ISPD

Ultrafiltration Management in Peritoneal Dialysis
Peritoneal Dialysis International, Vol. 20, Suppl. 4
Printed in Canada. All rights reserved.

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Copyright © 2000 International Society for Peritoneal Dialysis

Pathophysiology of Peritoneal Membrane Failure

Raymond T. Krediet,¹ Bengt Lindholm,² and Bengt Rippe³

Division of Nephrology,¹ Department of Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Clinical Science,² Karolinska

Institute, Division of Baxter Novum, Huddinge University Hospital, Huddinge;

Department of Nephrology,³ University Hospital of Lund, Lund, Sweden

Various mathematical models have been used for the assessment of the peritoneum as a dialysis membrane, for example, membrane models and distributed models. These have been discussed by Lysaght and Farrel (1) and by Waniewski (2). The present review is based on the three-pore model (3_5). The peritoneal membrane, as used for peritoneal dialysis (PD), can be divided into three parts for the purpose of simplicity. These are the mesothelium, the interstitial tissue, and the microvessels present in the interstitial tissue. It is unlikely that the mesothelium is an important barrier to solute transport because no osmotic pressure gradient across it was found during PD in rats (6). The barrier function of interstitial tissue is not very well known. Using in vivo microscopy of the rat mesentery, a size-selective restriction in the transport of macromolecules was detected and has been reported (7). More recent studies comparing the transport properties of liver peritoneum (almost no interstitial tissue) with that of parietal peritoneum were unable to show differences (8,9). The capillary wall is probably the most important structure. Solute transport across it is generally considered to occur through a system of pores (10,11). This process occurs mainly through a large number of small pores (radius 40 _ 50 Å), probably represented by paracellular clefts in the endothelium, together with a very low number of large pores (radius approximately 250 Å), allowing transport of macromolecules from blood to peritoneum. In addition, an abundance of water-conductive "ultrasmall pores" (radius approximately 3 _ 5 Å) in the plasmalemma has been assumed, allowing water transport but rejecting the transfer of solutes (3_5). It has been made plausible that aquaporins, and especially aquaporin_1, are the proteins constituting these transendothelial water channels (12_14). For high glucose concentrations (3.86%/4.25%) in dialysis fluid, the three-pore model predicted approximately one half of transperitoneal ultrafiltration (UF) would occur through aquaporins, with the other half through small pores.

Transport of Urea and Creatinine

Diffusion and convection are involved in solute transport from peritoneal capillaries to dialysate. Diffusion is the most important transport mechanism for low molecular weights solutes. Diffusion through the small pore system occurs bidirectionally, depending on the concentration gradient. The rate of diffusion is determined by the product of the mass transfer area coefficient (MTAC, the maximum theoretical clearance by diffusion at time zero) and the concentration gradient. As the latter decreases during a dwell due to saturation of the dialysate, the diffusion rate of urea and creatinine also decreases during a dwell. In a situation where equilibrium is present between plasma and dialysate concentration, the mass transfer will only be determined by the net water transport between blood and dialysate, that is, the drained dialysate volume. Therefore UF rate also contributes to solute removal. This process of solute transport is called convection or solvent drag. The transport of solutes by convection through transcapillary UF does not occur on an equimolar base: in a situation where no diffusion (transport through the small pores) occurs, the dialysate concentration of a solute transported by crystalloid osmosis is lower than the plasma concentration. It is caused by crystalloid osmosis-induced aquaporin-mediated water transport without the transport of solutes. This hindrance to convective solute transport can be expressed as the sieving coefficient (S) (15_18), which is the ratio between the dialysate concentration of a solute and its plasma concentration when no transport by diffusion occurs. It can range between 0 (the solute is too large for transport by convection) to 1.0 (the membrane offers no hindrance to convection solute transport). The sieving coefficient should not be confused with the reflection coefficient s, which is used as a measure of the effectivity of a solute to create a crystalloid osmotic pressure gradient across a membrane. It can also range between 1.0 (no passage, ideal semipermeable membrane) to 0 (no osmotic effect). For a homoporous membrane S = 1 _ s. The heteroporosity of the peritoneal membrane is the explanation of why the above equation does not apply in PD. Typical values for S of low molecular weight solutes average 0.7 (15_18), but s values of 0.05 or less are normally reported (19_23).

The permeability of the peritoneum to the transport of low molecular weight solutes has traditionally been investigated during 4-hour dwells, such as in the peritoneal equilibration test (PET) (24). Parameters that can be calculated from such a standardized test are the MTAC of a solute, its dialysate-to-plasma (D/P) ratio, and the clearance of that solute. Because transcapillary transport is the major process in PD, and because the peritoneum offers no size-selective restriction barrier to the transport of low molecular weight solutes (25), the MTAC or D/P ratio is determined mainly by the vascular peritoneal surface area. Under basal circumstances only about 25% _ 50% of the peritoneal capillaries are perfused (26,27). This number can be increased by, for example, the administration of nitroprusside (26,28). The importance of this is emphasized by the observation that peritoneal blood volume is a more important determinant of diffusion rate than is peritoneal blood flow (29). For practical reasons, changes in the D/P ratio of a solute or in its MTAC can be considered to represent changes in the vascular peritoneal surface area. These changes can be either functional (more perfused capillaries) or anatomic (more capillaries present).

Based on D/P creatinine, patients have been classified into four transport categories: low, low-average, high-average, and high. However, because peritoneal mass transfer and peritoneal clearance of a small solute during dwells of 4 hours or more are dependent mainly on drained volume, patients with a high D/P ratio of creatinine may in fact have a low mass transfer and clearance of this solute (30). Therefore, the classification into transport categories based on D/P ratios may be confusing. Because the D/P ratio of low molecular weight solutes is dependent mainly on the surface area of the peritoneal membrane (see above), renaming of the four "transport" categories should be considered. They could be named either high, high-average, low-average, and low D/P ratio creatinine or, alternatively, very large, large, medium, and small surface area.

Physiology of Fluid Transport

Fluid transport during PD is determined by hydrostatic and osmotic pressure, and also by lymphatic drainage. Transcapillary UF rate is dependent on the hydraulic permeability of the peritoneum, its effective surface area, and the hydrostatic, colloid osmotic, and crystalloid osmotic pressure gradients. The hydrostatic pressure in the peritoneal capillaries is assumed to be 17 mmHg (31). Intraperitoneal pressure during continuous ambulatory peritoneal dialysis (CAPD) in the supine position averages 8 mmHg (32), but exceeds 20 mmHg while walking (33). It is also dependent on instilled dialysate volume (34). This implies that the hydrostatic pressure gradient is mainly dependent on intraperitoneal pressure. Colloid osmotic pressure in the peritoneal capillaries probably averages 26 mmHg (31). In CAPD patients who have a mean serum albumin concentration of 34 g/L (35), a value of 21 mmHg can be calculated (36). The contribution of dialysate to the colloid osmotic pressure gradient can be neglected because of its low protein content.

The crystalloid osmotic pressure gradient during PD with conventional solutions is determined mainly by glucose. Its effectiveness as an osmotic agent depends on the resistance the membrane exerts to glucose transport. This is expressed as the osmotic reflection coefficient. It can range from 1 (no passage, ideal semipermeable membrane) to 0 (passage not hindered). According to van 't Hoff's law, 1 mOsm/kg H₂O exerts an osmotic pressure of 19.3 mmHg when the reflection coefficient is 1.0. The osmotic pressure created by a low molecular weight solute equals the product of the osmolality gradient and the reflection coefficient of that solute, multiplied by 19.3. A value as low as 0.03 for glucose has been calculated in CAPD patients (22). It is likely that the reflection coefficient of glucose in the small pores will be very low, but will approach 1.0 across the ultrasmall pores. This might explain why glucose is an effective osmotic agent despite its small size. The maximal pressure gradients during the beginning of a dialysis exchange are summarized in Table 1. The concentration gradient of glucose is maximal during the start of a dialysis exchange and decreases during the dwell because glucose is absorbed from the dialysate. This glucose absorption averages 61% of the instilled quantity during a 4-hour dwell (37) and 75% after 6 hours (38). The absolute but not the relative absorption is influenced by the glucose concentration used (39). As a consequence, the transcapillary UF rate has its maximum value at the start of dialysis and decreases during the dwell.

TABLE 1 Pressure Gradients Across the Peritoneal Membrane During Peritoneal Dialysis

	Pressure in peritoneal capillaries	Pressure in dialysate-filled peritoneal cavity	Pressure gradient

Hydrostatic pressure (mmHg)	17	8 Recumbent	9
Colloid osmotic pressure (mmHg)	21	0.1	_21
Osmolality (mOsm/kg H₂O)	305	347 (Glucose 1.36%)
		486 (Glucose 3.86%)
Maximal crystalloid osmotic pressure gradient (mmHg)		Glucose 1.36%	(347_305)×0.03×19.3=24
		Glucose 3.86%	(486_305)×0.03×19.3=105
Net maximal pressure gradient (mmHg)		Glucose 1.36%	12
		Glucose 3.86%	93

The reflection coefficient of low molecular weight solutes is set at 0.03.

Dextrins are glucose polymers that can also be applied as osmotic agent during PD. Icodextrin, a disperse mixture of dextrins with an average molecular weight of 16800 D, is currently used in clinical practice (40). Due to its high molecular weight, icodextrin is likely to induce colloid osmosis (41). This implies that macromolecules are able to induce transcapillary UF even in an isotonic or a hypotonic solution. The process of colloid osmosis is based on the principle that fluid flow across a membrane that is permeable to small solutes occurs in the direction of relative excess of impermeable large solutes, rather than along a concentration gradient. Consequently, dialysis solutions containing macromolecules to remove fluid from the body will induce water transport through the small-pore system. The amount of fluid transported through the ultrasmall water channels is negligible because the resistance in the aquaporins is much higher than in the small pores due to the difference between the two in radius. Water channels require very high osmotic pressure gradients. This is explaned in a mathematical way in Appendix A. It can be calculated from the osmolality gradients given in Table 1 that the crystalloid osmotic pressure gradient across the water channels is (347 _ 305) × 19.3 = 811 mmHg for a 1.36%/1.5% glucose solution, and (486 _ 305) × 19.3 = 3493 mmHg for a 3.86%/4.25% glucose solution. The pressure gradients across the peritoneal membrane that can be expected using a monodispersed 7.5% icodextrin-based dialysis solution are shown in Table 2. It follows from this Table that the maximum pressure gradient across the peritoneal membrane is 42 mmHg, which is higher than the 12 mmHg exerted by 1.36%/1.5% glucose, but markedly lower than the 93 mmHg exerted by 3.86%/4.25% glucose. However, because of its lower absorption, the gradient will remain present for a much longer time. Commercially available icodextrin solutions are not monodispersed, but polydispersed (42). The colloid osmotic pressure gradient for a number average MW of 6200D is also shown in Table 2.

The maximal transcapillary UF values during the first few minutes of an exchange have been reported to average 2.7 mL/min (43) and 4.3 mL/min (4) for dialysate containing 70 mmol/L (1.36%/1.5%) glucose. For 200 mmol/L glucose (3.86%/4.25%), these values average 15 mL/min (25,38,44,45). Mean values for transcapillary UF during 4-hour dwells average 1.0 _ 1.2 mL/min for 1.36%/1.5% glucose (25,37,43), and 3.4 mL/min for 3.86%/4.25% glucose (25). The transcapillary UF rate for 7.5% icodextrin is more or less constant during a 4-hour dwell and averages 1.4 _ 2.3 mL/min (36,46). Knowledge of pressure gradients and maximum transcapillary UF rates makes it possible to calculate the peritoneal UF coefficient (PUFC), which is the product of the peritoneal surface area and its hydraulic permeability (L_pS). This is further explained in Appendix A.

The lymphatic absorption rate from the peritoneal cavity can be measured either as the disappearance rate of intraperitoneally (IP) administered macromolecules (47_49), or as its appearance rate in the circulation (50,51). For the latter, the use of a radioactive-labeled marker, such as iodinated albumin, is required. The disappearance rate overestimates direct absorption into the lymphatics because the tracer is also transported across the mesothelial layer to peritoneal interstitial tissue (52). The appearance rate underestimates lymphatic uptake because only 40% _ 50% of the total albumin mass is intravascular (53). The plasma appearance rate shows remarkably little variability (51) and is not influenced by an increased intraperitoneal pressure (54). In contrast, the disappearance rate increases, the greater the instilled dialysate volume (55) and the higher the intraperitoneal pressure (32,54). An effect of position on disappearance rate can be neglected because it is only marginal (56). Interventions aimed at reducing the lymphatic absorption rate, such as with IP phosphatidylcholine (57,58) or with IP hyaluronan (51), especially affect disappearance rate.

TABLE 2 Pressure Gradients Across the Peritoneal Membrane During Peritoneal Dialysis Using 7.5% Icodextrin

	Pressure in peritoneal capillaries	Pressure in dialysate-filled peritoneal cavity	Pressure gradient

Hydrostatic pressure (mmHg)	17	8 Recumbent	9
Colloid osmotic pressure (mmHg)	21	M: (75×0.767×19.3)/16.8=66	45
		P: (75×0.21×19.3)/6.2=49	28
Osmolality (mOsm/kg H₂O)	305	285
Maximal crystalloid osmotic pressure gradient (mmHg)			(285_305)×0.03×19.3=_12
Net maximal pressure gradient (mmHg)			42 (M)
			25 (P)

It is assumed that the molecular weight (MW) of icodextrin is 16800 and the reflection coefficient is 0.767 (M = monodispersed). For a polydispersed solution (P), the number average MW is set at 6200, and the reflection coefficient at 0.21. The reflection coefficient of low MW solutes is set at 0.03.

When radiolabeled albumin is used as a tracer, both disappearance rate and appearance rate can be measured simultaneously. The difference between the two has been assumed to represent transmesothelial clearance (51). Whatever the mechanism, convective transport of solutes out of the peritoneal cavity is different from that into it, as sieving does not occur because solutes are either transported transmesothelially or taken up directly into the lymphatic system. The contribution of convection to diffusive transport from the peritoneal cavity is relatively small for low molecular weight solutes, but becomes increasingly more important the higher the molecular weight of a solute. The convection/diffusion ratio is about 0.1 for glucose, 1.0 for inulin (59), but 10 for IP administered autologous hemoglobin (60), making the disappearance rate of IP administered macromolecules relatively independent of molecular size (61).

Glucose and Sodium Transport

Diffusion is the dominant transport process for glucose, especially when a hypertonic solution is used. However, the process of glucose transport from dialysate to blood is not very well understood. Recent studies suggested that facilitated glucose transport mediated by glucose transporters might also be involved in this process, although it is not clear to what extent these mesothelial glucose transporters contribute to its transport (62,63). Convection by UF significantly decreases the dialysate glucose concentration by dilution (64). Also, the contribution of peritoneal fluid absorption in the removal of glucose is not negligible because of the very high dialysate glucose concentrations, although its relative contribution is less than that of diffusion.

The dialysate concentration of sodium decreases during the initial phase of a dialysis dwell using hypertonic solutions, followed by a gradual rise (18,38,45,47,65,66). The minimum value is usually reached after 1 _ 2 hours. It is likely that this so-called sieving of Na⁺ is caused by transcellular water transport through ultrasmall pores. However, other mechanisms such as temporal binding of Na⁺ in the interstitial tissue cannot be excluded with certainty. Water transport rates are high during the initial phase of a hypertonic exchange. Therefore the decrease in dialysate Na⁺ is a dilutional phenomenon (67). This implies that, during short dwells using hypertonic dialysate, much more water than Na⁺ is removed from the extracellular volume. This can lead to hypernatremia (16). The gradual rise during the subsequent hours is probably caused by diffusion of Na⁺ from the circulation.

The MTAC of Na⁺ is difficult to calculate due to the small differences in dialysate and plasma concentrations. Using 3.86% glucose dialysate, an average value of 4 mL/min has been reported during a period of isovolemia (38,64). This may be an underestimation, due to the small diffusion gradient, because average values of 7 _ 8 mL/min have been found using dialysate with a Na⁺ concentration of 102 _ 105 mmol/L (22,68). All these values are markedly lower than those reported for uncharged low molecular weight solutes, such as urea and creatinine. The Na⁺ concentration in most currently used dialysis fluids is close to or slightly lower than the plasma Na⁺ concentration, that is, Na⁺ transport is accomplished almost in the so-called isocratic condition. Therefore, the diffusive transport component plays a minor role in peritoneal Na⁺ transport, except in patients where a high peritoneal Na⁺ gradient is present and that have a large vascular surface area. In general however, convection, including UF-induced Na⁺ transport and transport by peritoneal absorption, dominates Na⁺ transport (66). Similar mechanisms apply for the transport of calcium (69,70).

Glucose and Na⁺ Transport in Relation to Peritoneal Permeability Characteristics

Recently, several reports have indicated that the CAPD patient's peritoneal permeability characteristics have a significant impact on clinical outcome, including patient and technique survival (30,71_75). High D/P ratios of low molecular weight solutes were associated with a lower patient survival (30,75). With a detailed evaluation of the peritoneal transport characteristics among the different patient groups, it appeared that high D/P ratios were associated with higher glucose absorption (increased diffusive transport and increased convective transport associated with fluid absorption) and therefore lower fluid and Na⁺ removal (30).

The Na⁺ transport pattern differed significantly among different D/P creatinine groups. Patients with high D/P ratios had significantly lower convective Na⁺ mass transport associated with UF, and significantly higher convective Na⁺ mass transport associated with fluid absorption, when compared to patients with low D/P ratios (66). Additionally, patients with high D/P ratios had a high sieving coefficient for Na⁺ and a high D/P Na⁺ value, suggesting that reduced UF may also be related to a lower number of, or impaired function of water pores in these patients (66). It also appeared that D/P Na⁺ values, especially during the later part of the dwell (4 _ 6 hours) (66), or even a dialysate Na⁺ concentration at 240 minutes (76) of the dwell using 3.86%/4.25% glucose dialysis solution, could be used to classify patients' peritoneal permeability characteristics. Further studies are needed to evaluate clinical application.

Pathophysiological Mechanisms of Peritoneal Membrane Alterations Leading to UfF in Long-Term PD

Peritonitis causes a reversible loss of UF due to rapid dissipation of the osmotic gradient across the membrane, as discussed in the section on peritoneal transport during peritonitis. The question to what extent peritoneal inflammation is involved in the pathogenesis of established UFF and peritoneal sclerosis is much more difficult to answer. Acute peritonitis causes mesothelial cell damage (123). However, dialysate concentrations of the mesothelial cell mass marker CA125 were not lower than expected after recovery from infection (124,125). Also, no relationship between individual trends in transport and peritonitis incidence was found in a prospective study during a 2-year follow-up (126). This is in accordance with findings in children, where no significant difference in peritonitis incidence was found between those with and those without membrane failure (127). Peritonitis incidence was also not a significant risk factor for the development of peritoneal sclerosis (128,129).

These negative findings do not exclude a contribution of peritonitis to the pathogenesis of membrane failure. The development of UFF associated with high D/P ratios was especially marked in patients with multiple infection episodes in two prospective studies (130,131). This was related to either the severity of the inflammatory reaction (131), the accumulated days of peritoneal inflammation (130), or the micro-organism (127). Episodes caused by Pseudomonas and Staphylococcus aureus have been especially implicated (127,131). The majority of patients with peritoneal sclerosis had persistent or relapsing peritonitis in the last few months of PD treatment (129). Candida, Pseudomonas, and S. aureus were cultured most often in these episodes. This supports the hypothesis that these micro-organisms in particular can cause severe peritonitis when an already damaged peritoneum is present, thereby enhancing the progression to overt peritoneal sclerosis.

It emerges from the above data that severe and multiple peritonitis episodes may contribute to the development of membrane failure. However, it is unlikely to be the only or even the most important cause. This is illustrated by the development of membrane failure in long-term patients with no or very few episodes of peritonitis [Ref. (132) and B. Faller, personal communication]. The relationship between the duration of PD and the occurrence of membrane failure suggests that continuous exposure to nonphysiologic dialysis fluids is an important factor. During the past few years an increasing amount of circumstantial evidence has come out of studies in animals and patients, that especially glucose is involved in the development of various alterations in the peritoneal membrane. Glucose was more toxic to mesothelial cells in a chronic animal model than were low pH, lactate, and hyperosmolality (133). In addition, glucose passes the mesothelium easily, exposing all peritoneal tissues to extremely high glucose concentrations. These concentrations are much higher than those normally found in the plasma of patients with diabetes mellitus. This may explain the diabetiform alterations in the peritoneal microvasculature, such as reduplications of the capillary basement membrane (134) and the marked increase in the number of microvessels (135) with deposition of collagen IV (135,136). In a recent study, fibrotic and vascular alterations could be induced in a chronic rat model with daily infusion of 3.86%/4.25% glucose during 20 weeks (137). Infusion of a Ringer's lactate solution caused no peritoneal abnormalities.

Accumulation of advanced glycosylation end-products (AGE) has also been described (138), especially in the vascular walls (139).

The combination of neoangiogenesis with the deposition of extracellular matrix resembles the abnormalities found in diabetic microangiopathy. Vascular endothelial growth factor (VEGF) is the most important growth factor involved in the neoangiogenesis of diabetic retinopathy (140). Similarly, transforming growth factor b (TGFb) is a key mediator in the extracellular matrix expansion present in diabetic nephropathy (141). It was recently found that dialysate levels of VEGF and TGFb in CAPD patients exceeded expected concentrations when only transport from the circulation would have occurred (142). Interestingly, VEGF levels were correlated with MTAC creatinine and inversely correlated with the transcapillary UF rate. High dialysate VEGF concentrations resemble the situation in diabetic retinopathy where VEGF in ocular fluid was increased in patients with proliferative diabetic retinopathy (143,144).

Patients with peritoneal sclerosis had a greater cumulative glucose exposure, in a retrospective analysis, than their controls matched for the duration of CAPD (129). All this evidence suggesting an important pathogenetic role for glucose, does not exclude an additive contribution of acidity or of glucose degradation products formed during heat sterilization of dialysis fluids.

In this paper on pathophysiology of peritoneal membrane failure, the peritoneal transport mechanisms of solute and fluid transport have been discussed, followed by the pathophysiological mechanisms and causes of impaired ultrafiltration. Evidence has been presented pointing to diabetiform peritoneal neoangiogenesis as the main, but not the only cause of UFF.

Appendix A

The peritoneal ultrafiltration (UF) coefficient (PUFC) is the product of the hydraulic permeability of the peritoneum (L_p) and the surface area (S). It can be calculated from the maximal transcapillary UF rate (TCUFR_max), as present during the first minute of a dwell, and the overall peritoneal pressure gradient according to the Starling equation

TCUFR_max = L_pS(DP _ sDP + sDO) (A1)

in which DP is the hydrostatic pressure gradient, DP the colloid osmotic pressure gradient, DO is the crystalloid osmotic pressure gradient, and s is the reflection coefficient. For DP, a s value of 1.0 is usually assumed. For glucose, a reflection coefficient of 0.03 has been calculated in CAPD patients, based on the three-pore model (22). Another, simpler approach to estimate s of the overall crystalloid osmotic pressure gradient is a comparison between 1.36%/1.5% glucose and 3.86%/4.25% glucose dialysate. For 1.36%/1.5% glucose dialysate, the following substitution can be made based on the values presented in Table 1 and in the section on physiology of fluid transport:

2.7(mL/min) =L_pS[9_21+s(42×19.3) mmHg]. (A2)

For 3.86%/4.25% glucose the following values apply:

15 (mL/min) = L_pS[9 _ 21 + s(181×19.3) mmHg]. (A3)

Because L_pS is the same in Eqs (A2) and (A3), a value of 0.05 can be calculated for s of the crystalloids that exert the crystalloid osmotic pressure gradient. In the three-pore model (Appendix C), a value of 0.05 is assumed.

Substituting s = 0.03 in Eq (A1) yields for 3.86%/4.25% glucose

15 (mL/min) = L_pS(9 _ 21 + 105 mmHg),

L_pS = 0.16 mL/min/mmHg.

The osmotic conductance (L_pS × s) is

0.16 × 0.03 = 4.8 mL/min/mmHg.

When s = 0.05 is substituted in Eq (A1) the following is obtained with 3.86%/4.25% glucose:

15 (mL/min) = L_pS(9 _ 21 + 175 mmHg),

L_pS = 0.09 mL/min/mmHg.

The osmotic conductance (L_pS × s) is

0.09 × 0.05 = 4.5 mL/min/mmHg.

These examples show very clearly that small differences in s lead to markedly different values for L_pS, but that their effect on the osmotic conductance of the peritoneum is limited. It should be appreciated that the L_pS determined with 3.86%/4.25% glucose dialysate is based on fluid transport through the paracellular pore system and through aquaporins.

The PUFC through the paracellular pore system can be calculated in a similar way using data obtained with 7.5% icodextrin. This is done using the pressures and assumptions for s given in Table 2:

monodispersed:

2 mL/min = L_pS(9 + 45 _ 12 mmHg),

L_pS = 0.05 mL/min/mmHg;

polydispersed:

2 mL/min = L_pS(9 + 28 _ 12 mmHg),

L_pS = 0.08 mL/min/mmHg.

When the negative crystalloid osmotic pressure gradient is omitted, because this equilibrates rapidly, L_pS will be 0.04 mL/min/mmHg. It should be appreciated that calculation of the osmotic conductance to icodextrin will result in values that are about 10 times higher than those found for glucose-based solutions.

Using L_pS through the small pores obtained with icodextrin, the back-filtration rate of dialysis fluid into the capillaries by the colloid osmotic pressure gradient can be estimated:

back-filtration rate monodispersed:

0.05(9 _ 21) = 0.6 mL/min;

polydispersed:

0.08(9 _ 21) = 0.96 mL/min.

In a previous study using a dialysis solution without an osmotic agent, the overall osmotic back-filtration rate was 0.9 mL/min during a 4-hour dwell (145). It was highest during the start of the dwell (2.6 mL/min) because the solution was hypotonic to uremic plasma, and averaged 0.4 mL/min during the last 2 hours. A value of about 1 mL/min can be calculated on data from a study using IP 0.9 NaCl (146).

The most probable explanation for the apparent differences for L_pS values calculated above using either glucose or icodextrin, while L_pS is a membrane property that is constant by definition, is the heteroporosity of the peritoneum. The presence of water channels is especially important in this respect because they represent only a small proportion of the surface area, but contribute largely to water flow induced by crystalloid osmosis. This is illustrated by the following examples that are based on a contribution of the aquaporin pathway to total L_pS of 2%. This figure has been used in computer simulations based on the three-pore model. Despite the small contribution by aquaporins to total peritoneal L_pS, a very large proportion of the osmotic force is exerted across this pathway. This is because the osmotic force is composed of the fractional L_pS values (across paracellular pores and aquaporins), each multiplied by the solute reflection coefficient across each pore system.

For glucose the following calculation can be made, assuming a reflection coefficient of 1.0 across aquaporins and 0.03 across the paracellular pores. The partial osmotic forces are as follows:

aquaporins: 0.02 × LpS × 1.0

paracellular pores: 0.98 × LpS × 0.03 = 0.0294 × LpS.

The fractional osmotic force across aquaporins now becomes:

0.02 LpS/(0.02 + 0.0294)LpS = 0.40.

Thus 40% of the water flow will initially occur through aquaporins.

aquaporins: 0.02 × LpS × 1.0

paracellular pores: 0.28 × LpS × 0.767 = 0.7517 × LpS.

The fractional osmotic force across aquaporins now becomes

0.02LpS/(0.02 + 0.7517)LpS = 0.03.

Consequently only 3% of the water flow induced by icodextrin will occur through aquaporins.

Well-functioning aquaporins are assumed in the above calculations. However, malfunction of these water channels may contribute to UFF in long-term PD patients. The contribution of aquaporin-mediated water transport to total transcapillary UF can be estimated in individual patients by comparing their initial UF rates during a study with 3.86%/4.25% glucose and one during 7.5% icodextrin. From these values and the transperitoneal pressure gradient, PUFC can be calculated for glucose and for icodextrin. PUFC_glucose is determined by water transport through the paracellular and the transcellular pores, while PUFC_ico represents mainly paracellular water transport. Subtraction of PUFC_ico from PUFC_glucose therefore gives the PUFC through the water channels. Using this approach in stable CAPD patients it appeared that aquaporin-mediated water transport contributed to over-all water transport by 50%, on the average (36). This value is similar to that obtained using computer simulations of the three-pore model, but the range among individual patients appeared very wide. The lowest values for transcellular water transport were found in long-term CAPD patients (36).

Appendix B

The MTAC of a solute is the maximum theoretical clearance by diffusion at time zero of a dwell, that is, before any transport of that solute has occurred. In clinical practice, the MTAC can be calculated easily when either the Henderson and Nolph equation (147) or the simplified Garred equation (148) is used. The Henderson and Nolph equation can be written as:

MTAC =	V_D	ln	(P \| D₀)	.	(A4)

	t		(P \| D_t)

The simplified Garred equation also includes volume changes to some extent:

MTAC =	V_D	ln	V₀ (P \| D₀)	.	(A5)

	t		V_D(P \| D_t)

In these equations V_D is the drained volume, t is the dwell time (240 minutes), V₀ is the instilled dialysate volume, P is the plasma concentration, D₀ is the dialysate concentration before inflow (important for creatinine because of glucose interference), and D_t is the dialysate concentration at the end of the dwell, normally determined in the dialysate after drainage. The plasma concentrations of urea and creatinine should be expressed per plasma water (64), using a correction factor of 1.05 for example. Several more complicated equations can be applied, but these require the use of an IP administered macromolecular tracer. In the Waniewski formula a factor F is used to correct for convective transport (149,150); it can range from 0.5 to 0.33, the latter being especially justified for situations with high transcapillary UF rates:

MTAC =	V_M	ln	V^{1 \| F} (P \| D₀)	,	(A6)

	t		V^{1 \| F}(P \| D_t)

in which V_m is the mean intraperitoneal volume. A further refinement can be obtained using (151)

MT = MTAC(P _ D) + S(TCUFR)P _ LAR × D, (A7)

in which MT is the total mass transfer, S is the sieving coefficient, TCUFR is the transcapillary UF rate, and LAR is the lymphatic absorption rate.

Equation (A4) is especially appropriate during a period of relative isovolemia (152), such as when 1.36%/1.5% glucose dialysate is used. Equation (A5) is preferably used when 3.86%/4.25% glucose is employed. The differences between Eqs (A5) and (A6) are not clinically important for the calculation of MTAC (25,149,150).

Appendix C

In this Appendix, computer simulations of intraperitoneal volume and dialysate Na⁺ concentration will be presented for the different causes of UFF. These simulations are based on the three-pore model. In this model, an abundance of aquaporins (12_14), water-conductive "ultrasmall" pores (radius approximately 3 _ 5 Å) in the plasmalemma, rejecting solute transport, play an important role in peritoneal osmotic water transport and solute sieving. For high glucose concentrations in the dialysis fluid, the three-pore model predicts approximately one half of transperitoneal UF will occur through aquaporins, whereas the other half is modeled to occur through small pores (3). The membrane factors that determine UFF in CAPD patients are the permeability surface area product (PS or MTAC) of the osmotic agent, the membrane UF coefficient (L_pS), and the reflection coefficient (s) of the osmotic agent in the membrane (105). For a small solute, the latter is critically dependent on the fraction (a) of the hydraulic conductance accounted for by the aquaporins, here denoted a_c. Actually, in the absence of aquaporins, the reflection coefficient to glucose (s_g) would be 0.03 instead of 0.05, which is the value predicted for the three-pore membrane (a_c = 0.02). The initial rate of UF occurring during a single dwell is highly dependent on the product of the L_pS and s_g, and also on the transperitoneal glucose concentration gradient; while PS for glucose, which determines the rate of glucose removal from the peritoneal cavity, influences the cumulative amount of UF volume obtained during the first few hours of a dwell. A high PS (MTAC) for glucose, or a low mass of intraperitoneal glucose (due to, e.g., a low intraperitoneal volume) will thus reduce the UF volume as well as the time to the peak of the UF curve (t_peak) (5).

According to pore theory, four major causes of UFF can be distinguished based on their etiologies: (1) UFF due to an enlarged "effective" vascular surface area, (2) UFF due to a reduced osmotic conductance to glucose (L_pS s_g), (3) UFF due to increases in fluid (and macromolecule) absorption from the peritoneal cavity, and (4) UFF due to an extremely small vascular surface area due to multiple adhesions.

In the following section, computer modeling outputs will be presented consistent with these different kinds of UFF based on the three-pore model. The technique for this computer simulation has been presented earlier (3_5,42). The specific parameters used to simulate control conditions for 3.86%/4.25% glucose are shown in Table 3. Note that the parameters used in this table are not always identical to those described in Appendix A.

TABLE 3 Parameters Used for Computer Simulations of Intraperitoneal Volume V(t)-Versus-Time Curves According to a Three-Pore Model of Membrane Selectivity

Small pore radius (r_S)	43 Å
Large pore radius (r_L)	250 Å
Fractional small pore ultrafiltration coefficient (a_S)	0.900
Fractional transcellular ultrafiltration coefficient (a_c)	0.020
Fractional large pore ultrafiltration coefficient (a_L)	0.080
Fractional large pore surface area	0.002
Molecular radius of sodium (and chloride)	2.3 Å
Molecular radius of urea	2.6 Å
Molecular radius of glucose	3.7 Å
Molecular radius of albumin ("total protein")	36 Å
Ultrafiltration coefficient (L_pS)	0.076 mL/min/mmHg
Osmotic conductance to glucose (L_pSs_g)	3.5 mL/min/mmHg
"Unrestricted" pore area over unit diffusion distance (A₀/DX)	25000 cm
PS ("MTAC") for glucose	15.5 mL/min
PS ("MTAC") for sodium	6 mL/min
Peritoneal lymph flow (L)	0.3 mL/min
Transperitoneal hydrostatic pressure gradient (DP)	9 mmHg
Transperitoneal colloid osmotic pressure gradient (DP_prot)	22 mmHg
Dialysis fluid volume instilled	2050 mL
Peritoneal residual volume	300 mL
Plasma urea concentration	20 mmol/L
Plasma sodium (and sodium associated "anion") concentration	140 mmol/L
Dialysis fluid sodium concentration	132 mmol/L
Plasma glucose concentration	6 mmol/L

PS ("MTAC") = permeability surface area product or mass transfer area coefficient.
Reflection coefficients for all solutes in the transcellular pathway were set to 1. A majority of simulations were performed for 3.86%/4.25% glucose in the dialysis fluid infused.

Low UF Caused by a Large Vascular Surface Area

Figure 1(a) — Simulated drained volume-versus-time curves as a function of surface area (S), which is varied from 0.1 to 3.0 of control. This implies that both peritoneal surface area (PS) for glucose and its hydraulic permeability (L_pS) are varied from 0.1 times control (denoted "0.1") to 3 times control (denoted "3.0"). Note that when S is reduced to one half or doubled, the reduction in drained volume after 250 minutes is rather small. Simulations are done for 3.86%/4.25% glucose in the dialysis fluid.

Figure 1(b) — Effects of varying PS for glucose from 0.5 times control to 3 times control, concomitantly varying L_pS to a lesser degree. For every step change in PS for glucose, L_pS is altered 33%. A doubling in PS for glucose thus implies a 33% increment in L_pS. All curves are simulated for 3.86%/4.25% glucose in the dialysis fluid.

Figure 1(c) — Dialysate sodium as a function of time ("sodium sieving curves") corresponding to the ultrafiltration curves in Figure 1(b). When PS for glucose is increased, sodium sieving is decreased and the time to maximum dip in dialysate sodium is reduced.

Theoretically, increases in capillary surface area (S) would most likely cause increases in both PS for small solutes and PUFC (L_pS). However, the reductions in UF volume at 240 _ 300 minutes obtained when both these parameters are perturbed to the same extent are rather minor. This is illustrated in Figure 1(a) where UF profiles for 3.86%/4.25% glucose are shown for a variety of perturbations in S (surface area). Due to the rather unchanging UF profiles occurring for moderate variations in S, it is hypothesized that the UFF occurring as a consequence of long-term CAPD may be due to mainly an increase in small solute PS combined with a lesser increase in the peritoneal L_pS, or peritoneal osmotic conductance (L_pSs). Such a scenario is depicted in Figure 1(b). Here, for every step change in PS, the corresponding change in L_pS occurs by 33%. Thus a doubling of PS is associated with a 33% increment in L_pS. Note that in this case, unlike in case 1(a), there is a marked reduction in the UF volume at 240 _ 300 minutes for 3.86%/4.25% glucose. In Figure 1(c) the Na⁺ sieving curves corresponding to the UF profiles shown in Figure 1(b) are presented. When vascular surface area is increased (i.e., when PS for glucose is increased), Na⁺ sieving is reduced. Note also that for increasing PS values, the time to the maximum dip in Na⁺ concentration will decrease.

Low UF Caused by a Reduced Osmotic Conductance to Glucose

A Decreased UF Coefficient (L_pS): Since the rate of UF is highly dependent of the product of L_pS and s_g, changes in either L_pS or s_g (the latter dependent on the near 50% contribution from the aquaporins) will yield approximately similar results. Note, however, how small changes in L_pS alone will markedly affect the "height" of UF curves (but not the time to curve maximum, t_peak). Note also (PS for small solutes kept unchanged) that changes in L_pS imply increases in both the initial UF rate and in the peritoneal-to-blood absorption rate ensuing upon the curve peak [Figure 2(a)]. When L_pS is reduced, Na⁺ sieving is also reduced, although there are no selective changes in aquaporin-mediated water flow [Figure 2(b)].

A Decreased Glucose Reflection Coefficient (s_g): Some patients with marked UFF in the absence of increases in small solute transport (case 1) or lymph flow (case 3, see below) also show markedly impaired, or nearly absent, Na⁺ sieving for 3.86%/4.25% glucose (104,110). This has been suggested to indicate that a reduced aquaporin-mediated osmotic water flow may have been responsible for the UFF (104,110). It should, however, be noted that patients with the most significant depression of UF, regardless of cause, should also theoretically show the largest reduction in Na⁺ sieving. A low rate of UF thus automatically yields a low degree of Na⁺ sieving! Figure 3(a), taken from a previous publication (105), actually shows some of the theoretical cases of UFF discussed above for 3.86%/4.25% glucose. Curve A shows the situation for normal conditions, curve B represents a case where PS for glucose has been increased 70% while L_pS is kept constant, and curve C represents a case where L_pS has been reduced by 50% (keeping PS constant). Curve D refers to a situation where the fraction of L_pS accounted for by aquaporins (a_c) has been reduced from 0.02 to 0.002. Note that curves C and D are almost identical, implying that changes in either s (or actually a_c, which is a main determinant of s_g) or L_pS can induce similar changes in the UF profile, whereas curve B has an earlier peak than the other two curves. The situation illustrated by curve B is easily revealed by the increased D/P for creatinine or urea, or the reductions in D/D₀ for glucose, that will be obtained in an ordinary PET. Curves C and D are, however, almost identical. The difference between case C and case D can be revealed only by assessing Na⁺ concentration as a function of dwell time for hypertonic glucose, as shown in Figure 3(b). In case D (no aquaporin-mediated water flow), there is no Na⁺ sieving at all, whereas in both case B and case C this Na⁺ sieving is markedly attenuated.

Figure 2(a) — Effects of varying L_pS (the ultrafiltration coefficient) from 0.5 times control (denoted "0.5") to 3 times control (denoted "3.0") for 3.86%/4.25% glucose in the dialysis fluid. A markedly reduced L_pS will cause a flattened ultrafiltration profile.

Figure 3(a) — Computer simulated drained volume-versus-time curves for control conditions (A), a situation when PS for glucose is increased by 70% (B), when L_pS is reduced to 50% of control value (C), and when the fractional L_pS through aquaporins is reduced from 0.02 to 0.002 (D). Simulations are done for 3.86%/4.25% glucose in the dialysis fluid. (From Rippe B. Perit Dial Int 1997; 17:125_8.)

Figure 2(b) — Sodium profiles (mmol/L) corresponding to the curves in Figure 2(a). When ultrafiltration profiles are flattened, sodium sieving is also reduced, although aquaporin-mediated water flow is not selectively affected.

Figure 3(b) — Computer simulated dialysate sodium (mmol/L) versus time for the scenarios depicted in Figure 4(a) (3.86%/4.25% glucose). (From Rippe B. Perit Dial Int 1997; 17:125_8.)

One should, however, bear in mind that it may be difficult in the clinical situation to distinguish between patients with markedly reduced UF coefficient (showing an even more attenuated Na⁺ sieving than in case C) and patients with an assumed selective reduction in aquaporin-mediated water flow. To really prove the occurrence of a reduced aquaporin-mediated UF capacity in these patients, the degree of Na⁺ sieving should be tested for a still more hypertonic solution than for 3.86%/4.25% glucose (e.g., for 6.0% glucose). In a patient with a reduced peritoneal L_pS, Na⁺ sieving will then improve to again approach that occurring in normal patients for 3.86%/4.25% glucose. On the other hand, if aquaporin-mediated water flow had been selectively abolished, Na⁺ sieving would not improve after raising the glucose concentration in the PD fluid.

Low UF Due to Increased (Lymphatic) and Interstitial Absorption of Fluid and Macromolecules from the Peritoneal Cavity

Figure 4(c) — Sodium sieving curves corresponding to the ultrafiltration curves presented in Figure 4(a) (3.86%/4.25% glucose). Note that changes in direct lymphatic absorption will not significantly change the pattern of sodium sieving (lower curves).

Figure 4(a) — Effects of simultaneously varying direct lymphatic absorption (L) and permeability surface area product (PS) for glucose on the ultrafiltration (UF) profile for 3.86%/4.25% glucose in the dialysis fluid. Upper curve denotes a perturbation of PS for glucose to 75% of control while maintaining L at 0.3 mL/min. Simultaneously increasing L to 1.0 mL/min and reducing PS for glucose to 75% from control (lower curve) will more or less have a cancelling effect on the UF profile for 3.86%/4.25% glucose, at least after 240 _ 300 minutes.

Figure 4(b) — Solid line indicates control ultrafiltration profile for 1.36%/1.5% glucose. Lower line depicts the scenario when PS for glucose has been reduced to 75% of control while direct lymphatic absorption increased from 0.3 mL/min to 1.0 mL/min. Long dwells, especially when dialysis fluid glucose concentration is kept low, will be particularly useful in revealing increases in lymphatic absorption.

In some patients, especially those with a large surface area (S), the rate of elimination of an intraperitoneal macromolecular volume marker (such as albumin or dextran) may be increased. Very few of these patients exhibit an increased rate of "direct" lymphatic absorption (L), that is, increased clearance of macromolecular tracer from dialysis fluid to plasma (121). In Figures 4(a) and 4(b), solid lines indicate the normal UF profile for 3.86%/4.25% and 1.36%/1.5% glucose, respectively, when the direct lymphatic absorption is 0.3 mL/min. To illustrate the usefulness of long dwells (e.g., overnight dwells) in revealing increases in direct lymphatic absorption, lymph flow has been perturbed from 0.3 to 1.0 mL/min concomitantly with a reduction in PS for glucose by 25% (to 0.75 of control). For comparison, the simulated curve for L = 0.3 mL/min and PS set at 75% of control value is also shown (upper curves in both figures). Note that, for 3.86%/4.25% glucose [Figure 4(a)], the effects of increasing L and reducing PS will cancel each other more or less completely. Up to at least 240 _ 300 minutes, the perturbed curve is identical to the control curve. However, for an overnight dwell using 1.36%/1.5% glucose, the increased direct lymphatic absorption will reduce the drained volume after 600 minutes by nearly 400 mL, even though PS for glucose is reduced [Figure 4(b)]. Thus, long dwells may be particularly useful in revealing UFF due to increases in direct lymphatic absorption, especially for "low" glucose dialysis fluid concentrations (2.27%/2.5% and 1.36%/1.5%).

In Figure 4(c) the Na⁺ curve corresponding to Figure 4(a) is depicted. Note that when PS for glucose is reduced, Na⁺ sieving is increased. However, when L is increased (from 0.3 to 1.0) there is almost no change in Na⁺ sieving when PS is kept constant.

Low UF Caused by a Severely Decreased Peritoneal Surface Area

This is probably a very rare cause of UF loss. In its extreme case, when the surface area (S) is minimal, there would be no fluid movement at all across the peritoneal membrane during the entire dwell, and the UF curve would become entirely flat. In Figure 1(a) the situation where S is reduced to 0.1 (PS and L_pS reduced to 0.1 of control) is shown as the lower line. Note, however, that for moderate reductions in surface area of the membrane (to 0.5 for example), time to curve maximum (t_peak) is increased while the curve "height" is only slightly reduced.

It can be concluded that the three-pore model of peritoneal transport represents a simple, yet detailed physical model of peritoneal exchange. This model has proved to have a good power in predicting UF profiles in the clinical setting. The simulations have clearly shown that increases in glucose MTAC, independently from increases in the UF coefficient, will result in marked UFF. This seems by far to be the most common cause of UF loss. When reductions occur in either the membrane UF coefficient (L_pS) or in the osmotic efficiency of glucose (the glucose reflection coefficient s_g), the glucose osmotic conductance will be reduced and UFF may ensue. The glucose osmotic conductance (L_pS × s_g) may thus fall due to either aquaporin failure or to reductions in the UF coefficient (independent of changes in PS for glucose). In clinical practice it may be cumbersome to distinguish between these two etiologies of reductions in L_pS × s_g. In the rather rare cases of UFF due to increases in lymphatic absorption, long dwells, especially overnight dwells, will often reveal this condition, particularly in patients who are low or low-average transporters.

Hopefully, the kind of simulations presented here will provide direction toward further investigations of the kind of UFF that sometimes occurs in, for example, long-term CAPD. Based on the computed results it may also be possible to design more detailed experiments in order to improve our understanding of UFF based on a great variety of other pathophysiological etiologies.

Acknowledgments

The studies performed by the authors and discussed in this paper were supported by the Dutch Kidney Foundation (Nierstichting Nederland), by the Swedish Medical Research Council (grant 08285), by grants from the Inga-Britt and Arne Lundberg Foundation, and by Baxter Healthcare. Kirstin Wikborg and Marion A. Zeeman are gratefully acknowledged for the skilful preparation of the manuscript.

Correspondence to: R.T. Krediet, Division of Nephrology, Department of Medicine, Academic Medical Center, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands.

REFERENCES

CLICK HERE for more References

1. Lysaght MJ, Farrell PC. Membrane phenomena and mass transfer kinetics in peritoneal dialysis. J Membr Sci 1989; 44:5_33.

2. Waniewski J. Mathematical models for peritoneal transport characteristics. Perit Dial Int (in press).

3. Rippe B, Stelin G. Simulations of peritoneal solute transport during CAPD. Application of two-pore formalism. Kidney Int 1989; 35:1234_44.

4. Stelin G, Rippe B. A phenomenological interpretation of the variation in dialysate volume with dwell time in CAPD. Kidney Int 1990; 38:465_72.

5. Rippe B, Stelin G, Haraldsson B. Computer simulations of peritoneal transport in CAPD. Kidney Int 1991; 40:315_25.

6. Flessner MF. Osmotic barrier of the parietal peritoneum. Am J Physiol 1994; 267 (Renal Fluid Electrolyte Physiol 36):F861_70.

7. Fox JR, Wayland H. Interstitial diffusion of macromolecules in the rat mesentery. Microvasc Res 1979; 18:255_76.

8. Flessner MF. Small solute transport across specific peritoneal tissue surfaces in the rat. J Am Soc Nephrol 1996; 7:225_233.

9. Zakaria ER, Carlsson O, Sjunnesson H, Rippe B. Liver is not essential for solute transport during peritoneal dialysis. Kidney Int 1996; 50:298_303.

10. Grotte G. Passage of dextran molecules across the blood-lymph barrier. Acta Chir Scand Suppl 1956; 211:1_84.

11. Mayerson HS, Wolfram CG, Shirley Jr HH, Wasserman K. Regional differences in capillary permeability. Am J Physiol 1960; 198:155_60.

12. Pannekeet MM, Mulder JB, Weening JJ, Struijk DG, Zweers MM, Krediet RT. Demonstration of aquaporin-chip in peritoneal tissue of uremic and CAPD patients. Perit Dial Int 1996; 16(Suppl 1):S54_7.

13. Akiba P, Ota T, Fushimi K, Tamura H, Hata T, Sasaki S, et al. Water channel AQP1, 3, and 4 in the human peritoneum and peritoneal dialysate. Adv Perit Dial 1997; 13:3_5.

14. Carlsson O, Nielsen S, Zakaria ER, Rippe B. In vivo inhibition of transcellular water channels (aquaporin1) during acute peritoneal dialysis in rats. Am J Physiol 1996; 271 (Heart Circ Physiol 40):H2254_62.

15. Henderson LW. Peritoneal ultrafiltration dialysis: enhanced urea transfer using hypertonic peritoneal dialysis fluid. J Clin Invest 1966; 45:950_5.

16. Nolph KD, Hano JE, Teschan PE. Peritoneal sodium transport during hypertonic peritoneal dialysis. Ann Intern Med 1969; 70:931_41.

17. Rubin J, Klein E, Bower JD. Investigation of the net sieving coefficient of the peritoneal membrane during peritoneal dialysis. ASAIO J 1982; 5:9_15.

18. Chen TW, Khanna R, Moore H, Twardowski ZJ, Nolph KD. Sieving and reflection coefficients for sodium salts and glucose during peritoneal dialysis. J Am Soc Nephrol 1991; 2:1092_100.

19. Rippe B, Perry MA, Granger DN. Permselectivity of the peritoneal membrane. Microvasc Res 1985; 29:89_102.

20. Krediet RT, Imholz ALT, Struijk DG, Koomen GCM, Arisz L. Ultrafiltration failure in continuous ambulatory peritoneal dialysis. Perit Dial Int 1993; 13(Suppl 2):S59_66.

21. Zakaria ER, Rippe B. Osmotic barrier properties of the rat peritoneal membrane. Acta Physiol Scand 1993; 149:355_64.

22. Imholz ALT, Koomen GCM, Struijk DG, Arisz L, Krediet RT. Fluid and solute transport in CAPD patients using ultralow sodium dialysate. Kidney Int 1994; 46:333_40.

23. Leypoldt JK. Interpreting peritoneal osmotic reflection coefficients using a distributed model of peritoneal transport. Adv Perit Dial 1993; 9:3_7.

24. Twardowski ZJ, Nolph KD, Khanna R, Prowant B, Ryan LP, Moore HL, et al. Peritoneal equilibration test. Perit Dial Bull 1987; 7:138_47.

25. Imholz ALT, Koomen GCM, Struijk DG, Arisz L, Krediet RT. The effect of dialysate osmolarity on the transport of low molecular weight solutes and proteins during CAPD. Kidney Int 1993; 43:1339_46.

26. Nolph KD, Ghods A, Brown P, Miller F, Harris P, Pyle K, et al. Effects of nitroprusside on peritoneal mass transfer coefficients and microvascular physiology. ASAIO Trans 1977; 23:210_18.

27. Renkin EM. Control of microcirculation and blood-tissue exchange. In: Renkin EM, Michel CC, eds. Handbook of physiology. The cardiovascular system. Vol. 4. Washington, D.C.: American Physiological Society 1984:627_87.

28. Miller FN, Joshua IG, Harris PD, Wiegman DL, Jauchem JR. Peritoneal dialysis solutions and the microcirculation. Contrib Nephrol 1979; 17:51_8.

29. Pietrzak I, Hirszel P, Shostak A, Welch PG, Lee RE, Maher JF. Splanchnic volume, not flow rate, determines peritoneal permeability. ASAIO Trans 1989; 35:583_7.

30. Wang T, Heimbürger O, Waniewski J, Bergström J, Lindholm B. Increased peritoneal permeability is associated with decreased fluid and small-solute removal and higher mortality in CAPD patients. Nephrol Dial Transplant 1998; 13:1242_9.

31. Rose BD. Clinical physiology of acid-base and electrolyte disorders. 2nd ed. New York: McGraw-Hill, 1984:33.

32. Imholz ALT, Koomen GCM, Struijk DG, Arisz L, Krediet RT. The effect of an increased intraperitoneal pressure on fluid and solute transport during CAPD. Kidney Int 1993; 44:1078_85.

33. Twardowski ZJ, Khanna R, Nolph KD, Scalamogna A, Metzler MH, Schneider TW, et al. Intra-abdominal pressures during natural activities in patients treated with continuous ambulatory peritoneal dialysis. Nephron 1986; 44:129_35.

34. Twardowski ZJ, Prowant BF, Nolph KD, Martinez AJ, Lampton LM. High volume, low frequency continuous ambulatory peritoneal dialysis. Kidney Int 1983; 23:64_70.

35. Krediet RT, Koomen GCM, Struijk DG, van Olden RW, Imholz ALT, Boeschoten EW. Practical methods for assessing dialysis efficiency during peritoneal dialysis. Kidney Int 1994; 46(Suppl 48):S7_13.

36. Ho-dac-Pannekeet MM, Schouten N, Langedijk MJ, Hiralall JK, de Waart DR, Struijk DG, et al. Peritoneal transport characteristics with glucose polymer based dialysate. Kidney Int 1996; 50:979_86.

37. Pannekeet MM, Imholz ALT, Struijk DG, Koomen GCM, Langedijk MJ, Schouten N, et al. The standard peritoneal permeability analysis: a tool for the assessment of peritoneal permeability characteristics in CAPD patients. Kidney Int 1995; 48:866_75.

38. Heimbürger O, Waniewski J, Werynski A, Lindholm B. A quantitative description of solute and fluid transport during peritoneal dialysis. Kidney Int 1992; 41:1320_32.

39. Krediet RT, Boeschoten EW, Zuyderhoudt FMJ, Arisz L. The relationship between peritoneal glucose absorption and body fluid loss by ultrafiltration during continuous ambulatory peritoneal dialysis. Clin Nephrol 1987; 27:51_5.

40. Alsop RM. History, chemical and pharmaceutical development of icodextrin. Perit Dial Int 1994; 14(Suppl 2):S5_12.

41. Mistry CD, Gokal R. Can ultrafiltration occur with a hypo-osmolar solution in peritoneal dialysis? The role for "colloid" osmosis. Clin Sci 1993; 85:495_500.

42. Rippe B, Levin L. Computer simulations of ultrafiltration profiles for an icodextrin-based peritoneal fluid in CAPD. Kidney Int 2000; 57:2546_56.

43. Douma CE, de Waart DR, Struijk DG, Krediet RT. Effect of amino acid based dialysate on peritoneal blood flow and permeability in stable CAPD patients: a potential role for nitric oxide? Clin Nephrol 1996; 45:295_302.

44. Rubin J, Nolph KD, Popovich RP, Moncrief JW, Prowant B. Drainage volumes during continuous ambulatory peritoneal dialysis. ASAIO J 1997; 2:54_60.

45. Canaud B, Liendo_Liendo C, Claret G, Mion H, Mion C. Etude "in situ" de la cinétique de l'ultrafiltration en cours de dialyse peritoneale avec périodes de diffusion prolongée. Néphrologie 1980; 1:126_32.

46. Douma CE, Hiralall JK, De Waart DR, Struijk DG, Krediet RT. Icodextrin with nitroprusside increases ultrafiltration and peritoneal transport during long CAPD dwells. Kidney Int 1998; 53:1014_21.

47. Heimbürger O, Waniewski J, Werynski A, Tranæus A, Lindholm B. Peritoneal transport in CAPD patients with permanent loss of ultrafiltration capacity. Kidney Int 1990; 38:495_506.

48. Mactier RA, Khanna R, Twardowski ZJ, Moore H, Nolph KD. Contribution of lymphatic absorption to loss of ultrafiltration and solute clearances in continuous ambulatory peritoneal dialysis. J Clin Invest 1987; 80:1311_16.

49. Krediet RT, Struijk DG, Koomen GCM, Arisz L. Peritoneal fluid kinetics during CAPD measured with intraperitoneal dextran 70. ASAIO Trans 1991; 37:662_7.

50. Rippe B, Stelin G, Ahlmen J. Lymph flow from the peritoneal cavity in CAPD patients. In: Maher JF, Winchester JF, eds. Frontiers in peritoneal dialysis. New York: Field and Rich, 1986:24_30.

51. Wang T, Chen C, Heimbürger O, Waniewski J, Bergström J, Lindholm B. Hyaluronan decreases peritoneal fluid absorption in peritoneal dialysis. J Am Soc Nephrol 1997; 8:1915_20.

52. Flessner MF, Fenstermacher JD, Dedrick RL, Blasborg RG. Peritoneal absorption of macromolecules studied by quantitative autoradiography. Am J Physiol 1985; 248:H26_32.

53. Kaysen GA, Schoenfeld PY. Albumin homeostasis in patients undergoing continuous ambulatory peritoneal dialysis. Kidney Int 1984; 25:107_14.

54. Zakaria ER, Rippe B. Peritoneal fluid and tracer albumin kinetics in the rat. Effects of increases in intraperitoneal hydrostatic pressure. Perit Dial Int 1995; 15:118_28.

55. Krediet RT, Boeschoten EW, Struijk DG, Arisz L. Differences in the peritoneal transport of water, solutes and proteins between dialysis with two- and with three-litre exchanges. Nephrol Dial Transplant 1988; 2:198_204.

56. Imholz ALT, Koomen GCM, Voorn WJ, Struijk DG, Arisz L, Krediet RT. Day-to-day variability of fluid and solute transport in upright and recumbent positions during CAPD. Nephrol Dial Transplant 1998; 13:146_53.

57. Mactier RA, Khanna R, Twardowski ZJ, Moore H, Nolph KD. Influence of phosphatidylcholine on lymphatic absorption during peritoneal dialysis in the rat. Perit Dial Int 1988; 8:179_86.

58. Struijk DG, van der Reijden HJ, Krediet RT, Koomen GCM, Arisz L. Effect of phosphatidylcholine on peritoneal transport and lymphatic absorption in a CAPD patient with sclerosing peritonitis. Nephron 1989; 51:577_8.

59. Struijk DG, Krediet RT, Koomen GCM, Boeschoten EW, van der Reijden HJ, Arisz L. Indirect measurement of lymphatic absorption with inulin in continuous ambulatory peritoneal dialysis (CAPD) patients. Perit Dial Int 1990; 10:141_5.

60. Krediet RT, Struijk DG, Boeschoten EW, Hoek FJ, Arisz L. Measurement of intraperitoneal fluid kinetics in CAPD patients by means of autologous hemoglobin. Neth J Med 1988; 33:281_90.

61. Krediet RT, Struijk DG, Koomen GCM, Hoek FJ, Arisz L. The disappearance of macromolecules from the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD) is not dependent on molecular size. Perit Dial Int 1990; 10:147_52.

62. Kruse M, Mahiout A, Kliem V, Kurz P, Koch KM, Brunkhorst R. Interleukin-1b stimulates glucose uptake of human peritoneal mesothelial cells. Perit Dial Int 1996; 16(Suppl 1):S58_60.

63. Schröppel B, Fischereder M, Wiese P, Segerer S, Huber S, Kretzler M, et al. Expression of glucose transporters in human peritoneal mesothelial cells. Kidney Int 1998; 53:1278_87.

64. Waniewski J, Heimbürger O, Werynski A, Lindholm B. Aqueous solute concentrations and evaluation of mass transport coefficients in peritoneal dialysis. Nephrol Dial Transplant 1992; 7:50_6.

65. Nolph KD, Twardowski ZJ, Popovich RP, Rubin J. Equilibration of peritoneal dialysis solutions during long-dwell exchanges. J Lab Clin Med 1979; 93:246_56.

66. Wang T, Waniewski J, Heimbürger O, Werynski A, Lindholm B. A quantitative analysis of sodium transport and removal during peritoneal dialysis. Kidney Int 1997; 52:1609_16.

67. Raja RM, Cantor RE, Boreyko C, Bushehri H, Kramer MS, Rosenbaum JL. Sodium transport during ultrafiltration peritoneal dialysis. ASAIO Trans 1972; 18:429_33.

68. Leypoldt JK, Charney DI, Cheung AK, Naprestek CL, Akin BH, Shockley TR. Ultrafiltration and solute kinetics using low sodium peritoneal dialysate. Kidney Int 1995; 48:1959_66.

69. Marfis L, Serkes KD, Nolph KD. Calcium carbonate as a phosphate binder: is there a need to adjust peritoneal calcium concentrations in patients using CaCO₃? Perit Dial Int 1989; 9:325_8.

70. Rippe B, Levin L. Should dialysate calcium be varied in proportion to the amount of ultrafiltration in peritoneal dialysis dwells? Directions from a computer simulation. Perit Dial Int 1998; 18:474_7.

71. Blake PG, Somolas K, Izatt S, Oreopoulos DG. A highly permeable peritoneal membrane is an adverse risk factor in CAPD. Clin Invest Med 1991; 14:127.

72. Heaf J. CAPD adequacy and dialysis morbidity: detrimental effect of a high peritoneal equilibration rate. Ren Fail 1995; 17:575_87.

73. Davies SJ, Bryan J, Phillips L, Russell GI. The predictive value of KT/V and peritoneal solute transport in CAPD patients is dependent on the type of comorbidity present. Perit Dial Int 1996; 16(Suppl 1):S158_62.

74. Wu C, Huang C, Huang J, Wu M, Leu M. High flux peritoneal membrane is a risk factor in survival of CAPD treatment. Adv Perit Dial 1996; 12:105_9.

75. Churchill DN, Thorpe KE, Nolph KD, Keshaviah PR, Oreopoulos DG, Pagé D. Increased peritoneal membrane transport is associated with decreased patient and technique survival for continuous peritoneal dialysis patients. J Am Soc Nephrol 1998; 9:1285_92.

76. Wang T, Waniewski J, Heimbürger O, Bergström J, Werynski A, Lindholm B. A simple and fast method to estimate peritoneal membrane transport characteristics using dialysate sodium concentration. Perit Dial Int (in press).

77. Blake P, Burkart JM, Churchill DN, Daugirdas J, Depner T, Hamburger RJ, et al. Recommended clinical practices for maximizing peritoneal dialysis clearances. Perit Dial Int 1996; 16:448_56.

78. Keshaviah P, Emerson PF, Vonesh EF, Brandes JC. Relationship between body size, fill volume and mass transfer area coefficient in peritoneal dialysis. J Am Soc Nephrol 1994; 4:1820_6.

79. Wang T, Heimbürger O, Cheng H, Waniewski J, Bergström J, Lindholm B. Effects of dialysate fill volume on peritoneal fluid and solute transport. Kidney Int 1997; 52:1068_76.

80. Wang T, Cheng H, Heimbürger O, Waniewski J, Bergström J, Lindholm B. Hyaluronan prevents the decrease in net fluid removal caused by increased dialysate fill volume. Kidney Int 1998; 53:496_502.

81. Zhu Q, Carlsson O, Rippe B. Clearance of tracer albumin from peritoneal cavity to plasma at low intraperitoneal volumes and hydrostatic pressures. Perit Dial Int 1998; 18:497_504.

82. Drake RE, Gabel JC. Diaphragmatic lymph vessel drainage of the peritoneal cavity. Blood Purif 1992; 10:132_5.

83. Raja RM, Kramer MS, Rosenbaum JL, Bolisay C, Krug M. Contrasting changes in solute transport and ultrafiltration with peritonitis in CAPD patients. ASAIO Trans 1981; 27:68_70.

84. Rubin J, Ray R, Barnes T, Bower J. Peritoneal abnormalities during infectious episodes of continuous ambulatory peritoneal dialysis. Nephron 1981; 29:124_7.

85. Rubin J, McFarland S, Hellems EW, Bower JD. Peritoneal dialysis during peritonitis. Kidney Int 1981; 19:460_4.

86. Raja RM, Kramer MS, Barber K. Solute transport and ultrafiltration during peritonitis in CAPD patients. ASAIO J 1984; 7:8_11.

87. Krediet RT, Zuyderhoudt MJ, Boeschoten EW, Arisz L. Alterations in the peritoneal transport of water and solutes during peritonitis in continuous ambulatory peritoneal dialysis patients. Eur J Clin Invest 1987; 17:43_52.

88. Verger C, Luger A, Moore HL, Nolph KD. Acute changes in peritoneal transport properties with infectious peritonitis and mechanical injury. Kidney Int 1983; 23:823_31.

89. Douma CE, de Waart DR, Struijk DG, Krediet RT. Are phospholipase A₂ and nitric oxide involved in the alterations in peritoneal transport during CAPD peritonitis? J Lab Clin Med 1998; 132:329_40.

90. Widerøe TE, Smeby LC, Mjåland S, Dahl K, Berg LJ, Aas TW. Long-term changes in transperitoneal water transport during continuous ambulatory peritoneal dialysis. Nephron 1984; 38:238_47.

91. Zemel D, Betjes MGH, Dinkla C, Struijk DG, Krediet RT. Analysis of inflammatory mediators and peritoneal permeability to macromolecules shortly before the onset of overt peritonitis in patients treated with CAPD. Perit Dial Int 1995; 15:134_41.

92. Krediet RT, Arisz L. Fluid and solute transport across the peritoneum during continuous ambulatory peritoneal dialysis (CAPD). Perit Dial Int 1989; 9:15_25.

93. Haraldsson B. Assessing the peritoneal dialysis capacities of individual patients. Kidney Int 1995; 47:1187_98.

94. Blumenkrantz MJ, Gahl GM, Kopple JD, Kamdar AV, Jones MR, Kessel M, et al. Protein losses during peritoneal dialysis. Kidney Int 1981; 19:593_602.

95. Steinhauer HB, Schollmeyer P. Prostaglandin-mediated loss of proteins during peritonitis in continuous ambulatory peritoneal dialysis. Kidney Int 1986; 29:584_90.

96. Zemel D, Koomen GCM, Hart AAM, ten Berge RJM, Struijk DG, Krediet RT. Relationship of TNF-a, interleukin-6 and prostaglandins to peritoneal permeability for macromolecules during longitudinal follow-up of peritonitis in continuous ambulatory peritoneal dialysis. J Lab Clin Med 1993; 122:686_96.

97. Zemel D, Struijk DG, Dinkla C, Stolk LM, ten Berge RJM, Krediet RT. Effects of intraperitoneal cyclooxygenase inhibition on inflammatory mediators in dialysate and peritoneal membrane characteristics during peritonitis in continuous ambulatory peritoneal dialysis. J Lab Clin Med 1995; 126:204_15.

98. Douma CE, de Waart DR, Struijk DG, Krediet RT. The nitric oxide donor nitroprusside intraperitoneally affects peritoneal permeability in CAPD. Kidney Int 1997; 51:1885_92.

99. Gokal R, Jakubowski C, King J, Hunt L, Bogle S, Baillard R, et al. Outcome in patients on continuous ambulatory peritoneal dialysis: 4 year analysis of a prospective multicentre study. Lancet 1987; 2:1105_8.

100. CANUSA Peritoneal Dialysis Study Group. Adequacy of dialysis and nutrition in continuous ambulatory peritoneal dialysis: association with clinical outcomes. J Am Soc Nephrol 1996; 7:198_207.

101. Genestier J, Hedelin G, Schaffer P, Faller B. Prognostic factors in CAPD patients: a retrospective study of a 10-year period. Nephrol Dial Transplant 1995; 10: 1905_11.

102. Krediet RT, Douma CE, van Olden RW, Ho-dac-Pannekeet MM, Struijk DG. Augmenting solute clearance in peritoneal dialysis. Kidney Int 1998; 54:2218_35.

103. Kawaguchi Y, Hasegawa T, Nakayama M, Kubo H, Shigematu T. Issues affecting the longevity of the continuous peritoneal dialysis therapy. Kidney Int 1997; 52(Suppl 62):S105_7.

104. Ho-dac-Pannekeet MM, Atasever B, Struijk DG, Krediet RT. Analysis of ultrafiltration failure in peritoneal dialysis patients by means of standard peritoneal permeability analysis. Perit Dial Int 1997; 17:144_50.

105. Rippe B. How to measure ultrafiltration failure: 2.27% or 3.86% glucose? Perit Dial Int 1997; 17:125_8.

106. Virga G, Amici G, DaRin G, Vianello A, Calconi G, Da Porto A, et al. Comparison of fast peritoneal equilibration test with 1.36 and 3.86% dialysis solutions. Blood Purif 1994; 12:113_20.

107. Krediet RT, Boeschoten EW, Zuyderhoudt FMJ, Arisz L. Peritoneal transport characteristics of water, low molecular weight solutes and proteins during long-term continuous ambulatory peritoneal dialysis. Perit Dial Bull 1986; 6:61_5.

108. Davies SJ, Brown B, Bryan J, Russell GI. Clinical evaluation of the peritoneal equilibration test: a population-based study. Nephrol Dial Transplant 1993; 8:64_70.

109. Heimbürger O, Waniewski J, Werynski A, Park MS, Lindholm B. Dialysate to plasma concentration (D/P) versus peritoneal transport parameters in CAPD. Nephrol Dial Transplant 1994; 9:47_59.

110. Monquil MCJ, Imholz ALT, Struijk DG, Krediet RT. Does impaired transcellular water transport contribute to net ultrafiltration failure during CAPD? Perit Dial Int 1995; 15:42_8.

111. Zweers MM, Struijk DG, Krediet RT. Correcting sodium sieving for diffusion from circulation. Adv Perit Dial 1999; 15:65_72.

112. Smit W, Langedijk MJ, Schouten N, van den Berg N, Struijk DG, Krediet RT. A comparison between 1.36% and 3.86% glucose dialysis solutions for the assessment of peritoneal membrane function. Perit Dial Int (in press).

113. Verger C, Larpent L, Celicout B. Clinical significance of ultrafiltration failure on CAPD. In: La Greca G, Chiaramonte S, Fabris A, Feriani M, Ronco C, eds. Peritoneal dialysis. Milan: Wichtig Editore, 1986:91_4.

114. Krediet RT, Struijk DG, Boeschoten EW, Koomen GCM, Stouthard JML, Hoek FJ, et al. The time course of peritoneal transport kinetics in continuous ambulatory peritoneal dialysis patients who develop sclerosing peritonitis. Am J Kidney Dis 1989; 13:299_307.

115. Waniewski J, Heimbürger O, Werynski A, Lindholm B. Osmotic conductance of the peritoneum in CAPD patients with permanent loss of ultrafiltration capacity. Perit Dial Int 1996; 16:488_96.

116. Slingeneyer A, Canaud B, Mion C. Permanent loss of ultrafiltration capacity of peritoneum in long-term peritoneal dialysis. Nephron 1983; 33:133_8.

117. Ho-dac-Pannekeet MM, Koopmans JG, Struijk DG, Krediet RT. Restriction coefficients of low molecular weight solutes and macromolecules during peritoneal dialysis. Adv Perit Dial 1997; 13:17_22.

118. Struijk DG, Krediet RT, Koomen GCM, Hoek FJ, Boeschoten EW, van der Reijden HJ, et al. Functional characteristics of the peritoneal membrane in long-term continuous ambulatory peritoneal dialysis. Nephron 1991; 59:213_20.

119. Goffin E, Combet S, Jamar F, Cosyns J-P, Devuyst O. Expression of aquaporin-1 (AQP1) in a long-term peritoneal dialysis patient with impaired transcellular water transport. Am J Kidney Dis 1999; 33:383_8.

120. Krediet RT. Loss of membrane permeability: a threat for CAPD. In: Andreucci VE, Fine LG, eds. International yearbook of nephrology 1997. New York: Oxford University Press, 1997:153_62.

121. Heimbürger O, Waniewski J, Werynski A, Park MS, Lindholm B. Lymphatic absorption in CAPD patients with permanent loss of ultrafiltration capacity. Blood Purif 1995; 13:327_39.

122. Verger C, Celicout B. Peritoneal permeability and encapsulating peritonitis. Lancet 1985; 1:986_7.

123. Gotloib L, Shostak A, Bar-Shella P, Cohen R. Continuous mesothelial injury and regeneration during long-term peritoneal dialysis. Perit Dial Int 1987; 7:148_55.

124. Pannekeet MM, Zemel D, Koomen GCM, Struijk DG, Krediet RT. Dialysate markers of peritoneal tissue during peritonitis and in stable CAPD. Perit Dial Int 1995; 15:217_25.

125. Hagmolen of ten Have W, Ho-dac-Pannekeet MM, Struijk DG, Krediet RT. Mesothelial regeneration after peritonitis in dialysis patients. J Am Soc Nephrol 1997; 8:180A.

126. Struijk DG, Krediet RT, Koomen GCM, Boeschoten EW, Hoek FJ, Arisz L. A prospective study of peritoneal transport in CAPD patients. Kidney Int 1994; 45: 1739_44.

127. Andreoli SP, Langefeld CD, Stadler S, Smith P, Sears A, West K. Risks of peritoneal membrane failure in children undergoing long-term peritoneal dialysis. Pediatr Nephrol 1993; 7:543_7.

128. Oulès R, Challah S, Brunner FP. Case-control study to determine the cause of sclerosing peritoneal disease. Nephrol Dial Transplant 1988; 3:66_9.

129. Hendriks PMEM, Ho-dac-Pannekeet MM, van Gulik TM, Struijk DG, Phoa SSKS, Sie L, et al. Peritoneal sclerosis in chronic peritoneal dialysis patients: analysis of clinical presentation, risk factors, and peritoneal transport kinetics. Perit Dial Int 1997; 17:136_43.

130. Selgas R, Fernandez_Reyes MJ, Bosque E, Bajo M-A, Borrego F, Jimenez C, et al. Functional longevity of the human peritoneum: how long is continuous peritoneal dialysis possible? Results of a prospective medium long-term study. Am J Kidney Dis 1994; 23:64_73.

131. Davies SJ, Bryan J, Phillips L, Russell GI. Longitudinal changes in peritoneal kinetics: the effects of peritoneal dialysis and peritonitis. Nephrol Dial Transplant 1996; 11:498_506.

132. Krediet RT. Preserving the integrity of the peritoneal membrane in chronic peritoneal dialysis. Kidney Int 1999; 55:341_56.

133. Gotloib L, Shostak A, Waysbrot V. Detrimental effects of peritoneal dialysis solutions upon in vivo and in situ exposed mesothelium. Perit Dial Int 1997; 17(Suppl 2):S13_16.

134. Di Paolo N, Sacchi G. Peritoneal vascular changes in continuous ambulatory peritoneal dialysis (CAPD): an in vivo model for the study of diabetic microangiopathy. Perit Dial Int 1989; 9:41_5.

135. Mateijsen MAM, van der Wal AC, Hendriks PMEM, Zweers MM, Mulder J, Krediet RT. Vascular and interstitial changes in the peritoneum of CAPD patients with peritoneal sclerosis. Perit Dial Int 1999; 19: 517_25.

136. Honda K, Nitta K, Horita S, Yumura W, Nikei W. Morphological changes in the peritoneal vasculature of patients on CAPD with ultrafiltration failure. Nephron 1996; 72:171_6.

137. Zweers MM, Mulder JB, Krediet RT, Struijk DG. Vascular and interstitial changes in a continuous peritoneal infusion model in the rat. J Am Soc Nephrol 1998; 9:195A.

138. Yamada K, Miyakasa Y, Hamaguchi K, Nakayama M, Nakano H, Nozaki O, et al. Immunohistochemical study of human advanced glycosylation end products (AGE) in chronic renal failure. Clin Nephrol 1994; 42:354_61.

139. Nakayama M, Kawaguchi Y, Yamada K, Hasegawa T, Takazoe K, Katok N, et al. Immunohistochemical detection of advanced glycosylation end products in the peritoneum and its possible pathophysiological role in CAPD. Kidney Int 1997; 51:182_6.

140. Ferrara N. Vascular endothelial growth factor. The trigger for neovascularization in the eye. Lab Invest 1995; 72:615_18.

141. Sharma K, Ziyadeh FN. Hyperglycemia and diabetic kidney disease. The call for transforming growth factor-b as a key mediator. Diabetes 1995; 44:1139_46.

142. Zweers MM, de Waart DR, Struijk DG, Krediet RT. The growth factors VEGF and TGF-b1 in peritoneal dialysis. J Lab Clin Med 1999; 134:124_32.

143. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shak ST, et al. Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 1994; 331:1480_7.

144. Tanaka Y, Katoh S, Hori S, Miura M, Yamashita H. Vascular endothelial growth factor in diabetic retinopathy. Lancet 1997; 349:1520.

145. Struijk DG, Krediet RT, Imholz ALT, Koomen GCM, Arisz L. Fluid kinetics in CAPD patients during dialysis with a bicarbonate-based hypoosmolar solution. Blood Purif 1996; 14:217_26.

146. Daugirdas JT, Ing TS, Gandhi VC, Hano JE, Chen WT, Yuan T. Kinetics of peritoneal fluid absorption in patients with chronic renal failure. J Lab Clin Med 1980; 95:351_61.

147. Henderson LW, Nolph KD. Altered permeability of the peritoneal membrane after using hypertonic peritoneal dialysis fluid. J Clin Invest 1969; 48: 992_1001.

148. Krediet RT, Boeschoten EW, Zuyderhoudt FMJ, Strackee J, Arisz L. Simple assessment of the efficacy of peritoneal transport in continuous ambulatory peritoneal dialysis patients. Blood Purif 1986; 4:194_203.

149. Waniewski J, Werynski A, Heimbürger O, Lindholm B. Simple models for description of small-solute transport in peritoneal dialysis. Blood Purif 1991; 9:129_41.

150. Waniewski J, Werynski A, Heimbürger O, Lindholm B. A comparative analysis of mass transport models in peritoneal dialysis. ASAIO Trans 1991; 37:65_75.

151. Waniewski J, Heimbürger O, Werynski A, Park MS, Lindholm B. Diffusive and convective solute transport in peritoneal dialysis with glucose as an osmotic agent. Artif Organs 1995; 19:295_306.

152. Lindholm B, Werynski A, Bergström J. Kinetics of peritoneal dialysis with glycerol and glucose as osmotic agents. ASAIO J 1983; 6:131_7.

153. Vonesh EF, Rippe B. Net fluid absorption under membrane transport models of peritoneal dialysis. Blood Purif 1992; 10:209_26.

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Ultrafiltration Management in Peritoneal Dialysis Peritoneal Dialysis International, Vol. 20, Suppl. 4 Printed in Canada. All rights reserved.

0896-8608/00 $3.00 + .00 Copyright © 2000 International Society for Peritoneal Dialysis

Transport of Urea and Creatinine

Physiology of Fluid Transport

Pressure Gradients Across the Peritoneal Membrane During Peritoneal Dialysis

Pressure Gradients Across the Peritoneal Membrane During Peritoneal Dialysis Using 7.5% Icodextrin

Glucose and Sodium Transport

Glucose and Na+ Transport in Relation to Peritoneal Permeability Characteristics

Peritoneal Transport with Different Fill Volumes

Peritoneal Transport During Peritonitis

Failure of the Peritoneal Membrane

Investigations of Ultrafiltration Failure

Assessment of Aquaporin-Mediated Water Transport

Causes of Ultrafiltration Failure