Search PubMed⌕ Search

Biomedical subjects

G C Koomen

Publications and source records attributed to G C Koomen.

At least 19 recordsLinked to original sources
PubMed1996

Circadian rhythm in glomerular transport of macromolecules through large pores and shunt pathway.

In previous studies we have demonstrated that the circadian rhythm in renal clearance of serum proteins is more pronounced than the variability in glomerular filtration rate, and that the highest day-night fluctuations are found for the largest proteins. To analyze whether additional circadian rhythmicity in size-selective glomerular transport could explain these phenomena, we measured renal clearances of inulin and dextrans in a range of 30 to 90 A over a period of one day and compared these data with renal clearance in proteins. Eight patients with nephrotic syndrome and a GFR > 60 ml/min and 6 healthy volunteers were studied during a protocol of bed rest and spaced protein and fluid intake. After administration of a loading dose, inulin and dextran were continuously infused. Blood and urine were sampled every three hours. In patients, but not in normals, fractional clearances of dextrans larger than 45 A showed a circadian rhythm with a peak in daytime and a close phase-relationship with the rhythm in GFR. The day-night differences were the most pronounced for the largest dextrans. Analysis of the day-night differences in a computer model showed circadian variability in transport through the shunt pathway and through large pores. These results can, to an important degree, explain our previous observations on circadian variability in renal clearance of proteins in patients with nephrotic syndrome.

Adult↗
PubMed1996

Fluid kinetics in CAPD patients during dialysis with a bicarbonate-based hypoosmolar solution.

The magnitude of transcapillary backfiltration by the colloidosmotic pressure within the peritoneal capillaries compared to the effective lymphatic absorption was investigated in continuous ambulatory peritoneal dialysis patients. This was done during a 4-hour dwell period, using a hypoosmolar dialysis fluid (280 mosm/kg H2O) in 8 patients and compared to 5 of these patients using a 1.36% glucose (GS; 324 mosm/kg H2O). The low molecular weight solute transport did not differ between the two solutions. The intraperitoneal dextran 70 concentration increased during the dwell with the hypoosmolar dialysis fluid (from 770 to 945 mg/l; p = 0.000002) and decreased with the GS (from 859 to 719 mg/l; p = 0.007). With the GS the transcapillary ultrafiltration was directed towards the abdominal cavity during the dwell period. With the hypoosmolar fluid, the transcapillary ultrafiltration was continuously directed towards the circulation. In this solution, the magnitude of transcapillary backfiltration due to colloidosmotic pressure within the peritoneal capillaries was 0.4 +/- 0.1 ml/min. In conclusion, intraperitoneal markers can be used in continuous ambulatory peritoneal dialysis patients for determination of effective lymphatic absorption and transcapillary fluid passage in both transport directions.

Adult↗
PubMed1996

Effect of electric charge on the transperitoneal transport of plasma proteins during CAPD.

BACKGROUND: Controversy exists as to whether electric charges of plasma proteins influence their transport across the peritoneal membrane during CAPD. Fixed negative charges in the peritoneal membrane are diminished during peritonitis in rats. METHODS: Peritoneal clearances of 10 proteins and their isoforms were used to establish the relationship between peritoneal clearance and molecular weight. The observed protein clearances were compared with the predicted clearances based on molecular weight. Clearances of proteins with different charge but identical size were compared. Stable patients and peritonitis patients were compared. Results. Only the peritoneal clearance of lipase, LDH 4/5 and IgG3 were significantly different from the predicted values (P<=0.05). The peritoneal clearance of slightly anionic beta2 microglobulin (1072 microl/min) and cationic lysozyme (572 microl/min) showed no evidence for charge selectivity; neither did the peritoneal clearance of slightly anionic transferrin (86 microl/min) and highly anionic albumin (99 microl/min). The peritoneal clearance of IgG1, IgG2 and IgG4 were identical (32, 31 and 31 microl/min), despite their different charge. The peritoneal clearance of cationic LDH 4/5 was 137 microl/min and higher than the peritoneal clearance of neutral LDH 3 (97 microl/min, P=0.01) and LDH 1 (59 microl/min, P=0. 02). These results suggested charge selectivity; however in five additional patients during peritonitis the peritoneal clearance of LDH 4/5 increased to 10 times the peritoneal clearance of LDH 1. Local LDH isoenzyme release from the cells present in the dialysate was shown to be responsible in stable and peritonitis patients. Likewise, the higher peritoneal clearance of neutral pancreatic amylase (234 microl/min) compared to anionic salivary amylase (142 microl/min, P=0.03) could probably be attributed to local release of the former from the pancreas, as the peritoneal clearance of lipase (highly anionic) was higher than predicted and the difference remained during peritonitis. CONCLUSIONS: The peritoneal membrane constitutes a size- but probably not a charge-selective barrier for the transport of macromolecules between blood and dialysate during stable CAPD.

Adult↗
PubMed1995

The standard peritoneal permeability analysis: a tool for the assessment of peritoneal permeability characteristics in CAPD patients.

Peritoneal transport characteristics in CAPD patients are often assessed by the peritoneal equilibration test (PET), which uses a four hour dwell with glucose 2.27% dialysate. From the test, the dialysate/plasma ratio of creatinine (D/PCr), the dialysate/initial dialysate ratio of glucose (D/Do) and net ultrafiltration (NUF, drained minus instilled volume) are calculated. The standard peritoneal permeability analysis (SPA) is a modification and extension of the PET: glucose 1.36% dialysate is used, to which dextran 70 (1 g/liter) is added for the calculation of fluid kinetics. Mass transfer area coefficients (MTAC's) of low molecular weight solutes, clearances of proteins and the change in intraperitoneal volume (delta IPV) can be assessed. In this study the SPA was analyzed, and a comparison with the PET was made. A total number of 138 SPA's was analyzed in 86 different clinically stable patients. Normal values were calculated for both SPA and PET parameters in the same tests. Median (ranges) of comparable transport parameters from SPA and PET were: MTACCr, 10.4 ml/min (5.7 to 19.3); glucose absorption, 61% (35 to 87); delta IPV, 9.5 ml (-761 to 310); D/PCr, 0.76 (0.53 to 1.14); D/D0, 0.37 (0.13 to 0.56); NUF, -75 ml (-675 to 450). The agreement between SPA and PET was analyzed using the method of Bland and Altman. A fairly good agreement was present between NUF and delta IPV. Systematic errors were found when D/PCr and MTACCr were compared: D/P overestimated MTAC mainly in the low range, whereas in the high range values were underestimated. A similar pattern was seen for the transport parameters of glucose. In 40 patients negative net ultrafiltration was present, and possible reasons for this were assessed. In 9 patients no reason could be identified. It can be concluded that the SPA provides useful and extensive information on peritoneal transport parameters. Compared to the PET, the SPA has better discriminative power for the transport of glucose and creatinine.

Adult↗
PubMed1995

Time course of inulin and creatinine clearance in the interval between two haemodialysis treatments.

BACKGROUND: Urinary volume of haemodialysis patients with residual renal function increases during the interdialytic interval. The contribution of GFR to this change in water and solute excretion has not been quantified in detail. The creatinine clearance (Clc) as a determinant of the GFR may overestimate GFR caused by the tubular secretion of creatinine. Cimetidine has been used to inhibit the secretion of creatinine in non-dialysed patients. No data are available on its usefulness in haemodialysis patients. METHODS: Two identical interdialytic intervals (DI) of 3 days (DI-1, DI-2) were investigated in 11 patients. The interval between DI-1 and DI-2 was 1 week. During DI-2 cimetidine 800 mg daily was administered. Each DI was divided in four urine-collection periods. RESULTS: The water and solute excretion in DI-1 and DI-2 were similar. Urinary production increased from 0.37 +/- 0.30 ml/min to 0.66 +/- 0.33 ml/min (P < 0.05), inulin clearance (Cli) increased from 1.8 +/- 1.1 ml/min to 2.7 +/- 1.2 ml/min (P < 0.05), fractional sodium excretion from 9.0 +/- 5.7% to 14.5 +/- 9.0% (P < 0.05). In contrast to Cli the Clc showed no increase during the interdialytic interval both in DI-1 and DI-2. The overestimation of GFR by creatinine (Clc-Cli) decreased during DI-1 from 1.35 +/- 1.69 ml/min to 0.26 +/- 0.60 (P < 0.05) and during DI-2 from 1.01 +/- 1.33 ml/min to 0.10 +/- 0.67 (P < 0.01). The ratio Clc/Cli decreased during DI-1 from 1.78 +/- 0.53 to 1.09 +/- 0.19 (P < 0.01) and during DI-2 from 2.02 +/- 1.13 to 1.05 +/- 0.30 (P < 0.01). All parameters were not different between the comparable days of DI-1 and DI-2. CONCLUSION: We conclude that the urinary volume in the interdialytic interval is directly related to changes in GFR. During the interdialytic interval GFR increased and tubular secretion of creatinine decreased. The administration of cimetidine did not improve the accuracy of Clc as a measurement of GFR in end-stage renal failure.

Adult↗
PubMed1995

Drawbacks of the constant-infusion technique for measurement of renal function.

We investigated the validity of the steady-state constant infusion method (CIM), in which quantitative urinary recovery and constant plasma concentrations of the solute infused are required. Successive 3-h clearances of inulin and p-aminohippuric acid (PAH) were determined for 27 h in 25 patients with renal disease. Results were compared with the standard method of bladder clearance (StM) and with a modified CIM (ModCIM). The 24-h urinary recovery was incomplete for both inulin and PAH. Mean 24-h ModCIM inulin clearance overestimated StM by 4.5 ml.min-1 x 1.73 m-2 (range 0-9, P < 0.001) independent of the extent of renal impairment and pointed to slow distribution and/or extrarenal clearance of inulin. For PAH, the difference between ModCIM and StM clearance was related to the average PAH clearance by ModCIM and StM (r = 0.78). Furthermore, neither plasma inulin nor PAH became completely constant, because of the circadian rhythm in renal function. In conclusion, the conditions of the steady-state CIM technique are not fulfilled, and the method is not suitable for accurate measurement of inulin and PAH clearance, especially when the clearance is low.

Adolescent↗
PubMed1995

Cancer antigen 125: a bulk marker for the mesothelial mass in stable peritoneal dialysis patients.

Mesothelial cells that line the peritoneal cavity are capable of producing several proinflammatory cytokines such as interleukin-6 and interleukin-8. Since they are the most numerous cell in the peritoneal cavity when the lining mesothelial cells are included, they may play a major role in the local antibacterial defence mechanism. Cancer antigen (CA)125 is expressed by mesothelial cells (as by other coelomic epithelium-derived cells) and might therefore be considered a marker of the mesothelium. The aim of this study was to determine whether CA125 is a bulk or an activation stage mesothelial cell marker. A positive correlation was found between the mesothelial cell number and the CA125 concentration in dialysate of stable PD patients (P = 0.03). CA125 release by mesothelial cell cultures during confluence showed that the release per cell was constant in time. Stimulation of mesothelial cells in a confluential phase with IL1 beta, TNF alpha, IFN gamma and TGF beta did not result in an increase in CA125 release. Cell lysis showed that CA125 is also present intracellularly. This implies that release of intracellular CA125 can be a disturbing factor in interpreting the CA125 concentration of dialysate in situations where mesothelial cell death may occur, such as in peritonitis. It can be concluded, that our data show that dialysate CA125 is a bulk marker for the mesothelial cell mass in stable PD patients and can thus provide data on the state of the peritoneal membrane in the follow-up of the individual patient.

Adult↗
PubMed1995

Nitrate in stable CAPD patients and during peritonitis.

During continuous ambulatory peritoneal dialysis (CAPD) peritoneal vessels are dilated. Nitric oxide (NO) causes vasodilation in many organs. Nitrate, a stable metabolite of NO, was measured in plasma and dialysate. In 6 stable CAPD patients standard peritoneal analyses were performed. The mass transfer area coefficient (MTAC) of nitrate was 11.5 mL/min (10.0-17.0 mL/min) (median and range). The MTAC of creatinine was of the same order of magnitude: 10.7 mL/min (8.0-14.2 mL/min), although the molecular weight of nitrate is lower (62 vs 113 dalton). The correlation between the MTAC of nitrate and the MTAC of creatinine indicated diffusion from the circulation and not local production of NO (r = 0.71; p = 0.11). Peritoneal permeability is increased in the acute phase of peritonitis, partly caused by extensive vasodilation. The potential role of NO during peritonitis was investigated in 8 CAPD patients with 11 peritonitis episodes in the acute phase and after recovery. The median dialysate/plasma (D/P) ratio of nitrate in the acute phase was 1.47 (range 0.96-2.55), which was higher than after recovery: 1.07 (0.99-1.75), p < 0.05. No relation was found between the D/P ratio of nitrate and the D/P ratio of TNF alpha (tumor necrosis factor). In conclusion, dialysate nitrate levels in stable CAPD patients are likely to be determined by diffusion from the circulation. D/P ratios exceeding 1.0 during the acute phase of peritonitis are probably the result of local NO production. This may contribute to the marked vasodilation during peritonitis.

Acute Disease↗
PubMed1995

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.

Adult↗
PubMed1994

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.

Adult↗
PubMed1994

Radiation reduces cyclooxygenase activity in cultured human endothelial cells at low doses.

The effect of radiation on prostaglandin (PG) production was investigated in cultured human umbilical vein endothelial cells. It was found that 48 hours after irradiation the endothelial cell capacity to synthesize prostacyclin (PGI2), Prostaglandin E2 (PGE2) and prostaglandin F2 alpha (PGF2 alpha) from exogenous arachidonic acid (AA) was strongly reduced in a radiation dose-dependent way, with 50% of the maximal inhibition at approximately 2 Gy. By incubating the endothelial cells between 24 and 48 hours after irradiation with 50 U/ml interleukin-2 (IL-2), which is known to selectively stimulate de novo synthesis of cyclooxygenase, the PGI2 synthesis from exogenous AA was nearly completely restored. Basal PGI2 release was not influenced by radiation (up to 25 Gy), nor was there increased cell damage as measured by LDH release during 72 hours after irradiation compared with controls. Clonogenic cell survival after irradiation showed a typical exponential radiation dose-response curve with a fairly broad initial shoulder. The data presented in this study suggest that the reduction of endothelial PGI2 synthesis after low doses of radiation is primarily due to a reduction in the activity of the enzyme cyclooxygenase.

Arachidonic Acid↗
PubMed1994

A prospective study of peritoneal transport in CAPD patients.

A prospective two year follow-up study of the functional characteristics of the peritoneal membrane was conducted in 61 CAPD patients. Peritoneal transport of solutes, calculated by mass transfer area coefficients for urea and creatinine, peritoneal clearances for proteins, percentage of absorption of glucose, as well as net ultrafiltration were measured every four months. After five months on CAPD a decrease was found for the transport of most solutes (P < 0.05, mean values, ml/min/1.73 m2): urea 18.1 to 16.2, creatinine 9.5 to 8.4, IgG 0.049 to 0.040 and alpha 2-macroglobulin 0.020 to 0.015, as well as for the absorption of glucose (57.9 to 53.2%, P < 0.05). Net ultrafiltration increased simultaneously from 44.6 to 100.5 ml/4 hr/1.73 m2, P < 0.05. From five months to two years on CAPD a significant increase in the transport of all solutes except alpha 2-macroglobulin was found, as well as a decrease in net ultrafiltration. Peritoneal transport at the end of the study was not significantly different from the starting values. Our findings indicate an initial effect of CAPD itself on peritoneal transport, probably due to the recent start of the treatment. Baseline values were reached after five months on CAPD. Thereafter a gradual increase in peritoneal solute transport occurred during two years of treatment. This can be explained by an increase in the effective peritoneal surface area.

Adult↗
PubMed1994

Fluid and solute transport in CAPD patients using ultralow sodium dialysate.

Transcapillary ultrafiltration during CAPD is determined by the ultrafiltration coefficient of the peritoneal membrane and by Starling forces, the latter being mainly determined by the osmolality of the dialysate. Dialysate sodium concentration decreases during a dwell, implying that: (1) sodium passes the peritoneal membrane to a lesser extent than H2O, and (2) more H2O than sodium is removed in overhydrated patients. We therefore compared two dialysate solutions with similar osmolality, but different sodium concentration (Na+ 129 mmol/liter and 102 mmol/liter). Two peritoneal permeability tests (2 x 6 hrs, dextran 70 as volume marker) with an interval of two days were performed in 10 CAPD patients. Transcapillary ultrafiltration rate was higher with ultralow sodium dialysate (USD) than normal sodium dialysate (NSD): 1.80 +/- 0.16 ml/min versus 1.58 +/- 0.18 (P < 0.01). It was especially higher during the last two hours of the dwell: 0.49 +/- 0.12 ml/min (USD) versus 0.27 +/- 0.13 (NSD). The effective lymphatic absorption rate was not different: 1.01 +/- 0.12 ml/min (USD) versus 1.05 +/- 0.09 (NSD). Using two different kinetic models, the reflection coefficients for glucose, sodium and chloride were 0.032, 0.029 and 0.027 (for the convection model) and 0.033, 0.030 and 0.027 (for the diffusion model). As a consequence the decline in osmotic pressure was more gradual during the exchange with USD. The peritoneal membrane characteristics, that is the effective peritoneal surface area and the peritoneal restriction coefficient, were not altered by the composition of the dialysate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Clinical significance and detection of individual differences and changes in transperitoneal transport.

A review is given on the pathophysiology of the transport of solutes and fluid during continuous ambulatory peritoneal dialysis. Special attention is paid to the assessment of peritoneal permeability in individual patients, its inter- and intraindividual variability, the effect of systemic disease, some regulatory mechanisms, and alterations observed during long-term continuous ambulatory peritoneal dialysis.

Adult↗
PubMed1994

Circadian rhythm of glomerular filtration rate in patients after kidney transplantation.

Within 6 months of a kidney transplantation the graft can be regarded as an organ deprived of its innervation. We analysed whether the transplanted kidney has a diurnal rhythm of its glomerular filtration rate (GFR) similar to the GFR rhythm that has been demonstrated in normal individuals and in patients with nephrotic syndrome. GFR was measured by inulin clearances every 3 h during 1 day of bed-rest and identical food and fluid intake per 3 h in seven patients, 4-7 months after a successful kidney transplantation, and in 10 healthy volunteers. Similar to these healthy subjects, a normal circadian rhythm of GFR was detected in all but one patient with a maximum of 57 (range 45-82) ml/min in daytime, a minimum of 47 (range 36-70) ml/min during the night and a relative amplitude of 21 (range 10-41)%. The circadian rhythm of GFR was absent in the patient with the lowest value of GFR (39 ml/min). In conclusion, GFR has a circadian rhythm in patients studied within 6 months of a kidney transplantation, despite the absence of renal innervation.

Adult↗
PubMed1994

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.

Adult↗