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Water removal which is a key treatment goal of automated peritoneal dialysis (APD) can be assessed cycle-by-cycle using remote patient monitoring (RPM). We analysed ultrafiltration patterns during night APD following a dry day (APDDD; no daytime fluid exchange) or wet day (APDWD; daytime exchange). Ultrafiltration for each APD exchange were recorded for 16 days using RPM in 14 patients. The distributed model of fluid and solute transport was applied to simulate APD and to explore the impact of changes in peritoneal tissue hydration on ultrafiltration. We found lower ultrafiltration (mL, median [first quartile, third quartile]) during first and second vs. consecutive exchanges in APDDD (−61 [−148, 27], 170 [78, 228] vs. 213 [126, 275] mL; p WD (81 [−8, 176], 81 [−4, 192] vs. 115 [4, 219] mL; NS). Simulations in a virtual patient showed that lower ultrafiltration (by 114 mL) was related to increased peritoneal tissue hydration caused by inflow of 187 mL of water during the first APDDD exchange. The observed phenomenon of lower ultrafiltration during initial exchanges of dialysis fluid in patients undergoing APDDD appears to be due to water inflow into the peritoneal tissue, re-establishing a state of increased hydration typical for peritoneal dialysis.

Lay summary Peritoneal dialysis (PD) uses the peritoneal membrane for dialysis. The peritoneal membrane is a thin layer of tissue that lines the abdomen. The lining is used as a filter to help remove extra fluid and poisonous waste from the blood. Everybody is unique. What is normal for one person’s membrane may be very different from another person’s. The kidney care team wants to provide each person with the best dialysis prescription for them and to do this they must evaluate the person’s peritoneal lining. Sometimes dialysis treatment itself can cause the membrane to change after some years. This means more assessments (evaluations) will be needed to determine whether the person’s peritoneal membrane has changed. Changes in the membrane may require changes to the dialysis prescription. This is needed to achieve the best dialysis outcomes. A key tool for these assessments is the peritoneal equilibration test (PET). It is a simple, standardized and reproducible tool. This tool is used to measure the peritoneal function soon after the start of dialysis. The goal is to understand how well the peritoneal membrane works at the start of dialysis. Later on in treatment, the PET helps to monitor changes in peritoneal function. If there are changes between assessments causing problems, the PET data may explain the cause of the dysfunction. This may be used to change the dialysis prescription to achieve the best outcomes. The most common problem with the peritoneal membrane occurs when fluid is not removed as well as it should be. This happens when toxins (poisons) in the blood cross the membrane more quickly than they should. This is referred to as a fast peritoneal solute transfer rate (PSTR). Since more efficient fluid removal is associated with better outcomes, developing a personal PD prescription based on the person’s PSTR is critically important. A less common problem happens when the membrane fails to work properly (also called membrane dysfunction) because the peritoneal membrane is less efficient, either at the start of treatment or developing after some years. If membrane dysfunction gets worse over time, then this is associated with progressive damage, scarring and thickening of the membrane. This problem can be identified through another change of the PET. It is called reduced ‘sodium dip’. Membrane dysfunction of this type is more difficult to treat and has many implications for the individual. If the damage is major, the person may need to stop PD. They would need to begin haemodialysis treatment (also spelled hemodialysis). This is a very important and emotional decision for individuals with kidney failure. Any decision that involves stopping PD therapy or transitioning to haemodialysis therapy should be made jointly between the clinical team, the person on dialysis and a caregiver, if requested. Although evidence is lacking about how often tests should be performed to determine peritoneal function, it seems reasonable to repeat them whenever there is difficulty in removing the amount of fluid necessary for maintaining the health and well-being of the individual. Whether routine evaluation of membrane function is associated with better outcomes has not been studied. Further research is needed to answer this important question as national policies in many parts of the world and the COVID-19 has placed a greater emphasis and new incentives encouraging the greater adoption of home dialysis therapies, especially PD. For Chinese and Spanish Translation of the Lay Summary, see Online Supplement Appendix 1. Key recommendations Guideline 1: A pathophysiological taxonomy: A pathophysiological classification of membrane dysfunction, which provides mechanistic links to functional characteristics, should be used when prescribing individualized dialysis or when planning modality transfer (e.g. to automated peritoneal dialysis (PD) or haemodialysis) in the context of shared and informed decision-making with the person on PD, taking individual circumstances and treatment goals into account. (practice point) Guideline 2a: Identification of fast peritoneal solute transfer rate (PSTR): It is recommended that the PSTR is determined from a 4-h peritoneal equilibration test (PET), using either 2.5%/2.27% or 4.25%/3.86% dextrose/glucose concentration and creatinine as the index solute. (practice point) This should be done early in the course dialysis treatment (between 6 weeks and 12 weeks) (GRADE 1A) and subsequently when clinically indicated. (practice point) Guideline 2b: Clinical implications and mitigation of fast solute transfer: A faster PSTR is associated with lower survival on PD. (GRADE 1A) This risk is in part due to the lower ultrafiltration (UF) and increased net fluid reabsorption that occurs when the PSTR is above the average value. The resulting lower net UF can be avoided by shortening glucose-based exchanges, using a polyglucose solution (icodextrin), and/or prescribing higher glucose concentrations. (GRADE 1A) Compared to glucose, use of icodextrin can translate into improved fluid status and fewer episodes of fluid overload. (GRADE 1A) Use of automated PD and icodextrin may mitigate the mortality risk associated with fast PSTR. (practice point) Guideline 3: Recognizing low UF capacity: This is easy to measure and a valuable screening test. Insufficient UF should be suspected when either (a) the net UF from a 4-h PET is Guideline 4a: Diagnosing intrinsic membrane dysfunction (manifesting as low osmotic conductance to glucose) as a cause of UF insufficiency: When insufficient UF is suspected, the 4-h PET should be supplemented by measurement of the sodium dip at 1 h using a 3.86% glucose/4.25% dextrose exchange for diagnostic purposes. A sodium dip ≤5 mmol/L and/or a sodium sieving ratio ≤0.03 at 1 h indicates UF insufficiency. (GRADE 2B) Guideline 4b: Clinical implications of intrinsic membrane dysfunction (de novo or acquired): in the absence of residual kidney function, this is likely to necessitate the use of hypertonic glucose exchanges and possible transfer to haemodialysis. Acquired membrane injury, especially in the context of prolonged time on treatment, should prompt discussions about the risk of encapsulating peritoneal sclerosis. (practice point) Guideline 5: Additional membrane function tests: measures of peritoneal protein loss, intraperitoneal pressure and more complex tests that estimate osmotic conductance and ‘lymphatic’ reabsorption are not recommended for routine clinical practice but remain valuable research methods. (practice point) Guideline 6: Socioeconomic considerations: When resource constraints prevent the use of routine tests, consideration of membrane function should still be part of the clinical management and may be inferred from the daily UF in response to the prescription. (practice point)

Background and Aims Experimental studies and computational modeling show increased hydration of peritoneal tissue close to peritoneal surface after intraperitoneal (ip) administration of hypertonic dialysis fluid. This overhydration - due to fluid inflow from peritoneal cavity (driven by increased intraperitoneal pressure) and from blood (due to high interstitial concentration of osmotic agent diffusing from the cavity) - may lead to tissue swelling, as observed in experiments and in disturbed physiological conditions. We estimated the degree of swelling using linear poroelastic theory with fluid and solute transport parameters obtained from clinical studies. Method The spatially distributed model of peritoneal transport was extended by equations for tissue deformation and stress derived from linear poroelastic theory. The model describes also fluid and osmotic agent flows across tissue and capillary wall. We assumed that transport and deformation occur across a layer of tissue with initial intact width L0 and deformed width L; the deformation is described as the ratio L/L0. Transport parameters are assumed as average values estimated for intact tissue by Stachowska-Pietka (2019). As tissue stiffness (Lame coefficient) for muscle is not known, we examined stiffness ranging from 110 mmHg (connective tissue; interstitium) to 700 mmHg (solid tumor). We assumed that for initial periods of peritoneal dialysis when osmotic pressure of dialysis fluid is high: 1) osmotic pressure gradient across the capillary wall prevails over the combined Starling forces, 2) spatial profile of osmotic agent concentration in tissue (interstitial fluid) can be approximated by exponential function with the penetration depth ΛS. The model yields an equation for L/L0 to be solved numerically, but an approximated closed formula also works well for typical dialysis conditions. Results The model predicts that swelling of peritoneal tissue depends on factors such as tissue stiffness, tissue width, solute penetration depth, and transport parameters for tissue and capillary wall, and on the forces that induce fluid transport: intraperitoneal pressure and the increment of osmolality of dialysis fluid over plasma osmolality. Examples of L/L0 yielded by the model - with use of glucose 1.36% dialysis fluid and for two levels of ip hydrostatic pressure (Pip) - are shown. In Figure, left panel, for L0 = 1 cm representing human abdominal muscle, and solute diffusional penetration ΛS=ΛD=0.055 cm, or lower, as due to diffusion against fluid flow, ΛS=ΛD/2=0.027 cm, is plotted versus the tissue stiffness; the dialysis fluid with glucose 1.36% is applied (osmolality increment of 60 mmol/L at the beginning of peritoneal dwell, Waniewski et al, 1996) and Pip is 15 mmHg. As stiffness of abdominal and bowel muscles may be expected around 300 mm Hg, swelling might be up to 15%; it decreases with lower ip hydrostatic and osmotic pressures. Hypothetical dialysis at Pip = 0 (isobaric with interstitial fluid) would reduce swelling by factor 2, see Figure, right panel. The depth of osmotic agent penetration into the tissue impacts tissue hydration and swelling, see Figure 1 for L/L0 with twice reduced ΛS. The model and its approximation by the closed formula provide practically the same outcomes for clinical peritoneal dialysis, see Figure 1, but some discrepancy between them may occur for thin tissue, as rat abdominal wall. The approximate formula for L/L0 works well if ΛS is much shorter than L0. Nevertheless, for high degree of swelling a nonlinear theory should be constructed. Conclusion In peritoneal dialysis, exposure of peritoneal tissue to hypertonic dialysis fluid at increased hydrostatic pressure contributes to overhydration and swelling (by 5-15% after fluid infusion) of the tissue. The extent by which this swelling may contribute to changes in peritoneal tissue structure and function warrants further studies.

The transitory change of fluid and solute transport parameters occurring during the initial phase of a peritoneal dialysis dwell is a well-documented phenomenon; however, its physiological interpretation is rather hypothetical and has been disputed. Two different explanations were proposed: (1) the prevailing view—supported by several experimental and clinical studies—is that a vasodilatory effect of dialysis fluid affects the capillary surface area available for dialysis, and (2) a recently presented alternative explanation is that the molecular radius of glucose increases due to the high glucose concentration in fresh dialysis fluid and that this change affects peritoneal transport parameters. The experimental bases for both phenomena are discussed as well as the problem of the accuracy necessary for a satisfactory description of clinical data when the three-pore model of peritoneal transport is applied. We show that the correction for the change of transport parameters with dwell time provides a better fit with clinical data when applying the three-pore model. Our conclusion is in favor of the traditional interpretation namely that the transitory change of transport parameters with dwell time during peritoneal dialysis is primarily due to the vasodilatory effect of dialysis fluids.

Background and Aims Adequate removal of creatinine and phosphate is one of the key objectives in peritoneal dialysis (PD). Whereas the mechanism of creatinine removal is well known, there are gaps in understanding regulation of phosphate removal. Clinical studies show that although the size of both molecules is similar, their removal might behave differently (Badve et al CJASN 2008). Several, but not all, studies have suggested that peritoneal phosphate clearance is larger when using CAPD than APD prescriptions, suggesting the dwell time or duration is an important determinant of phosphate clearance. The aim of the study was to investigate specifically the effect of dwell duration at the level of single PD exchange with different glucose concentrations on peritoneal phosphate clearance. Method A prolonged 8-hour PET was carried out in 32 clinically stable PD patients with each of three glucose-based solutions: 1.36% (G1), 2.27% (G2), and 3.86% (G3) with temporary drainage at 1 and 4 hours of peritoneal dwell. Dialysate and blood samples were taken to measure infused and drained volume and concentration of phosphate and creatinine in dialysate and blood. Clearances were calculated for a single exchange for each solution and for 4-hour (4H) and 8-hour (8H) dwell periods. For each patient, the 4-hour creatinine D/P ratio for G3 was calculated. The clearance ratio, ClR, defined as the ratio of solute clearance for particular solution to its clearance for the G1 solution, was calculated for both solutes and each solution and dwell durations. Results The obtained values of 4H creatinine D/P ratio for G3 solution were 0.67±0.11 (mean±SD). The values of solute clearances per single exchange expressed in mL/min, are presented in table below. Creatinine and phosphate clearances were found to be solution and dwell duration dependent with p Conclusion Phosphate and creatinine clearances were found to be well correlated during a long, 8-hour PET proving similarities in their transport. Interestingly, the dependence of both clearances and ClR on solution glucose concentration suggest that the removal of phosphate as well as creatinine depends on the ultrafiltration induced by glucose concentration in dialysis solution.

Background and Aims The width of the peritoneum (composed mainly of connective tissue and relatively free of vasculature) is increased in patients on peritoneal dialysis compared to healthy subjects. We investigated to what extent increased intraperitoneal (ip) hydrostatic and osmotic pressures following the infusion of dialysis fluid will change hydration status and width of the peritoneum. Method Using linear theory of poroelasticty, clinical data on transport parameters and experimental data on elastic characteristics of the interstitium, the relative change of the width of the poroelastic layer subject to the combined effect of external hydrostatic and effective osmotic pressures (that is, ideal osmotic pressure multiplied by reflection coefficient for osmotic agent) can be described as a function of effective pressure and elastic modulus of the layer: Lmod/L0 = 1/(1-deltaP*/lambda*), where L0 is initial thickness of the tissue, Lmod is modified thickness of the layer, deltaP* is change in effective combined pressure, and lambda* is the elastic modulus of the poroelastic material. The same formula describes also the change in fractional free fluid volume ratio, thetaF. The elastic modulus of the connective tissue was assumed to be 110 mmHg, as measured for the subcutaneous layer of the tip of mouse tail by Swartz et al (J Biomech, 1999), and reflection coefficient for glucose in the interstitium of 0.0035 as estimated by Stachowska-Pietka et al (NDT, 2019) from clinical data for patients on peritoneal dialysis. Results The ip hydrostatic pressure increases by 2-3 mmHg to 15 mmHg at rest depending on infused volume of dialysis fluid (and posture, body weight and location in abdominal cavity), and may increase to 100 mmHg during activities as coughing, whereas the osmotic pressure of glucose 3.86% dialysis fluid is around 400 mmHg above the osmotic pressure of plasma and interstitial fluid (in equilibrium with plasma). However, due to the low reflection coefficient of interstitium, the effective osmotic pressure of dialysis fluid minus the physiological value of interstitial osmotic pressure is only 1.4 mmHg, and is quickly decreasing with dwell time. Therefore, hydrostatic pressure is the dominant factor for interstitial hydration. Assuming ip pressure of 15 mmHg, the stretch of the peritoneum increases its equilibrium width (at 0 mmHg and isotonic interstitial fluid) by 15%. During physical activities peritoneum may transiently thicken even more. Conclusion The peritoneum becomes overhydrated after infusion of dialysis fluid, which increases interstitial hydrostatic pressure; the thickness and fractional free fluid volume of the peritoneum increase by 15% although transiently higher increases may occur following activities that increase intraperitoneal pressure. The mechanical changes in the peritoneum may contribute to the biological changes in cells present there, as fibroblasts and mesothelial cells. The swelling of the peritoneum is in agreement with the increase in the fractional free fluid volume of the intramuscular interstitium behind the peritoneum as reported by Zakaria et al (Am J Physiol Heart Circ Physiol, 1999).

BackgroundUltrafiltration failure (UFF) in peritoneal dialysis (PD) patients is due to altered peritoneal transport properties leading to reduced capacity to remove excess water. Here, with the aim to establish the role of local alterations of the two major transport barriers, peritoneal tissue and capillary wall, we investigate changes in overall peritoneal transport characteristics in UFF patients in relation to corresponding local alterations of peritoneal tissue and capillary wall transport properties.MethodsSix-hour dwell studies using 3.86% glucose solutions and radioisotopically labelled serum albumin added to dialysate as a volume marker were analysed in 31 continuous ambulatory PD patients, 20 with normal ultrafiltration (NUF) and 11 with UFF. For each patient, the physiologically based parameters were evaluated for both transport barriers using the spatially distributed approach based on the individual intraperitoneal profiles of volume and concentrations of glucose, sodium, urea and creatinine.ResultsUFF patients as compared with NUF patients had increased solute diffusivity in both barriers, peritoneal tissue and capillary wall, decreased tissue hydraulic conductivity and increased local lymphatic absorption and functional decrease in the fraction of the ultra-small pores. This resulted in altered distribution of fluid and solutes in the peritoneal tissue, and decreased penetration depths of fluid and solutes into the tissue in UFF patients.ConclusionsMathematical modelling using a spatially distributed approach for the description of clinical data suggests that alterations both in the capillary wall and in the tissue barrier contribute to UFF through their effect on transport and distribution of solutes and fluid within the tissue.

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 hours. We analysed kinetics of peritoneal ultrafiltration in relation to icodextrin and its metabolites for 16-hours dwells with icodextrin. Design, setting, participants, & 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. Osmolality and sodium were measured in dialysate and plasma. In 11 patients, fractional absorption of icodextrin from dialysate, dialysate and plasma amylase, and high and low (Mw

Fluid and solute transport in poroelastic media is studied. Mathematical modeling of such transport is a complicated problem because of the volume change of the specimen due to swelling or shrinking and the transport processes are nonlinearly linked. The tensorial character of the variables adds also substantial complication in both theoretical and experimental investigations. The one-dimensional version of the theory is less complex and may serve as an approximation in some problems, and therefore, a one-dimensional (in space) model of fluid and solute transport through a poroelastic medium with variable volume is developed and analyzed. In order to obtain analytical results, the Lie symmetry method is applied. It is shown that the governing equations of the model admit a non-trivial Lie symmetry, which is used for construction of exact solutions. Some examples of the solutions are discussed in detail.

Background It is typically assumed that within short time-frames, patient-specific peritoneal membrane characteristics are constant and do not depend on the initial fluid tonicity and dwell duration. The aim of this study was to check whether this assumption holds when membrane properties are estimated using the 3-pore model (3PM). Methods Thirty-two stable peritoneal dialysis (PD) patients underwent 3 8-hour peritoneal equilibration tests (PETs) with different glucose-based solutions (1.36%, 2.27%, and 3.86%). Temporary drainage was performed at 1 and 4 hours. Glucose, urea, creatinine, sodium, and phosphate concentrations were measured in dialysate and blood samples. Three-pore model parameters were estimated for each patient and each 8-hour PET separately. In addition, model parameters were estimated using data truncated to the initial 4 hours of peritoneal dwell. Results In all cases, model-estimated parameter values were within previously reported ranges. The peritoneal absorption (PA) and diffusive permeability for all solutes except sodium increased with fluid tonicity, with about 18% increase when switching from glucose 2.27% to 3.86%. Glucose peritoneal reflection coefficient and osmotic conductance (OsmCond), and fraction of hydraulic conductance for ultrasmall pores decreased with fluid tonicity (over 40% when switching from glucose 1.36%). Model fitting to the truncated 4-hour data resulted in little change in the parameters, except for PA, peritoneal hydraulic conductance, and OsmCond, for which higher values for the 4-hour dwell were found. Conclusion Initial fluid tonicity has a substantial impact on the 3PM-estimated characteristics of the peritoneal membrane, whereas the impact of dwell duration was relatively small and possibly influenced by the change in the patient's activity.

Removal of fluid excess from the plasma volume by ultrafiltration during hemodialysis (HD) is balanced by plasma refilling from the interstitium, driven mainly by the increase in plasma oncotic pressure. We calculated the plasma refilling coefficient (Kr, a parameter expressing the ratio of refilling rate to the increase in oncotic pressure) for nine patients, each undergoing two HD sessions differing by pretreatment fluid status and session time (shorter session, SH, 3.5 h, and longer session, LH, 4.5h). Relative blood volume change was measured online, and solute concentrations were measured regularly during the sessions. The volume of body compartments was measured by bioimpedance. The patients were more volume expanded before LH session (higher initial body mass and total body water). Oncotic pressure was similar for both sessions. The refilling rate, despite higher fluid overload in the LH sessions, was similar for both sessions. The final Kr values stabilized on similar levels (SH: 136.6 ± 55.6 ml/mm Hg/h and LH: 150.7 ± 73.6 ml/mm Hg/h) at similar times, notwithstanding the difference in initial fluid overload between the two groups, suggesting that Kr at dry weight is relatively insensitive to the initial fluid status of the patient.

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.

The principles of peritoneal dialysis are based on the physiological processes and their driving forces which permit the exchange of water (by ultrafiltration and fluid absorption) and solutes (by diffusion and convective transport) between the peritoneal microvasculature and the dialysate. In peritoneal dialysis, the peritoneal transport system—mesenchymal cells, interstitium, microvasculature, and lymphatics—is repeatedly exposed to high concentrations of an osmotic agent, and a volume load, leading to increased intraperitoneal hydrostatic and osmotic pressure. This results in immediate as well as long-term structural and functional changes of the peritoneal transport system. Clinical tests supplemented with mathematical modelling have been developed to monitor the quantitative characteristics of the peritoneal transport system, allowing detection and diagnosis of various problems and guidance when predicting consequences of changes in prescription.

Clinical and animal studies suggest that peritoneal absorption of fluid and protein from dialysate to peritoneal tissue, and to blood and lymph circulation, occurs concomitantly with opposite flows of fluid and protein, i.e., from blood to dialysate. However, until now a theoretical explanation of this phenomenon has been lacking. A two-phase distributed model is proposed to explain the bidirectional, concomitant transport of fluid, albumin and glucose through the peritoneal transport system (PTS) during peritoneal dialysis. The interstitium of this tissue is described as an expandable two-phase structure with phase F (water-rich, colloid-poor region) and phase C (water-poor, colloid-rich region) with fluid and solute exchange between them. A low fraction of phase F is assumed in the intact tissue, which can be significantly increased under the influence of hydrostatic pressure and tissue hydration. The capillary wall is described using the three-pore model, and the conditions in the peritoneal cavity are assumed commencing 3 min after the infusion of glucose 3.86% dialysis fluid. Computer simulations demonstrate that peritoneal absorption of fluid into the tissue, which occurs via phase F at the rate of 1.8 ml/min, increases substantially the interstitial pressure and tissue hydration in both phases close to the peritoneal cavity, whereas the glucose-induced ultrafiltration from blood occurs via phase C at the rate of 15 ml/min. The proposed model delineating the phenomenon of concomitant bidirectional transport through PTS is based on a two-phase structure of the interstitium and provides results in agreement with clinical and experimental data.

Background 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. Methods 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. Results 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. Conclusions 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.

There are several methods to model the process of water and solute transport during peritoneal dialysis (PD). The characteristics of the phenomena and the purpose of modelling influence the choice of methodology. Among others, the phenomenological models are commonly used in clinical and laboratory research. In peritoneal dialysis, the compartmental approach is widely used (membrane model, three-pore model). These kinds of models are based on phenomenological parameters, sometimes called “lumped parameters”, because one parameter is used to describe the net result of several different processes that occur during dialysis. The main advantage of the compartmental approach is that it decreases substantially the number of parameters that have to be estimated, and therefore its application in clinical research is easier. However, in the compartmental approach, it is usually very difficult to connect the estimated parameters with the physiology and the local anatomy of the involved tissues. Therefore, these models have limited applications in the explanation of the changes that occur in the physiology of the peritoneal transport. For example, the membrane models describe exchange of fluid and solute between peritoneal cavity and plasma through the “peritoneal membrane”. However, this approach does not take into account the anatomy and physiology of the peritoneal transport system and cannot be used for the explanation of the processes that occur in the tissue during the treatment. Basic concepts and previous applications of distributed models are summarized in Section 2. A mathematical formulation of the distributed model for fluid and solute peritoneal transport is also presented in Section 2. The effective parameters, which characterize transport through the peritoneal transport system, PTS (i.e. the fluid and solute exchange between the peritoneal cavity and blood), can be estimated from the local physiological parameters of the distributed models. The comparisons between transport parameters applied in phenomenological description and those derived using a distributed approach, are presented in Sections 3 and 4 for fluid and solute transport, respectively. Typical distributed profiles of tissue hydration and solutes concentration in the tissue are presented in Section 5.

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.

INTRODUCTION Dialysis fluid containing icodextrin is used in patients on peritoneal dialysis (PD) because of its significant ultrafiltration properties. The use of the fluid in treating patients with congestive heart failure resistant to diuretics has also been reported. OBJECTIVES The aim of the study was to evaluate water peritoneal transport during a 16-hour dialysis exchange performed using icodextrin-containing dialysis fluid. PATIENTS AND METHODS Eleven clinically stable patients were enrolled in the study (5 women and 6 men; mean age, 50.4 +/- 18.3 years), treated with PD for 26.9 +/- 22.4 months. Water transperitoneal transport was evaluated using a modified version of Babb-Randerson-Farrell thermodynamic model of membrane transport with human albumin marked with iodine as the marker of intraperitoneal volume. Based on blood and dialysate samples collected during the 16-hour dialysis exchange, the intraperitoneal volume of dialysate and dialysate reverse absorption were calculated. RESULTS There were no clinical complications associated with the use of icodextrin fluid during the study. A significant increase in intraperitoneal volume of dialysate (950 ml on average) compared to the initial value was observed in the whole group at the 16th hour of the exchange. CONCLUSIONS The study demonstrated that dialysis fluid with icodextrin ensured effective ultrafiltration during a 16-hour dialysis exchange. This indicates its potential usefulness in the treatment of patients with severe congestive heart failure with or without coexisting end-stage renal disease.

Based on a distributed model of peritoneal transport, in the present report, a mathematical theory is presented to explain how the osmotic agent in the peritoneal dialysis solution that penetrates tissue induces osmotically driven flux out of the tissue. The relationships between phenomenological transport parameters (hydraulic permeability and reflection coefficient) and the respective specific transport parameters for the tissue and the capillary wall are separately described. Closed formulas for steady-state flux across the peritoneal surface and for hydrostatic pressure at the opposite surface are obtained using an approximate description of the concentration profile of the osmotic agent within the tissue by exponential function. A case of experimental study with mannitol as the osmotic agent in the rat abdominal wall is shown to be well described by our theory and computer simulations and to validate the applied approximations. Furthermore, clinical dialysis with glucose as the osmotic agent is analyzed, and the effective transport rates and parameters are derived from the description of the tissue and capillary wall.

The present article provides a theoretical description of the changes of interstitial hydrostatic pressure, tissue hydration, and protein distribution in the tissue during a peritoneal dwell with isotonic fluid. The mathematical model is based on the concept of uniformly distributed capillary and lymphatic systems within a deformable, porous tissue. Protein transport was analyzed for diffusive and convective transport of serum albumin (SA) and radiolabeled albumin (RISA; added to dialysis fluid) using Darcy's law for fluid flux through the tissue and the two-pore theory for water and protein flow across blood capillary walls. Numerical results showed a local increase of interstitial hydrostatic pressure and tissue hydration over physiologic level in the tissue layer close to the peritoneal surface. The water inflow to the tissue displaced interstitial SA into the deeper tissue layers and yielded RISA accumulation in the tissue at a concentration locally higher than that in the dialysis fluid. The description of water flow agreed with clinical data, but yielded a higher-than-expected hydrostatic pressure in the deep tissue layers. The steady-state rates of fluid and RISA absorption from the peritoneal cavity, but not of SA clearance, agreed with the clinical data.

We investigated a distributed model for the transport of fluid and glucose that allows for the description of hydrostatic pressure, interstitial fluid void volume, and glucose profiles in the tissue. Computer simulations for conditions mimicking the initial minutes of a peritoneal dialysis dwell with 3.86% glucose demonstrated that the rate of fluid flow to the peritoneal cavity was sensitive mostly to the reflection coefficient for glucose in the capillary wall, sigmaCG, whereas the hydrostatic pressure in deep tissue layers was sensitive to the reflection coefficient for glucose in the interstitium, sigmaTG. For hydrostatic pressure in the peritoneal cavity equal to 12 mmHg, sigmaCG = 0.5, sigmaTG = 0.005, and other parameters taken from published physiologic data, the rate of ultrafiltration was about 9 mL/min. Glucose concentration and hydrostatic pressure in the tissue increased in a layer less than 2 mm from the peritoneal cavity; deeper layers were close to their equilibrium values. If a high-value osmotic coefficient for the capillary wall is assumed, the proposed model describes hydrostatic pressure and glucose profiles that agree with available data.

A mathematical model of water flow between dialysis fluid in the peritoneal cavity and blood through the capillary wall and homogeneous interstitium driven by high hydrostatic and osmotic pressure of dialysis fluid is formulated. The model is based on nonlinear equations of reaction-diffusion-convection type. Numerical simulations provide the distribution profiles for hydrostatic pressure, glucose concentration, and water flux in the tissue for different times from the infusion of dialysis fluid into the peritoneal cavity for different transport parameters that represent clinical treatments of peritoneal dialysis.

The evaluation of free water transport is a tool for assessment of aquaporin function in peritoneal dialysis patients. Sodium dip and the estimation of sieving coefficient for sodium may be used for the quantification of free water fraction in the ultrafiltration flow from blood to the peritoneal cavity. The results of clinical studies show that this fraction is about 0.4, and decreases with peritoneal dwell time. The fraction also varies in different peritoneal equilibration test groups, being the lowest in high transporters.

The process of water reabsorption from the peritoneal cavity into the surrounding tissue substantially decreases the net ultrafiltration in patients on peritoneal dialysis. The goal of this study was to propose a mathematical model based on data from clinical studies and animal experiments to describe the changes in absorption rate, interstitial hydrostatic pressure, and tissue hydration caused by increased intraperitoneal pressure after the initiation of peritoneal dialysis. The model describes water transport through a deformable, porous tissue after infusion of isotonic solution into the peritoneal cavity. Blood capillary and lymphatic vessels are assumed to be uniformly distributed within the tissue. Starling's law is applied for a description of fluid transport through the capillary wall, and the transport within the interstitium is modeled by Darcy's law. Transport parameters such as interstitial fluid volume ratio, tissue hydraulic conductance, and lymphatic absorption in the tissue are dependent on local interstitial pressure. Numerical simulations show the strong dependence of fluid absorption and tissue hydration on the values of intraperitoneal pressure. Our results predict that in the steady state only ∼20–40% of the fluid that flows into the tissue from the peritoneal cavity is absorbed by the lymphatics situated in the tissue, whereas the larger (60–80%) part of the fluid is absorbed by the blood capillaries.

To investigate how water flow and interstitial pressure change in tissue during a peritoneal dwell with isotonic fluid, we developed a mathematical model of water transport in the tissue. Transport through muscle alone (M) and through muscle with intact skin (MS) were considered for the rat abdominal wall, using various parameters for muscle and skin. Based on the concept of distributed capillary and lymphatic systems, two main transport barriers were taken into account. capillary membrane and interstitium. We calculated the tissue hydrostatic pressure profiles and compared them with experimental data. The theoretic steady-state pressure distribution for model M is in good agreement with the experimental data. In model MS, the theoretic distribution diverges from the data in the subcutaneous layer. The transient times for fluid flow in the tissue for both model simulations are rather long (40 minutes in model M and 95 minutes in model MS) and depend on intraperitoneal pressure. The fraction of fluid absorbed from the tissue by the lymphatics increases with time from 10% to 97% of fluid flow from the peritoneal cavity.