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G C Koomen

Publications and source records attributed to G C Koomen.

69 records · Page 4Linked to original sources

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.

Acetaminophen↗

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.

Adult↗

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.

Dialysis Solutions↗

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.

Biological Transport↗

The time course of peritoneal transport kinetics in continuous ambulatory peritoneal dialysis patients who develop sclerosing peritonitis.

The time course of measurements of peritoneal solute transport in four continuous ambulatory peritoneal dialysis (CAPD) patients who developed sclerosing peritonitis is described. Loss of fluid removal capacity was found in all of them. In three, this loss was associated with an increase in peritoneal absorption of glucose from the dialysate and an increase in the transperitoneal transport rates of low-molecular-weight solutes and proteins. In the other patient a decrease in all these parameters was found. This seems to imply that the effective peritoneal surface area was increased in three patients and decreased in one. Peritoneal permeability to macromolecules remained unchanged as judged by the ratio between the clearance of IgG and albumin. Among the possible factors that contribute to the development of sclerosing peritonitis, some are likely to lead to a larger effective peritoneal surface area, like prostacyclin and the formation of new capillaries in poorly vascularized parts of the peritoneum. Others, such as extensive formation of collagen, could lead to a smaller effective surface area. Individual differences in susceptibility to these factors may lead to an increase or decrease in peritoneal solute transport rates. Follow-up measurements of peritoneal solute kinetics are necessary to identify those patients who are at risk.

Adult↗

The peritoneal transport of serum proteins and neutral dextran in CAPD patients.

The peritoneal transport of five serum proteins and intravenously-administered neutral dextran was studied in 13 CAPD patients. In all patients a study was done three hours after the administration of dextran. In nine the study was repeated after 14 hours, and in six also after 38 hours. Using gel permeation chromatography of serum and dialysate it was possible to calculate fractional (relative to inulin) clearances for dextran fractions with Einstein-Stokes radii ranging from 30 to 90 A. In contrast to glomerular transport, we found that peritoneal clearances of serum proteins and corresponding dextran fractions were of a similar magnitude up to a radius of 90 A, especially in the follow-up studies. No evidence was found for a charge-selective barrier function of the peritoneum. It appeared likely that the peritoneal interstitium is probably a third compartment between blood and dialysate in which equilibrium with blood and dialysate is present for serum proteins, but initially not for dextran. For dextran this equilibrium is probably approached 14 to 38 hours after administration. The linear relationship between the reciprocal of fractional clearances and Einstein-Stokes radii indicates that restricted diffusion is the main transport mechanism of macromolecules across the peritoneal membrane. The slopes of the linear regression between the reciprocal of fractional clearances and radii ranged from 0.32 to 6.95 (slope for free diffusion 0.07) and provided an index of the permeability characteristics of the peritoneal membrane.

Adult↗

Circadian rhythm of glomerular filtration rate in normal individuals.

1. In a group of 11 normal individuals we measured glomerular filtration rate (GFR) by inulin clearances and effective renal plasma flow (ERPF) by p-aminohippurate clearances during a period of 24 h and a regimen of bedrest, identical food intake per 3 h and normal sleep/wake and light/dark cycles. 2. All subjects had a circadian rhythm for GFR with a maximum of 122 ml/min (SD 22) in the daytime, a minimum of 86 ml/min (SD 12) at night and with a relative amplitude of 33% (SD 15). 3. ERPF had a circadian rhythm with a similar relative amplitude as the GFR rhythm, but with a different phase. Because of this difference in phase, the calculated filtration fraction (GFR/ERPF) followed a circadian rhythm as well. 4. The circadian rhythms of urine volume and sodium excretion were in phase with the GFR rhythm, but the potassium rhythm had a different phase, probably because urinary potassium is largely derived from tubular secretion. 5. Urinary albumin and beta 2-microglobulin excretion had a circadian rhythm in phase with the GFR rhythm. 6. The highest quantity of sodium, water and beta 2-microglobulin was reabsorbed in the daytime; tubular reabsorption, expressed as percentage of the filtered load (fractional reabsorption), had a rhythm with a reversed phase.

Adult↗

Circadian rhythm of proteinuria: consequences of the use of urinary protein:creatinine ratios.

Proteinuria in patients with glomerular disease has a circadian rhythm, but for creatinine such a rhythm is either absent or of low amplitude. We found in 18 of 23 admitted patients (group I) and in seven outpatients (group II) a marked circadian rhythm of the protein: creatinine ratio. Estimates of 24-h proteinuria were obtained by multiplying the protein:creatinine ratio of 3-h urine samples with 24-h creatinine excretion, calculated from age, sex and bodyweight. Estimated proteinuria could be as low as 19% or as high as 349% of actually measured 24-h proteinuria; the mean SD was 23%. The best estimate was obtained with the 06.00-09.00 hours urine samples. The estimates correlated better with actually measured 24-h proteinuria than the protein: creatinine ratio per se correlated with the 24-h proteinuria. Day-to-day variation of proteinuria estimates from samples taken at the same time of the day was of similar magnitude as day-to-day variation of actual 24-h proteinuria. We conclude that the usefulness of the protein: creatinine ratio of a random urine sample for estimation of proteinuria is limited, because of the circadian rhythm of proteinuria. However, samples collected at a fixed time of the day are an acceptable alternative for 24-h urine collections in the clinical follow-up of individual patients.

Adolescent↗

Peritoneal fluid kinetics during CAPD measured with intraperitoneal dextran 70.

Simultaneous measurement of transcapillary ultrafiltration (TCUF), lymphatic absorption rate (LAR), and intraperitoneal volume (IPV) was performed by means of intraperitoneally-administered polydisperse dextran 70 in nine CAPD patients during a 4 hr dialysis dwell (glucose 1.36%). The recovery of dextran was 88 +/- 1%. LAR, calculated as the amount of dextran lost, divided by the dialysate dextran concentration, was 1.30 +/- 0.12 ml/min. The time course of TCUF could be described as a hyperbola. Therefore, the application of the Lineweaver-Burke plot made it possible to calculate TCUFmax (median 641 mL) and its half-time (t50: median 211 min). delta IPV4h, calculated as the difference between the Lineweaver-Burke adjusted TCUF4h and LA4h, was correlated with measured delta IPV4h after drainage (r = 0.89, p less than 0.001). The latter was dependent upon LAR (r = -0.71) and effective peritoneal surface area, as represented by mass transfer area coefficients (MTC) of low molecular weight solutes (creatinine r = -0.76, glucose r = -0.81). High MTC values of these solutes were exponentially related to a short t50 (creatinine r = -0.76). LAR was correlated with the MTC of intraperitoneally administered inulin (r = 0.83). Dextran 70 had no measurable effect on solute transport. It is concluded that dextran 70 is a useful marker for the measurement of peritoneal fluid kinetics, even during CAPD with a low glucose concentration in the dialysate.

Adult↗

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.

Acute Disease↗

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.

Adult↗