Indices of peritoneal permeability and surface area.
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Biological Transport↗
Biomedical subjects
G C Koomen
Publications and source records attributed to G C Koomen.
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.
Adult↗
Ultrafiltration failure in continuous ambulatory peritoneal dialysis.
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Biological Transport↗
Creatinine clearance during cimetidine administration for measurement of glomerular filtration rate.
Creatinine clearance inaccurately estimates true glomerular filtration rate (GFR) because of tubular secretion of creatinine. We studied the ability of oral cimetidine, a blocker of tubular creatinine secretion, to improve the accuracy of measuring creatinine clearance. Clearances of inulin and endogenous creatinine were simultaneously measured in 16 patients with renal disease before administration of cimetidine and during 8 successive 3 h clearance periods with cimetidine 400 mg as priming dose followed by 200 mg every 3 h. At baseline, creatinine relative to inulin clearance (ClC/Cll) ranged from 1.14 to 2.27. With cimetidine, ClC/Cll approached unity in 8 patients (mean 1.02 [SD 0.03]), but considerably exceeded unity in 8 others (1.33 [0.14]). Plasma cimetidine/creatinine ratio was smaller in this second group, due to significantly higher renal clearance of cimetidine (333 [136] vs 165 [89] ml/min, p = 0.01). In a further study, cimetidine dose and, consequently plasma cimetidine concentration, was increased in 6 additional patients who had incomplete inhibited previously. This increased dose completely inhibited tubular creatinine secretion in the third until the sixth hour, so that creatinine clearance equalled GFR. Provided an adequate dose of cimetidine is given, 24 h creatinine clearance during administration of drug measures GFR accurately in patients with renal disease. However, because of the maximum daily dose of cimetidine that is advised, short clearance times (3 h) are recommended.
Adolescent↗
Indirect measurement of lymphatic absorption in CAPD patients is not influenced by trapping.
The disappearance rate of intraperitoneally administered macromolecules is often used to calculate lymphatic absorption during CAPD. The possible contribution of local accumulation (trapping) of such solutes in the tissues surrounding the peritoneal cavity, leading to overestimation of lymphatic flow, was investigated in eight CAPD patients. They were studied twice during a four hour dwell, glucose 1.36%, to which polydisperse neutral dextran 70 1 g/liter had been added for measurement of lymphatic flow. After the test on day 1 dextran 130 mg/kg was given intravenously and also dextran 1 g/liter was added to every following dialysis bag until the second test on day 3. This was done to saturate the tissues surrounding the peritoneal cavity and thereby to create a steady state condition. In one patient the dextran administration was continued until a third study was done on day 5. Dextran in serum during day 3 was 1.3 +/- 0.5 g/liter (mean +/- SD). No difference in peritoneal clearance of dextran was found between day 1 and day 3 (1.11 +/- 0.56 versus 0.97 +/- 0.41 ml/min). Also no difference was found between day 1 (0.32), day 3 (0.62), and day 5 (0.42 ml/min). Trapping would have influenced the first but not the second test, as the second time all tissues were saturated with dextran. As the dextran absorption rate remained the same, this indicates that trapping is of no importance and that lymphatic absorption can be measured by the disappearance of a macromolecular marker.
Absorption↗
Effects of tracer, volume, osmolarity and infection on fluid kinetics during CAPD.
A review is given on various aspects of using the disappearance rate of intraperitoneally administered macromolecules for the determination of fluid kinetics in CAPD patients. The rationale and mathematics for the calculation of transcapillary ultrafiltration and of indirect measurement of lymphatic absorption are described. A comparison is made between autologous haemoglobin, human albumin and dextran 70. Dextran 70 appeared most useful; one brand of human albumin increased solute transport. Lymphatic absorption was higher after the installation of a 3-litre dialysate volume than after a 2-litre one, and also higher during peritonitis than after recovery from infection. A gradual increase in intraperitoneal volume, as obtained with glucose 3.86% dialysate, had no apparent effect on the disappearance rate of dextran 70. It is concluded that intraperitoneally administered dextran 70 is a clinically useful marker for the description of fluid kinetics in CAPD patients under various conditions.
Ascitic Fluid↗
Use of the disappearance rate for the estimation of lymphatic absorption during CAPD.
Several studies are discussed which investigated the usefulness of the disappearance rate of macromolecules from the peritoneal cavity for estimating convective fluid loss from the peritoneal cavity into the peritoneal lymphatic system. It is shown that dextrans are removed from the peritoneal cavity by a size-independent process at a mean rate of 1.37 +/- 0.15 ml/min, whereas the clearance from blood to dialysate of dextrans is size-dependent. The fluid removal rate estimated by the difference in bidirectional transport of inulin (1.79 +/- 0.38 ml/min; p < 0.0005) was of the same order of magnitude as has been found using the removal rate of macromolecules from the peritoneal cavity. Also, the role of local accumulation of macromolecules was studied during continuous administration of dextrans. No differences were found in the dextran disappearance rate before and after saturation of the peritoneal interstitium with dextran (1.1 +/- 0.6 vs. 1.0 +/- 0.4 ml/min). During a study using a hypoosmotic solution we calculated a net transcapillary backfiltration of fluid, whereas the dextran removal rate was in the same order of magnitude as found using commercially available dialysate. In our opinion, the disappearance rate of macromolecules is an estimate of convective fluid loss from the peritoneal cavity into the peritoneal lymphatic system.
Absorption↗
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.
Adult↗
Discrepancy between circadian rhythms of inulin and creatinine clearance.
To elucidate the disparity between circadian rhythmicity of inulin and creatinine clearance, we simultaneously measured inulin and creatinine clearances every 3 hours during 1 day in 14 normal subjects and in 8 patients with nephrotic syndrome. All patients and normal subjects had a circadian rhythm for inulin clearance with a maximum during daytime and a relative amplitude of 21% +/- 2%. For creatinine clearance a rhythm was either absent or reduced in relative amplitude (p less than 0.01). In all subjects the rate of tubular creatinine secretion was higher at minimum of inulin clearance (night) than at maximum (day). The fractional clearance (relative to inulin) of creatinine was also higher during the night: normal subjects, 1.28 +/- 0.02 versus 1.10 +/- 0.02; patients, 1.78 +/- 0.08 versus 1.45 +/- 0.05 (p less than 0.005). This demonstrates the inaccuracy of creatinine clearance as a measure of glomerular filtration rate (GFR). By subsequent blocking of the tubular secretion of creatinine with cimetidine in four normal subjects, creatinine clearance became similar to inulin clearance during day and night. This confirms that high tubular secretion of creatinine during the night counteracts the normal rhythmicity of glomerular filtration of creatinine. As a result, plasma creatinine concentration is nearly constant during a 24-hour period. In conclusion, tubular creatinine secretion has a circadian rhythm with a phase opposite to the rhythm of GFR, thus blunting or causing absence of a circadian rhythm for creatinine clearance.
Adult↗
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)
Humans↗
Effect of intraperitoneal administration of two different batches of albumin solutions on peritoneal solute transport in CAPD patients.
The effects of intraperitoneal administration of two different batches of human albumin (batch A and batch B) on peritoneal solute transport and dialysate white cell count were studied in 16 CAPD patients. The studies were done on two separate days during a 4-h dwell, one day without and one day with the intraperitoneal administration of 10 g/l human albumin. Marked differences were found between the two batches. The transport of all measured solutes increased during administration of batch A compared to the control experiments: urea 78% +/- 62%, lactate 51% +/- 38%, creatinine 96% +/- 54%, glucose 67% +/- 55%, inulin 27% +/- 33% IgG 126% +/- 80%, mean +/- SD; P less than 0.02). In the experiments with batch A the white cell count of the test bag was greater than that of the effluent ('night bag') before the test (13 +/- 5 vs 194 +/- 61 mm3/l; P less than 0.02). These effects were also observed when the dialysate was buffered to pH = 7.4 before inflow. Albumin batch B showed no effect on solute transport and white cell count. The effects of solute transport and white cell count are probably caused by the greater concentration of prekallikrein activator in batch A when compared to batch B (30.1 vs 0 U/l). Caution is warranted when human albumin is used for simultaneous measurement of peritoneal fluid and solute kinetics.
Absorption↗
Effects of renal failure on complement C3d levels.
Elevated plasma concentrations of complement split product C3d have been reported to represent activation of the complement system. In the present study the effect of renal function on C3d concentrations was investigated in patients with various degrees of renal impairment, in patients with chronic renal failure and in CAPD patients. It appeared that elevated plasma C3d concentrations were present in patients with plasma creatinine concentrations in excess of 200 mumol/l regardless of the type of kidney disease. It is very likely that this can be attributed to renal handling (i.e. glomerular filtration, tubular reabsorption and renal catabolism) of C3d in a similar way as has been demonstrated for other low molecular weight proteins. The peritoneal permeability to C3d was slightly less than could be expected on the basis of its molecular weight without evidence of local production of C3d. Renal function should be taken into account in the interpretation of elevated plasma concentrations of C3d.
Complement Activation↗
Functional characteristics of the peritoneal membrane in long-term continuous ambulatory peritoneal dialysis.
Peritoneal transport characteristics of 20 long-term (LT) patients with a mean duration on continuous ambulatory peritoneal dialysis (CAPD) of 60 months were compared with those of 20 matched patients who recently started (RS) CAPD (mean 39 days, range 11-63). Mass transfer area coefficients (MTC) of creatinine, glucose and inulin were higher in the LT group than in the RS group (12.1 versus 9.2 ml/min, p less than 0.01; 9.9 versus 8.3 ml/min, p less than 0.05; 4.1 versus 3.5 ml/min, p less than 0.05). The MTC of alpha 2-macroglobulin were lower in the LT group (13 versus 25 microliters/min; p less than 0.01). The size selectivity of the membrane for the transport of macromolecules, determined as protein MTC ratios, showed a more restricted passage for macromolecules in the LT group. Net fluid removal using glucose 3.86% was lower in the LT patients (487 versus 826 ml/4 h; p less than 0.001). The results indicate the development of a larger effective peritoneal surface area combined with a less permeable peritoneal membrane after many years of CAPD.
Adult↗
Peritoneal transport of macromolecules in patients on CAPD.
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Biological Transport↗
A fast reliable method for the measurement of intraperitoneal dextran 70, used to calculate lymphatic absorption.
The use of intraperitoneally administered dextran 70 was investigated for measurement of lymphatic absorption in CAPD patients. For this purpose a fast, highly accurate HPLC method was developed, that was not influenced by the high glucose concentration in peritoneal dialysate, nor by the inulin that was added to the dialysate for the measurement of residual volume. Pretreatment of the samples consisted of deproteinization with trichloroacetic acid, followed by incubation at 45 degrees C to hydrolyze inulin. This was followed by a further rinsing step using a Sephadex G-25 PD-10 column. The HPLC was performed on a Bio-Gel XL guard column with refractive index detection. Because of the short guard column the chromatographic analysis was only 5 minutes for one sample. With the method described lymphatic absorption rate was measured in 30 CAPD patients and was found to range from 0.1 to 3.5 mL/min, median 1.0 mL/min.
Absorption↗
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)
Biological Transport↗
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.
Adult↗
Transport kinetics of pseudouridine during hemodialysis and continuous ambulatory peritoneal dialysis.
It has been found that the concentrations of pseudouridine in serum of patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are higher than those in patients undergoing hemodialysis. We analyzed whether this could be caused by a lower rate of transport in CAPD when compared with hemodialysis. Mass transfer area coefficients (MTCs) for urea, creatinine, uric acid, and pseudouridine were determined in nine patients undergoing hemodialysis as dialyzer clearances and in 14 patients undergoing CAPD during a 4-hour dwell with 2 L dialysate with glucose, 70 mmol/L. The theoretical MTC of pseudouridine (TPSI), calculated by extrapolation to its molecular weight by use of the MTC of urea, creatinine, and uric acid, was higher than the observed MTC of pseudouridine, both in hemodialysis (136 vs 112 ml/min, p less than 0.025) and in CAPD (6.9 vs 3.4 ml/min, p less than 0.001). The pseudouridine/TPSI MTC ratio was lower during CAPD than during hemodialysis (0.47 vs 0.83, p less than 0.0005), indicating a lower level of transport during CAPD. In vitro experiments with nuclear magnetic resonance spectroscopy supported the hypothesis of glucose-induced molecular association of pseudouridine. Therefore, dialysate containing 10 mmol/L glucose was compared with that containing 70 mmol/L glucose in eight patients undergoing CAPD. The MTC of pseudouridine was higher during the experiments with dialysate containing 10 mmol/L glucose (3.5 +/- 2.0 ml/min vs 2.7 +/- 1.9 ml/min, p less than 0.05). This was also found for the pseudouridine/TPSI MTC ratio (0.61 vs 0.41, p less than 0.02) and the pseudouridine/creatinine MTC ratio (0.33 vs 0.25, p less than 0.02), favoring glucose-induced decrease of MTC-pseudouridine.(ABSTRACT TRUNCATED AT 250 WORDS)
Biological Transport↗