nonlymphatic fluid absorption to net fluid loss from the peritoneal cavity. Diaphragmatic, visceral, and parietal pathways in lymphatics and nonlymphatics were examined using a rat model with adhesion of the diaphragm to the liver, evisceration, these two procedures in combination, and without treatment. In each of these cases, six rats were used, each dialyzed for 180 min with Krebs-Ringer solution. The peritoneal net fluid absorption rate (PNFAR) was determined based on the disappearance of 125I-bovine serum albumin (BSA) from the peritoneal cavity and the lymphatic absorption rate (LAR), was based on the appearance of this albumin in the blood. Seventy-eight percent of net fluid loss occurred via the nonlymphatic pathway, primarily through parietal and visceral absorption; and the remaining 22% through the lymphatics, the main pathway being the subdiaphragmatic lymphatics. Nonlymphatic fluid absorption would thus appear to be a major route of fluid loss from the peritoneal cavity in rat peritoneal dialysis.

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.

Threefold Peritoneal Test of Osmotic Conductance, Ultrafiltration Efficiency, and Fluid Absorption

Fluid removal during peritoneal dialysis depends on modifiable factors such as tonicity of dialysis fluids and intrinsic characteristics of the peritoneal transport barrier and the osmotic agent-for example, osmotic conductance, ultrafiltration efficiency, and peritoneal fluid absorption. The latter parameters cannot be derived from tests of the small-solute transport rate. We here propose a simple test that may provide information about those parameters. Volumes and glucose concentrations of drained dialysate obtained with 3 different combinations of glucose-based dialysis fluid (3 exchanges of 1.36% glucose during the day and 1 overnight exchange of either 1.36%, 2.27%, or 3.86% glucose) were measured in 83 continuous ambulatory peritoneal dialysis (CAPD) patients. Linear regression analyses of daily net ultrafiltration in relation to the average dialysate-to-plasma concentration gradient of glucose allowed for an estimation of the osmotic conductance of glucose and the peritoneal fluid absorption rate, and net ultrafiltration in relation to glucose absorption allowed for an estimation of the ultrafiltration effectiveness of glucose. The osmotic conductance of glucose was 0.067 ± 0.042 (milliliters per minute divided by millimoles per milliliter), the ultrafiltration effectiveness of glucose was 16.77 ± 7.97 mL/g of absorbed glucose, and the peritoneal fluid absorption rate was 0.94 ± 0.97 mL/min (if estimated concomitantly with osmotic conductance) or 0.93 ± 0.75 mL/min (if estimated concomitantly with ultrafiltration effectiveness). These fluid transport parameters were independent of small-solute transport characteristics, but proportional to total body water estimated by bioimpedance. By varying the glucose concentration in 1 of 4 daily exchanges, osmotic conductance, ultrafiltration efficiency, and peritoneal fluid absorption could be estimated in CAPD patients, yielding transport parameter values that were similar to those obtained by other, more sophisticated, methods.

Short-term effects of bicarbonate/lactate-buffered and conventional lactate-buffered dialysis solutions on peritoneal ultrafiltration: a comparative crossover study

This study was designed to compare the effects of a conventional lactate-based peritoneal dialysis (PD) solution (D) and a new biocompatible bicarbonate/lactate-based solution with a low concentration of glucose degradation products (P) on peritoneal ultrafiltration (UF) and other peritoneal membrane indices. Twenty-six stable, prevalent PD patients were enrolled in this prospective study. They sequentially underwent 3 months of therapy with the D solution and 3 months with the P solution in a randomized order. Daily, overnight and 4-h UF on PET were measured and other peritoneal membrane indices were also assessed using PET with 2.27% glucose solution. Twenty-one patients successfully completed the study. The mean daily peritoneal UF with D was 1324 +/- 602 ml and 881 +/- 633 ml with P (P < 0.001) and this lower daily UF of 443 ml (95% CI 275-610 ml) with P was associated with a similarly lower daily total fluid removal of 394 ml (95% CI 210-577 ml), as urine volume did not differ between D and P. The decrement in UF with the P solution was reversible. There were no significant differences in other peritoneal membrane indices (D/P creatinine, D/D0 glucose, 4-h UF at PET, weekly creatinine clearance, weekly urea Kt/V) or blood pressure and body weight between the solutions whereas calculated peritoneal fluid absorption rate was significantly higher with the P than with the D solution. This study shows that the daily UF with the P solution may be lower than with the D solution. The mechanism for this short-term and reversible effect that conceivably reflects differences in biocompatibility is not clear although our results implicate that the peritoneal fluid absorption rate may differ between the two solutions.

Increased Dialysate Levels of Phospholipids Containing Unsaturated Fatty Acid Are Associated with Increased Peritoneal Transport Rate

High peritoneal transport status in end-stage renal disease patients receiving peritoneal dialysis was shown to be associated with increased morbidity and mortality. Although the pathogenesis of increased peritoneal transport is still not clear, previous studies have demonstrated that phospholipids (PLs) are present on the peritoneal mesothelium and when added to dialysate can decrease the peritoneal fluid absorption rate and increase peritoneal fluid removal. In the present report, we explored the relationship between peritoneal transport and dialysate loss of endogenous PLs.We evaluated 48 prevalent continuous ambulatory peritoneal dialysis patients with high or low peritoneal transport in a cross-sectional study. The 4-hour dwell dialysate PL profile was analyzed by high-performance liquid chromatography coupled with electrospray ionization ion trap mass spectrometry. The patients' peritoneal small solute transport rate was assessed by D/P(Cr) at 4 h and their fluid transport by kinetic modeling.While there were no significant differences between the 2 groups in age, sex, diabetic status and time on dialysis, high transporters had a significantly higher D/P(Cr) and peritoneal fluid absorption rate (K(e)) than low transporters. The PLs in dialysate effluents mainly consisted of PLs containing unsaturated fatty acid, and the concentrations, as well as the amount, of PLs were significantly elevated in the dialysate of high transporters as compared to low transporters.Our results showed that dialysate from high transporters exhibited elevated levels of PLs, especially PLs containing unsaturated fatty acid, suggesting a possible loss of peritoneal surface-active PLs in peritoneal dialysis, and this loss may contribute to the alteration in peritoneal transport.

Association between Arterial Stiffness and Peritoneal Fluid Kinetics

Background: A high peritoneal transport status in continuous ambulatory peritoneal dialysis (CAPD) patients is associated with a markedly increased morbidity and mortality. While the causes are as yet unknown, overall the proportion of deaths due to cardiovascular disease is estimated at 40–50% among dialysis patients. Arterial stiffness has been established as a cardiovascular risk factor, while the links between peritoneal transport status and aortic stiffness have not yet been investigated. Methods: We included 65 prevalent CAPD patients (24 males/41 females) from our center in a cross-sectional study. Arterial stiffness was assessed by brachial pulse pressure (PP) and carotid-femoral pulse wave velocity (C-F PWV). The patients’ peritoneal fluid transport was assessed by kinetic modeling. The patients’ peritoneal small solute transport rate was assessed by D/P_cr at 4 h. Extracellular water to total body water (E/T) ratio was assessed by means of bioimpedance analysis. C-reactive protein was also measured. Results: C-F PWV was positively correlated with patients’ age (r = 0.489, p < 0.01), diabetic status (r = 0.327, p < 0.01), peritoneal fluid absorption rate (Ke; r = 0.251, p < 0.05), PP (r = 0.483, p < 0.01), and E/T (r = 0.517, p < 0.01). Multivariate regression analysis showed that C-F PWV was independently related to E/T (p < 0.01), PP (p < 0.01), age (p < 0.05), and Ke (p < 0.05). Conclusion: Peritoneal fluid transport (Ke), as well as E/T, age and PP were found to be independent predictors of elevated C-F PWV in CAPD patients, suggesting that there might be a link between high aortic stiffness and increased Ke rate, hypothetically through generalized vasculopathy.

Effects of Peritoneal Resting on Peritoneal Fluid Transport Kinetics

Peritoneal resting has been used to restore peritoneal ultrafiltration capacity in peritoneal dialysis patients. Therefore, in the present study, we made a detailed investigation on the effects of peritoneal resting on peritoneal fluid transport characteristics in patients on continuous ambulatory peritoneal dialysis (CAPD). A temporary transfer to daytime ambulatory peritoneal dialysis with a nocturnal "empty belly" was applied to let the peritoneal membrane rest overnight in patients with poor ultrafiltration capacity. All included patients were asked to record appropriately their dialysis exchanges for the assessment of peritoneal fluid transport characteristics, which were evaluated before and after peritoneal resting. Seven CAPD patients were included in the present study. There was a significant improvement in peritoneal ultrafiltration capacity as assessed by ultrafiltration volume per gram of glucose load. Patients' daily glucose exposure and dialysate-to-plasma ratio of creatinine were significantly decreased after peritoneal resting. The peritoneal fluid absorption rate was also significantly decreased after peritoneal resting: 1.011 +/- 0.4484 versus 0.625 +/- 0.3833 mL/minute. The present study suggests that peritoneal resting can improve CAPD patients' ultrafiltration capacity and decrease the use of hypertonic dialysis solution. The improved ultrafiltration capacity by peritoneal resting was due to decreased membrane solute transport rate and decreased peritoneal fluid absorption rate.

Ultrafiltration Capacity and Peritoneal Fluid Kinetics in Continuous Ambulatory Peritoneal Dialysis Patients

Volume control is critical for peritoneal dialysis. Although peritoneal equilibration test (PET) has been used to clarify the peritoneal membrane characteristics, it is not able to adequately predict peritoneal fluid removal and optimize appropriately the dwell time. In the present study, we applied computer simulation and performed a more detailed evaluation of the fluid kinetics in patients with different ultrafiltration (UF) capacity. Patients who used three to four exchanges of 2.27% glucose dialysate per day (poor UF capacity group), and patients who used three to four exchanges of 1.36% glucose dialysate per day (good UF capacity group) to achieve adequate amount of peritoneal fluid removal were included in the present analysis. All included patients were asked to record appropriately their dialysis exchanges for the assessment of their peritoneal fluid transport characteristics. Seventeen continuous ambulatory peritoneal dialysis patients were selected in the present study, nine in poor UF capacity group and eight in good UF capacity group. Patients in poor UF capacity group had significantly higher daily glucose exposure, higher dialysate-to-plasma ratio of creatinine (D/P creatinine) values, and higher peritoneal fluid absorption rate, K(e), as compared to patients with good UF capacity. Our results suggest that patients with poor UF capacity have significant higher peritoneal small solute transport rate, and more importantly, higher peritoneal fluid absorption rate as compared to patients with good UF capacity.

Intelligent predicting approach of peritoneal fluid absorption rate based-on neural network

This paper addresses the important intelligent predicting problem of peritoneal absorption rate in the peritoneal dialysis treatment process of renal failure. As the index of dialysis adequacy, KT/V and Ccr are widely used and accepted. However, growing evidence suggests that the fluid balance may play a critical role in dialysis adequacy and patient outcome. Peritoneal fluid absorption decreases the peritoneal fluid removal. Understanding the peritoneal fluid absorption rate will help clinicians to optimize the dialysis dwell time. The neural network approach is applied to the prediction of peritoneal absorption rate. Compared with multivariable regression method, the experimental results showed that neural network method has an advantage over multivariable regression. The application of this predicting method based-on neural network in clinic is instructive.

Increased Peritoneal Membrane Permeability is Associated with Abnormal Peritoneal Surface Layer

We recently showed that the peritoneal surface layer may be an important barrier in modulating peritoneal membrane permeability. In the present study, we investigated the relationship between an increased peritoneal transport rate and the peritoneal surface layer. Male Sprague-Dawley rats (n = 8) received intraperitoneal injections of 4.25% glucose dialysate daily for 1 week. Forty-eight hours after the last injection, a 4-hour dwell study using 25 mL 4.25% glucose dialysate was performed in each rat. The results were compared with those from control rats that received no intraperitoneal injections (n = 8). The peritoneal fluid and small-solute transport characteristics were evaluated. The peritoneal surface layer was studied using an electron microscope. The phospholipids content of the dialysate was also evaluated. Peritoneal fluid removal was significantly reduced in the daily injection group (30.6 +/- 1.3 mL) as compared with the control group (38.2 +/- 0.6 mL). The peritoneal fluid absorption rate and small-solute transport rate were also significantly higher in the daily injection group as compared with the control group. The amounts of phospholipids in the dialysate were significantly lower in the daily injection group--especially the quantity of phosphatidylcholine. However, lysophosphatidylcholine increased significantly in the daily injection group. Electron microscopy showed that the peritoneal surface layer was almost completely gone in the daily injection group, but that a dense and thick (average 4 microm) peritoneal surface layer was present on the top of the mesothelial cells in the control group. Our results suggest that daily injection of hypertonic glucose dialysate significantly increased the peritoneal transport rate. The increased peritoneal transport rate was associated with a significant reduction in the peritoneal surface layer and the phospholipids content of the dialysis effluent.

Errors Involved in the Application of an Imperfect Peritoneal Volume Marker

Peritoneal volume markers have been used in numerous studies on fluid transport in peritoneal dialysis. The basic assumption used was that the macromolecular marker was stable and that the free fraction of a label (usually radiolabel) was negligibly small. In this study are presented theoretical investigations on the errors involved in application of an imperfect volume marker containing free fraction of a label. These investigations were used in assessing the errors in calculation of peritoneal volume time course, V, and fluid absorption rate (estimated by volume marker clearance, kE) using data from 20 clinical dwell studies with 1.36% Dianeal dialysis solution and radioiodinated human serum albumin as a volume marker. It has been shown that with an in vitro measured 125I free fraction of 2.72%, the error of kE estimation was 11%. However, the maximal error in estimation of V was only 0.2%. In conclusion, the performed analysis implies that calculation of the peritoneal volume time course during the dwell (with correction for the volume marker elimination) is very reliable, and the existence of a free fraction of a volume marker label results in a negligibly small error. However, even small free fraction of the label results in a significant overestimation of the fluid absorption rate.

Structural and Functional Alterations of the Peritoneum after Prolonged Exposure to Dialysis Solutions: Role of Aminoguanidine

The effect of long-term use of high glucose dialysate on peritoneal structure and function, and its relation with accumulation of advanced glycosylation end-product (AGE) in the peritoneum was investigated in this study. Dialysates with 4.25% glucose were injected into the peritoneal cavity of normal rats for 12 weeks without (PD, n = 7) and with (1 g/L, PD+AG, n = 7) aminoguanidine in their drinking water. Rats not having intraperitoneal (IP) injection served as control (n = 9). After 12 weeks of IP injection, a 2-hour peritoneal equilibration test (PET) was performed using 30 mL 4.25% glucose dialysate. Intraperitoneal volume (IPV), dialysate-to-plasma urea ratio at 2 hours (D/P2), the ratio of dialysate glucose at 2 hours to initial dialysate glucose (D2/D0), and the peritoneal fluid absorption rate (Qa) were evaluated. After the PET, samples of the parietal peritoneum were taken for hematoxylin and eosin (H&E) staining and immunohistochemical staining for AGE. The IPV and D2/D0 glucose were significantly lower and Qa and D2/P2 urea significantly higher in the PD group than in the control group. Aminoguanidine reversed in part the changes in IPV and D2/P2 urea in the PD group; it had no effect on Qa and D2/D0 glucose. The H&E staining showed a linear mesothelial lining with negligible cells and capillaries in the narrow submesothelial space in the control group. Mesothelial denudation and submesothelial infiltration of monocytes and capillary formation were observed in the PD group. Mesothelial denudation was relatively intact in the PD+AG group compared with the PD group. Submesothelial monocyte infiltration and capillary formation in the PD+AG group were not as prominent as in the PD group. Positive AGE staining was found in the submesothelial space, vascular walls, and endomysium in the PD group, while it was markedly attenuated in PD+AG group and negligible in the control group. Long-term use of high glucose solutions induced peritoneal AGE accumulation and mesothelial denudation, and increased peritoneal permeability and peritoneal fluid absorption rate. Inhibition of peritoneal AGE accumulation prevented those functional and structural damages to the peritoneum.

Hyaluronan Preserves Peritoneal Membrane Transport Properties

We have shown that intraperitoneal (i.p.) addition of hyaluronan (HA) in a single dwell study in rat could increase peritoneal fluid removal by decreasing the peritoneal fluid absorption rate. In this study, we investigated the impact of repeated use of HA on peritoneal membrane transport characteristics. Twelve male Sprague-Dawley rats received a once-daily i.p. injection of 25 mL 4.25% glucose dialysis solution without (HP group, n = 6) or with 0.025% HA (HA group, n = 6) for 1 week. Forty-eight hours after the last injection, a 4-hour dwell using 25 mL 4.25% glucose dialysis solution with i.p. volume marker and frequent dialysate and blood samplings was performed in each rat as well as in rats that did not receive any injection (control group, n = 8). Although the i.p. volumes were significantly lower in the HP and HA groups compared to the control group, i.p. volume in the HA group was significantly higher than in the HP group. Net ultrafiltration at 4 hours was 5.6 +/- 1.3 mL, 10.2 +/- 1.8 mL, and 13.2 +/- 0.6 mL for the HP, HA, and control group, respectively. The peritoneal fluid absorption rate decreased by 45% in the HA group compared to the HP group. There was no significant difference in peritoneal fluid absorption rate between the HA and the control group. No difference was found in the direct lymphatic absorption rate between the HP and HA groups [0.010 +/- 0.003 mL/minute in the HP group and 0.011 +/- 0.004 mL/min in the HA group] although they were both higher than that of the control group (0.004 +/- 0.001 mL/min). The solute transport rates were in general significantly higher in the HP group compared to the HA and control groups, and there was no significant difference between the latter two groups, except that protein transport rate was significantly lower in the HA group compared to the control group. The present study suggests that (1) repeated exposure to hypertonic glucose-based dialysis solution results in increased peritoneal solute transport rates, as well as increased peritoneal fluid absorption rates; and (2) these changes, reflecting a highly permeable peritoneal membrane, were ameliorated by repeated i.p. addition of hyaluronan. The similar changes in the direct lymphatic absorption rate in rats that received daily i.p. injection of dialysis solution suggest that direct peritoneal lymphatic absorption was not influenced by hyaluronan.

Fluid and Solute Transport using Different Sodium Concentrations in Peritoneal Dialysis Solutions

Fluid and sodium balance is important for the success of long-term peritoneal dialysis. Convective transport is the major determinant for sodium removal during peritoneal dialysis using conventional dialysis solutions. However, recent studies showed that lower sodium concentration in dialysate could significantly increase sodium removal by increasing the diffusion gradient, thereby increasing diffusive transport. In the present study, we investigated the influence of the sodium concentration gradient on the diffusive transport coefficient, K(BD) for sodium. A 4-hour dwell study was done in Sprague-Dawley rats using 25 mL 5% glucose (NS), 5% glucose + 0.3% NaCl (LS), 5% glucose + 0.6% NaCl (MS), or 5% glucose + 0.9% NaCl (HS), with frequent dialysate and blood sampling. Radiolabeled human albumin (RISA) was added to the solution as an intraperitoneal volume marker. The peritoneal fluid and sodium transport characteristics were evaluated. Significant ultrafiltration (both net ultrafiltration and transcapillary ultrafiltration) was observed in each group despite the osmolality of the 5% glucose solution being slightly lower than the plasma osmolality. There was no difference in peritoneal fluid absorption rate and direct lymphatic absorption among the four groups. With the sieving coefficient for sodium set to 0.55, a significantly higher K(BD) for sodium was found in the NS compared to the HS group. The K(BD) for sodium was 0.21+/-0.01, 0.20+/-0.01, 0.17+/-0.01, and 0.09+/-0.01 mL/min for the NS, LS, MS, and HS groups, respectively. The K(BD) values for glucose were significantly lower in the NS and LS groups compared to the MS and HS groups. Our results suggest that (1) sodium concentration may affect peritoneal sodium K(BD)--as the sodium concentration gradient increased, the K(BD) decreased; (2) 5% glucose solution could induce significant peritoneal ultrafiltration in normal rats despite its initial hypo-osmotic nature, this was due to the significantly lower glucose transport rate than sodium transport rate; and (3) a lower dialysate sodium concentration may decrease peritoneal glucose absorption.

Effect of peritonitis on peritoneal transport characteristics: Glucose solution versus polyglucose solution

Peritonitis is a common clinical problem and contributes to the high rate of technique failure in continuous ambulatory peritoneal dialysis treatment. The present study investigated the effect of peritonitis on peritoneal fluid and solute transport characteristics using glucose and polyglucose (icodextrin) solutions. A four-hour dwell was performed in 32 Sprague-Dawley rats (8 rats in each group), with 131I albumin as an intraperitoneal volume marker. Peritonitis was induced by an intraperitoneal injection of 2 mL lipopolysaccharide (100 microg/mL phosphate-buffered saline) four hours before the dwell. Each rat was intraperitoneally infused with 25 mL of 3.86% glucose [glucose solution control group (Gcon) and glucose solution peritonitis group (Gpts)] or 7.5% icodextrin solution [icodextrin solution control group (Pgcon) and icodextrin peritonitis group (PGpts)]. Net ultrafiltration was significantly lower (by 44%) in the Gpts as compared with the Gcon group, but was significantly higher (by 138%) in the PGpts as compared with the PGcon group. The peritoneal fluid absorption rate, including the direct lymphatic absorption rate, was significantly increased (by 78%) in the Gpts group as compared with the Gcon group. However, the total fluid absorption did not differ between the PGpts and the PGcon groups. The dialysate osmolality decreased much faster in the Gpts group as compared with the Gcon group, resulting in significantly lower (by 9%) transcapillary ultrafiltration in the Gpts group. In contrast, the dialysate osmolality increased faster in the PGpts group as compared with the PGcon group, resulting in higher (by 40%) transcapillary ultrafiltration in the PGpts group. The in vitro increase in dialysate osmolality was also higher in the PGpts group as compared with the PGcon group. The solute diffusive transport rates were, in general, increased in the two peritonitis groups as compared with their respective control groups. Our results suggest the following: (1) Peritonitis results in decreased net ultrafiltration using glucose solution caused by (a) decreased transcapillary ultrafiltration and (b) increased peritoneal fluid absorption. (2) Ultrafiltration induced by the icodextrin solution appears to be related to the increase in dialysate osmolality (mainly because of the degradation of icodextrin). (3) Peritonitis results in increased degradation of icodextrin and a faster increase in dialysate osmolality and therefore better ultrafiltration, whereas the fluid absorption rate does not change. (4) Peritonitis results in increased peritoneal diffusive permeability.

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.

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.

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.

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.

Physiological Saline is not a Biocompatible Peritoneal Dialysis Solution

We have previously demonstrated that daily exposure to dialysis fluid results in significantly increased peritoneal lymphatic flow. In this study, we investigated if daily intraperitoneal infusion of saline (isotonic, glucose free) could cause similar changes. Sixteen male SD rats received daily infusion (i.p.) of 20 ml saline for ten days (Saline group). Twenty-four hours after the last infusion, a 4 hour dwell study using 25 ml 3.86% glucose dialysis solution with frequent dialysate and blood sampling was done in each rat as well as in rats which did not receive daily infusion (Control, n=8). Radiolabeled human albumin (RISA) was added to the solution as an intraperitoneal volume marker. Radioactivity, glucose, urea, sodium, and potassium were measured for each sample. In a separate study, the RISA absorption to peritoneal tissue was also determined. The net ultrafiltration was significantly decreased in the daily infusion group (p<0.05). However, the apparent volume at 3 minutes of the dwell was markedly increased; this was due to a significant increase in the RISA binding (1.5-12.0% in the Saline group vs. 0.45-1.12% in the Control group) to peritoneal tissues as assessed by measurement of RISA recovery at 3 min of the dwell. This resulted in a significant overestimation both of the intraperitoneal volume (IPV) at 3 min and the (apparent) fluid absorption rate (as estimated by the transport of RISA out of peritoneal cavity): 0.087+/-0.026 ml/min in the Saline group vs. 0.052+/-0.007 ml/min in the Control group, p<0.001. The direct lymphatic flow as estimated by the clearance of RISA to plasma (which should not be affected by the RISA binding) also increased markedly (0.021+/-0.005 ml/min in the Saline group vs. 0.008+/-0.001 ml/min in the control group). There was no significant difference in the D/P values for small solutes (urea, sodium, potassium, urate) and D/D0 for glucose between the two groups. 1) Daily infusion of physiological saline into peritoneal cavity may increase the peritoneal lymphatic flow; 2) The significant (apparent) increase in IPV shortly after infusion may suggest increased RISA binding to peritoneal tissues (which may be related to the damage of the tissues, and results in overestimation of the peritoneal fluid absorption rate); 3) Saline is not a biocompatible peritoneal dialysis solution, and should therefore not be used as a control or flush solution.