Studies on the urinary excretion of thromboxane B2 in Zellweger patients and control subjects: evidence for a major role for peroxisomes in the beta-oxidative chain-shortening of thromboxane B2.

In this paper we studied the urinary excretion of thromboxane B2 and its beta-oxidation product 2,3-dinor-thromboxane B2 in urines from control subjects and four Zellweger patients, which lack morphologically distinguishable peroxisomes. In the urine of three classical Zellweger patients we found a ratio of 2,3-dinor-thromboxane B2/thromboxane B2 of 0.35, 0.48 and 0.62 respectively, whereas in healthy children and adults values were found of 3.1-10 and 5.5-40 respectively. These data strongly suggest that peroxisomes are a major site for beta-oxidation of thromboxane B2.

Isolation, identification, and analysis of 4-acetylaminophenol-glucuronide in body fluids of dialyzed renal patients; a molecular mass marker for peritoneal diffusive transport.

A noncharacteristic solute, appearing in gradient elution liquid chromatography (HPLC) profiles of body fluids of dialyzed renal patients, was isolated and identified by preparative HPLC, beta-glucuronidase induced enzymatic peak shift, and mass spectrometry. The compound was shown to be p-acetylaminophenol ('paracetamol')-glucuronide (PG). Serum and peritoneal dialysate PG concentrations were determined in a number of patients. Cuprophan in vivo dialyzer clearances were calculated. Peritoneal membrane mass transfer coefficients (MTC) of PG were calculated and compared with those of molecular mass markers for peritoneal diffusive mass transport studies (urea, creatinine, uric acid, and inulin). By extrapolation of an MTC versus molecular mass calibration line for urea, creatinine, and uric acid it is shown that PG behaves as expected from its molecular mass. We suggest that PG (Mr = 327) is suitable as a molecular mass marker for the molecular mass range between Mr 200 and 500. It may also be used as a marker for diffusive solute transport in hemodialysis treatment. The HPLC gradient elution technique used here appears to be suitable for the simultaneous analysis of the molecular mass markers creatinine, uric acid, and paracetamolglucuronide.

Dialysate CA125 in stable CAPD patients: no relation with transport parameters.

We investigated dialysate CA125 concentrations (dCA125) and its possible relation to transport parameters in 67 stable CAPD patients. dCA125 can be regarded as a reflection of mesothelial cell mass or mesothelial cell turn-over. In every patient a standard peritoneal permeability analysis (SPA) was done. dCA125 was determined in the effluent of all SPA's. The examinations were done during a 4 h dwell with glucose 1.36%. In 29 tests dextran 70(milligrams) was added for fluid kinetics. dCA125 was positively related to age (p = 0.03) and negatively to the duration of CAPD (p = 0.0003). No correlation existed with peritonitis incidence (p = 0.21). Also, no relationship was present with the mass transfer area coefficient of creatinine, or with net ultrafiltration. The intrinsic permeability to macromolecules, expressed as the restriction coefficient (rc) was also not related to dCA125 (p = 0.14). Data on fluid kinetics showed that neither transcapillary ultrafiltration rate, effective lymphatic absorption rate, the change in intraperitoneal volume (delta IPV) nor glucose absorption were related to dCA125. A subgroup of patients (n = 20) had low CA125 values (< 11 U/ml). They were treated with CAPD for a longer period of time (23 vs 16 months, p = 0.02), and had a higher rc (2.59 vs 2.23, p < 0.0001). The relationship between low dCA125 and duration of CAPD can possibly be explained by vanishing of the mesothelial layer, as has been reported in patients on long-term CAPD. The higher rc of the low dCA125 group is probably also related to duration of CAPD, and not directly to the mesothelial cell mass, as the mesothelium is no osmotic barrier and because no pathophysiological mechanism can explain the relationship between a low mesothelial cell mass and a low permeability to macromolecules. It can be concluded that mesothelial cell mass is negatively related to the duration of CAPD treatment, but mesothelial cells are unlikely to play an important role in transport kinetics.

Contribution of tubular anion and cation secretion to residual renal function in chronic dialysis patients.

The clearance of organic ions by the tubules may contribute to the removal of uremic waste products in dialysis patients. The renal excretion of an exogenous anion p-aminohippurate (PAH) was investigated in 10 peritoneal dialysis patients and 10 hemodialysis patients during one clearance period and compared with the clearance of creatinine (Ccr) and inulin (CIn). The clearance period was 24 hours in the peritoneal dialysis patients and one interdialytic interval of 3 days divided in 4 parts [CPA-D] in hemodialysis patients. In peritoneal dialysis patients the renal clearance of total PAH (median 14.3 ml/min, range 3.8-33.0) exceeded the CIN (median 3.2 ml/min, range 1.6-11.2, p < 0.005) and Ccr (median 4.0 ml/min, range 1.7-15.0, p < 0.005). A positive correlation was found between the tubular clearances of creatinine (cationic pathway) and of total PAH (anionic pathway, r: 0.72, p <0.02). In hemodialysis patients the clearance of total PAH (CPA: median 2.0, range 0.8-9.6; CPD: median 3.8, range 1.7-15.4) also exceeded the clearance of inulin (CPA: median 1.5, range 0.2-3.4; CPD: median 2.7, range 0.9-4.4) in the beginning and the end of the interdialytic interval (p < 0.005). The CIN and the clearance of total PAH increased during the interdialytic interval, but the Ccr (CPA: median 2.2, range 0.4-8.9, CPD: median 2.9, range 1.2-4.6) remained stable. Thus, the change in tubular clearance of creatinine and PAH was opposite during the interdialytic interval: it increased for total PAH and decreased for creatinine. The CTPAH/CIN ratio in hemodialysis patients was lower than in peritoneal dialysis patients. In CPA it was median 1.6 (range 1.1-5.6, p < 0.05) and in CPD it was median 1.7 (range 1.1-5.0, p < 0.02) and in the peritoneal dialysis patients it was median 3.6 (range 1.5-9.1). We conclude that tubular clearances contribute to the residual renal function in dialysis patients, but the tubular handling of anions and cations in relation to the residual GFR is different between peritoneal and hemodialysis patients. A difference in clearance of organic acids caused by the dialysis techniques may be an explanation for the differences in clinical outcome between the two dialysis modalities.

Interleukin-6 in CAPD patients without peritonitis: relationship to the intrinsic permeability of the peritoneal membrane.

We investigated whether day to day changes in the transport characteristics of the peritoneal membrane to macromolecules in patients treated with CAPD, were related to the levels of interleukin-6 (IL-6) in the effluent of an overnight dwell. Four stable CAPD patients without peritonitis collected all "nightbags" on consecutive days during 2 months for the determination of peritoneal IgG clearance. Serum samples were obtained weekly. IL-6 was determined in the effluent on all occasions where the IgG clearance was less than mean - SD or greater than mean + SD. On these days clearances of beta 2-microglobulin, albumin and alpha 2-macroglobulin were determined as well, to calculate the peritoneal restriction coefficient, i.e. the slope of the power relationship between protein clearances and their free diffusion coefficient in water. This coefficient was used as a parameter of the intrinsic permeability of the membrane. IL-6 was measured by a sensitive and specific bioassay, using the B13.29, subclone 9.9 hybridoma cell assay. Dialysate IL-6 was measured on 43 occasions when IgG clearance was high and on 37 occasions when IgG clearance was low. In all 4 patients indirect evidence was found for local production of IL-6 within the peritoneal cavity: mean dialysate/serum ratios were 15 to 452 times higher than could be expected when IL-6 would enter the dialysate by diffusion only. The patient with the highest dialysate/serum ratio showed higher clearances of albumin, IgG and alpha 2-macroglobulin than the other 3 patients (p less than 0.001) and a lower restriction coefficient (p less than 0.001), indicating a high intrinsic permeability.(ABSTRACT TRUNCATED AT 250 WORDS)

The disappearance of macromolecules from the peritoneal cavity during continuous ambulatory peritoneal dialysis (CAPD) is not dependent on molecular size.

The transport of macromolecules from the circulation to the peritoneal cavity is a size-selective restricted process, while the transport of these solutes from the peritoneal cavity is probably mainly by lymphatic absorption. If so, it should be independent of molecular size. Therefore, we studied with a clearance technique the disappearance of intraperitoneally administered inulin and polydisperse dextran 70 in nine continuous ambulatory peritoneal dialysis (CAPD) patients and compared the results with the simultaneously measured appearance clearance of serum proteins. Using gel permeation chromatography 18 dextran fractions with different molecular radii could be analyzed. Inulin clearance (2.94 mL/min) was higher than total dextran clearance (1.30 mL/min). The maximal dextran concentration in all dialysate samples was found in the 50.4 A fraction. The clearances of the dextran fractions were the same of different molecular sizes. All disappearance clearances were higher than the appearance clearances: the protein/dextran clearance ratio ranged from 0.15 for albumin/36 A to 0.04 for alpha 2-macroglobulin/91 A. This confirms that the appearance of a macromolecule, but not its disappearance is dependent on molecular size. It is concluded that the disappearance of macromolecules from the peritoneal cavity is mainly a size independent convective process, possibly by lymphatic uptake. This implies that total dextran 70 clearance can be used for measurement of lymphatic absorption in CAPD patients.

Day-to-day variability of protein transport used as a method for analyzing peritoneal permeability in CAPD.

The transperitoneal transport of macromolecules is dependent on both effective peritoneal surface area and intrinsic permeability of the peritoneum. For passage of small solutes, the effective surface area is the main determinant. We hypothesized that day-to-day variations in peritoneal clearances are caused by changes in the effective surface area and not in the intrinsic permeability. Four CAPD (continuous ambulatory peritoneal dialysis) patients without peritonitis were investigated on 28 consecutive days. Concentrations of beta-2-microglobulin, albumin, IgG, and alpha-2-macroglobulin were determined daily in dialysate (night bags) and weekly in serum. Clearances and their coefficients of variation were calculated. Mean coefficients of the intraindividual variation of protein clearances increased, the higher the molecular weight: they ranged from 12% for beta-2-microglobulin clearance to 22% for alpha-2-macroglobulin clearance. Correlations were present between the clearances of albumin, IgG, and alpha-2-macroglobulin, but not between any of these and beta-2-microglobulin clearance. In all patients, protein clearance (C) was a power function of the free diffusion coefficient in water (D) according to the equation: C = a. Db in which b represents the restriction coefficient of the peritoneum, and thus intrinsic permeability. The coefficient of variation of the restriction coefficient was low (range 4-6%). This supports our assumption that the intrinsic permeability is fairly constant on the short term. Day-to-day variations in protein clearances are thus mainly caused by alterations in the effective peritoneal surface area. Long-term follow-up of the restriction coefficient in individual patients might identify those at risk for the development of structural changes in the peritoneal membrane.

The effect of serum albumin at the start of continuous ambulatory peritoneal dialysis treatment on patient survival.

OBJECTIVE: To analyze the effect of serum albumin using immunoturbidimetry, demographic, biochemical, and kinetic factors on survival of continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: A review of prospectively collected data in a 2-year follow-up study of peritoneal transport kinetics. SETTING: University medical center. PARTICIPANTS: Sixty-one patients, evaluated within 3 months after the start of CAPD. MAIN OUTCOME MEASURES: Covariables used in the survival analysis were plasma urea, and creatinine, albumin, hemoglobin, mass transfer area coefficient of creatinine, peritoneal albumin clearance, 4-hour peritoneal albumin loss, net ultrafiltration, age, blood pressure, body mass index, difference between actual and ideal bodyweight, and presence or absence of systemic disease. RESULTS: Overall survival was 64% at 2 years. Median serum albumin was 30.9 g/L, range 18.1-43.9 g/L. Patients with a serum albumin below the median had a lower survival rate than those higher than the median (2-year survival 49% vs 79%, p = 0.01). Using the Cox model, survival was related to systemic disease (p = 0.004), age (p = 0.02), hemoglobin (p = 0.03), and serum albumin (p = 0.1). CONCLUSIONS: The results confirm the strength of serum albumin as predictor of survival. However, in this study serum albumin merely reflected the presence of a systemic disease, which was the most important risk factor for patient survival.

Cancer antigen 125 is locally produced in the peritoneal cavity during continuous ambulatory peritoneal dialysis.

The local production of cancer antigen (CA) 125 in the peritoneal cavity of 14 continuous ambulatory peritoneal dialysis patients was studied. In addition, the relationship between the concentration of mesothelial cells and CA 125 in the peritoneal dialysate effluent was examined. The median results and ranges were as follows: plasma CA 125 14 U/mL (range 10-23), dialysate CA 125 18 U/mL (range 5.2-76), dialysate/plasma ratio 1.9 (range 0.61-5.4), and number of mesothelial cells 400/mL (range 10-5000). Peritoneal concentrations of mesothelial cells and CA 125 were positively correlated (r = 0.50, p < 0.01). Using a monoclonal antibody, CA 125-positive cells were found in the cytospin preparations of the cells of dialysis effluents. All these CA 125 positive cells were also positive for cytokeratin used as a mesothelial cell marker. In vitro experiments using mesothelial cells in monolayers showed a linear increase in CA 125 concentration both in time and in relation to the number of mesothelial cells. From these experiments a production rate of 24 U/hour/10(6) cells could be calculated. It is therefore concluded that CA 125 is locally produced in the peritoneal cavity during CAPD and that the mesothelial cells are the major source of this CA 125.

Evaluation of short-chain polypeptides as an osmotic agent in continuous ambulatory peritoneal dialysis patients.

OBJECTIVES: To assess whether dialysate containing short-chain polypeptides is well tolerated in continuous ambulatory peritoneal dialysis (CAPD) patients and to determine its effect on fluid and solute transport, plasma amino acid levels, and biochemical parameters. DESIGN: Two-treatment, two-period cross-over design. SETTING: Renal Unit, Academic Medical Center, Amsterdam and Renal Unit, University Hospital, Gent. PATIENTS: Two groups of 10 stable CAPD patients. INTERVENTION: All patients received a trial solution (1.36% glucose and 1% peptides, 381 mOsm/kg) and a control solution (2.27% glucose, 404 mOsm/kg) in randomized order. The patients were examined on four consecutive days in which two dwell periods on days 1 and 3 of either 4 (Group I) or 8 hours (Group II) were performed. RESULTS: The peptide solution was well tolerated in all patients. In addition, no differences were found in the parameters for the effective peritoneal surface area and the intrinsic permeability, implying that no irritating effect of the peptide solution was present. Net ultrafiltration was not different in Group I: -43 +/- 125 versus 86 +/- 125 mL (mean +/- SEM) and marginally lower in Group II: -94 +/- 64 versus 51 +/- 64 mL, despite the lower osmolality of the trial solution compared to the control solution. Glucose absorption was higher than the peptide absorption in all patients: Group I: 66 +/- 10% versus 57 +/- 13% (p = 0.0003); Group II: 80 +/- 5% versus 72 +/- 11% (p = 0.006). No differences in plasma amino acid profiles could be detected. CONCLUSIONS: Short-chain polypeptides are absorbed less than glucose and can be used as an osmotic agent in CAPD patients. However, longer-term studies are needed to evaluate possible additional effects of peptides on the nutritional status of CAPD patients.

Dialysate markers of peritoneal tissue during peritonitis and in stable CAPD.

OBJECTIVE: To investigate whether dialysate concentrations of substances that are locally produced within the peritoneal cavity can be used to study the effects of inflammation on peritoneal tissue. DESIGN: We followed the appearance rates (AR) of concentrations of cancer antigen (CA) 125, phospholipids (PHL), hyaluronan (HA), and the procollagen peptides PICP (procollagen 1 C-terminal) and PIIINP (procollagen 3 N-terminal) in dialysate during peritonitis (8 consecutive days) and after recovery. Data were compared with the stable situation. SETTING: CAPD (continuous ambulatory peritoneal dialysis) unit in the Academic Medical Center in Amsterdam. PATIENTS: Twelve CAPD patients with a total of 16 episodes of peritonitis and 10 clinically stable CAPD patients were studied. RESULTS: All substances showed temporal increments in dialysate during peritonitis compared to control. No difference was found between the control day of peritonitis and the stable patients. Maximum AR were reached in the acute phase of peritonitis for CA125, PHL, and HA and on day 4 for both PICP and PIIINP. A second increment in CA125 occurred on days 4 to 6. These findings indicate acute damage to the mesothelium (CA125) and other cells (PHL) by the infection. HA may reflect stromal changes. Subsequently, peritoneal healing (PICP,PIIINP) and remesothelialization (second peak CA125) are likely to occur. CONCLUSIONS: Dialysate concentrations of these substances can be used as markers for the effects of peritonitis on the peritoneum of CAPD patients in vivo. The similarity between the marker concentrations in the effluent after recovery from peritonitis and those in stable CAPD patients implies that complete peritoneal healing is likely to occur after uncomplicated peritonitis.

Indirect measurement of lymphatic absorption with inulin in continuous ambulatory peritoneal dialysis (CAPD) patients.

To elucidate the importance of possible trapping of macromolecules in peritoneal tissue on the calculation of peritoneal lymphatic drainage, we compared the transport of inulin administered i.v. and i.p. in nine continuous ambulatory peritoneal dialysis (CAPD) patients on two separate days. In the intraperitoneal study inulin (5 g) was added to the dialysate and in the intravenous study inulin (5 g) was given i.v. 3 h before the test. No differences were found in the mass transfer area coefficients (MTC) of urea, creatinine, and glucose between the two tests. The MTC after inulin i.p. was 3.2 +/- 0.7 mL/min (mean +/- SD) and after inulin i.v. 1.8 +/- 0.5 (p less than 10(-5]. As the difference in transport kinetics between i.v. and i.p. administration is likely to be caused by lymphatic absorption, a mean lymphatic flow of 1.4 mL/min could be calculated. This value corresponds to the data obtained with macromolecules. Our results therefore favor the hypothesis that no local accumulation of macromolecules in the peritoneal tissues takes place and that their disappearance from the peritoneal cavity represents lymphatic absorption.

Measurement of peritoneal fluid handling in children on continuous ambulatory peritoneal dialysis using autologous hemoglobin.

OBJECTIVE: Previous measurements of peritoneal fluid handling in children treated by continuous ambulatory peritoneal dialysis (CAPD) were performed with human albumin as a fluid marker. A major disadvantage of this substance is that endogenous patient albumin enters the peritoneal cavity during the dwell period. For this reason peritoneal fluid kinetics were measured in a group of children on CAPD, using autologous hemoglobin as a volume marker. DESIGN: Autologous hemoglobin was added to dialysate containing 1.36% glucose as a volume marker. Marker clearance (MC), which is presently the best available approximation of lymphatic absorption in the clinical setting, and transcapillary ultrafiltration (TCUF) were measured during a 4-hour dwell. SETTING: University hospital. PATIENTS: Children on CAPD (N = 9), with a median age of 8.1 years (range 2.1-3.2 years). RESULTS: MC was 521 +/- 166 mL/4 hour/1.73 m2, which is high compared to the literature data on adult CAPD patients. TCUF was 519 +/- 92 mL/4 hour/1.73 m2, which is similar to data concerning adult patients. TCUF reached no maximum during the 4-hour dwell, and the deviation of the TCUF curve from linear was markedly less than usually seen in adult patients. CONCLUSIONS: MC in children treated with CAPD is higher when compared to the literature data on adults. Difficulties to achieve sufficient ultrafiltration in children could be caused by relatively small differences between MC and TCUF from the beginning to the end of the dwell.

The initial decrease in effective peritoneal surface area is not caused by an increase in hematocrit.

The possible relationship between initial changes in functional characteristics of the peritoneal membrane in time and hemoglobin (Hb) or hematocrit (Ht) was analyzed as part of a prospective longitudinal study. The patients were investigated twice: the first time within 3 months after the start of continuous ambulatory peritoneal dialysis (CAPD), and again 4 months later. Mass transfer area coefficients (MTC) for low molecular weight solutes and net fluid removal were calculated during a 4-hour dwell, glucose 1.36%. Thirty-four patients were analyzed. MTC (mean +/- SD, mL/min/1.73 m2), were higher during the first examination: urea 22.6 versus 19.9, p < 0.05; lactate 15.6 versus 13.8, p < 0.001; creatinine 10.5 versus 9.3, p < 0.05; glucose 9.4 versus 7.9, p < 0.001. Net fluid removal was lower during the first examination: 28 versus 99 mL/min/1.73 m2, p < 0.05. Hb and Ht increased between the two examinations (Hb: 5.4 vs 6.1 mmol/L, p < 0.001: Ht: 0.26 vs 0.29, p < 0.001). No relation was found between the absolute or relative change in Hb or Ht and the absolute or relative change in solute and fluid transport between the same examinations. In conclusion, Hb and Ht increased between the first and second examinations. The simultaneously observed changes in peritoneal transport kinetics could not be attributed to changes in Hb or Ht. Therefore, the changes in transport kinetics during the first months on CAPD are probably due to the recent start of the treatment, possibly by an increase in peritoneal surface area. Local irritation by the dialysate may be the causative mechanism.

IgG subclasses in CAPD patients.

OBJECTIVE: To make a comparison of serum levels of immunoglobulin G (IgG) subclasses in adult continuous ambulatory peritoneal dialysis (CAPD) patients with those in age- and sex-matched hemodialysis patients and healthy volunteers, and to analyze the contribution of removal of these proteins in peritoneal effluent to their plasma values. DESIGN: A cross-sectional study. SETTING: A renal unit of a university hospital. PATIENTS: Twenty-three CAPD patients, 21 hemodialysis patients, and 21 healthy volunteers. Peritoneal transport studies were done in 8 of the 23 CAPD patients. METHODS: IgG subclasses were measured in serum by nephelometry. For the peritoneal transport studies an ELISA method on ethylenediamine tetracetic acid plasma was used. The same method was used in seven-to-ten-fold concentrated peritoneal dialysate. RESULTS: CAPD patients had lower IgG2 and IgG4 levels than hemodialysis patients and healthy volunteers (p < 0.01). IgG2 values below 1.5 g/L were present in 43% of the CAPD patients (p < 0.001 compared to healthy volunteers). Peritonitis incidence was not different between CAPD patients with low or normal IgG2 plasma levels. Peritoneal clearance of IgG3 was lower than that of the other subclasses. Evidence was obtained for a depressed synthesis of IgG2 and IgG4 in CAPD patients. The hypothesis that interleukin-2 may be involved in the low synthesis rate of IgG2 is discussed. CONCLUSION: Low serum IgG2 and IgG4 levels are present in stable, adult CAPD patients. These were not caused by increased peritoneal loss, but by decreased synthesis.

Accuracy of erythropoietin determination in the dialysate of CAPD patients.

In vitro experiments were performed to analyze problems with the determination of erythropoietin in dialysate. Human recombinant erythropoietin (EPO; 4000 U/L) was added to several fluids, to glass or polystyrene tubes with or without addition of bovine serum albumin (BSA) and to dialysate bags. The recovery in peritoneal effluent was 4120 +/- 203 U/L (mean +/- SEM). The recovery in the other fluids was less than 50% but in glass tubes it increased to 96% after addition of BSA. Binding was also found to the dialysate bag, therefore reducing the amount available for absorption. We recommend that EPO samples from the dialysate are drawn within BSA coated glass tubes.

Residual volume measurements in CAPD patients with exogenous and endogenous solutes.

Accurate residual volume (RV) measurements are needed in studies on fluid kinetics during CAPD. In this study 10 stable CAPD patients were examined twice within 1 week. On both occasions RV after drainage was calculated by the indicator dilution method. Exogenous (dextran 70, inulin) and endogenous (albumin, IgG, urea, creatinine) solutes were used as markers. RV calculated with endogenous solutes (mean +/- SD) were significantly higher than those calculated with dextran (232 +/- 77 mL) and inulin (223 +/- 73): albumin (389 +/- 123), IgG (497 +/- 180), urea (465 +/- 129) and creatinine (429 +/- 109). The relationship between RV calculated with exogenous solutes was much better than between those calculated with endogenous solutes: dextran vs inulin (r = 0.91), albumin vs IgG (r = 0.69) and urea vs creatinine (r = 0.63). Since mass transport of endogenous solutes during rinsing time exceeds mass transport of dextran and inulin, RV was also calculated after corrections had been made for diffusive mass transport of endogenous solutes during the rinsing procedure. After this correction only albumin was similar to exogenous solutes (244 +/- 111 mL) and had an acceptable confidence interval when compared to dextran. No correlation was found between RV on the first and second day, suggesting large intra-individual variability. We conclude that RV should be calculated with dextran or inulin. When no exogenous solutes are used, albumin is the best alternative. However, only rough estimations are obtained when no correction for diffusion is applied.

Individual characterization of the peritoneal restriction barrier to macromolecules.

The transport of macromolecules such as proteins and dextrans during CAPD is restricted by the permeability of the peritoneum. When its degree is determined by diffusion characteristics of macromolecules, the intrinsic permeability of the peritoneal membrane can be expressed as the relation between clearance of macromolecules and parameters of diffusion velocity. In order to characterize the peritoneal restriction barrier in individual patients, such a relationship has to meet the following conditions: (a) a good fit to linearity, (b) a low inter- and intra individual variability and (c) similarity for proteins and equal sized dextran fractions. In the present study a comparison is made between the reciprocal plot (RP): C-1 = s (esr) + A and the diffusion plot (DP): C = A'. Ds20,w. In these equations C is clearance, esr is Einstein Stokes radius, D20,w is the free diffusion coefficient in water, A and A' are constants, while s is the slope of the regression line and therefore represents intrinsic peritoneal permeability to macromolecules. The 95% confidence interval of the correlation coefficient r was above 0.95 in all studies for the RP and the DP. In general it was somewhat higher for the DP. The inter-individual coefficient of variation was lower in the DP than in the RP. This was also the case for the intra-individual coefficient of variation of the slope for proteins (DP 4% vs RP 27%, p less than 0.01) and for dextrans (DP 18% vs RP 47%, p less than 0.05). The correlation coefficient between dextran slopes and protein slopes was higher for DP (r = 0.68) than for RP (r = 0.50).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of glucose polymers on water removal and protein clearances during CAPD.

Two selected groups of 5 continuous ambulatory peritoneal dialysis (CAPD) patients (3 female, 7 male), mean age 60 years, were studied twice with an interval of 4 weeks. The first study was done with glucose-containing dialysate and the second study with dialysate containing glucose polymers (Dextrin 7.5%) after they had been treated with this solution (night dwell) for 4 weeks. The patients collected night bags for 3 consecutive days during the tests. Protein clearances were determined for beta 2-microglobulin, albumin, IgG, fibronectin, and alpha 2-macroglobulin in both periods to examine the influence of crystalloid-induced convection versus "colloid"-induced convection. Group I normally used 1.50% glucose and was therefore considered to have a "high ultrafiltration";group II was the "low ultrafiltration" group because they needed 4.25% glucose dialysate. For their usual glucose solutions the net ultrafiltration was not different between both groups, but the clearance of beta 2-microglobulin was higher in group II:839 +/- 98 microL/min (group I) and 1135 +/- 131 microL/min (group II) (p = 0.08). For glucose polymers the net ultrafiltration increased in both groups, but this was more pronounced in group II: 657 +/- 104 mL (group I) and 918 +/- 85 mL (group II) (p = 0.06). Also, the clearance of beta 2-microglobulin increased with the glucose polymer solution: 1268 +/- 94 microL/min (for glucose polymer) and 987 +/- 85 microL/min (for glucose) (p < 0.05), but the clearances of the larger serum proteins remained unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of amphotericin B on fluid kinetics and solute transport in CAPD patients.

Loss of net ultrafiltration capacity is an important complication in long-term continuous ambulatory peritoneal dialysis (CAPD). It has been reported in animal studies that the drained volumes after a dwell period were larger when amphotericin B had been given intraperitoneally. In this study the effect of intraperitoneally administered amphotericin B on fluid kinetics was evaluated in 3 CAPD patients. The first patient lost 2.5 kg body weight during the first 4 days of treatment, whereas the net ultrafiltration in the second patient was higher in the treatment period compared with the nontreatment period (750 +/- 38 mL/day vs 438 +/- 34 mL/day (mean +/- SEM), p < 0.0001). In the last patient it can be demonstrated that the increase in the net ultrafiltration was caused by an increase in the transcapillary ultrafiltration (570 vs 454 mL/4 hours), but that lymphatic absorption was not different (251 vs 265 mL/4 hours). The higher transcapillary ultrafiltration capacity is probably caused by an increase in the hydraulic permeability. It is likely that this phenomenon is governed by the interaction of amphotericin B with membrane-bound cholesterol leading to the formation of transcellular pores. However, the administration of amphotericin B caused a chemical peritonitis, probably due to its solvent, sodium desoxycholate. Therefore, before amphotericin B can be used for the treatment of CAPD patients with ultrafiltration failure, further investigations are necessary to obtain a solvent for amphotericin B that is nontoxic and causes no chemical peritonitis.