Relative blood volume changes during haemodialysis estimated from haemoconcentration markers.

Relative blood volume (RBV) monitoring is frequently used in haemodialysis patients to help guide fluid management and improve cardiovascular stability. RBV changes are typically estimated based on online measurements of certain haemoconcentration markers, such as haematocrit (HCT), haemoglobin (HGB) or total blood protein concentration (TBP). The beginning of a haemodialysis procedure, i.e. filling the extracorporeal circuit with the patient's blood (with the priming saline being infused to the patient or discarded) may be associated with relatively dynamic changes in the circulation, and hence the observed RBV changes may depend on the exact moment of starting the measurements. The aim of this study was to use a mathematical model to assess this issue quantitatively. The model-based simulations indicate that when the priming saline is not discarded but infused to the patient, a few-minute difference in the moment of starting RBV tracking through measurements of HCT, HGB or TBP may substantially affect the RBV changes observed throughout the dialysis session, especially with large priming volumes. A possible overestimation of the actual RBV changes is the highest when the measurements are started within a couple of minutes after the infusion of priming saline is completed.

Phenotypic features of vascular calcification in chronic kidney disease.

BACKGROUND: Patients with chronic kidney disease stage 5 (CKD5) are predisposed to vascular calcification (VC), but the combined effect of factors associated with VC was sparsely investigated. We applied the relaxed linear separability (RLS) feature selection model to identify features that concomitantly associate with VC in CKD5 patients. METHODS: Epigastric arteries collected during surgery from living donor kidney transplant recipients were examined to score the histological extent of medial VC. Sixty-two phenotypic features in 152 patients were entered into RLS model to differentiate between no-minimal VC (n = 93; score 0-1) and moderate-extensive VC (n = 59; score 2-3). The subset of features associated with VC was selected on the basis of cross-validation procedure. The strength of association of the selected features with VC was expressed by the absolute value of 'RLS factor'. RESULTS: Among 62 features, a subset of 17 features provided optimal prediction of VC with 89% of patients correctly classified into their groups. The 17 features included traditional risk factors (diabetes, age, cholesterol, BMI and male sex) and markers of bone metabolism, endothelial function, metabolites, serum antibodies and mitochondrial-derived peptide. Positive RLS factors range from 1.26 to 4.05 indicating features associated with increased risk of VC, and negative RLS factors range from -0.95 to -1.83 indicating features associated with reduced risk of VC. CONCLUSION: The RLS model identified 17 features including novel biomarkers and traditional risk factors that together concomitantly associated with medial VC. These results may inform further investigations of factors promoting VC in CKD5 patients.

Comparison of three PET methods to assess peritoneal membrane transport.

The peritoneal equilibration test (PET) is the most widespread method for assessing water and solute transport across the peritoneal membrane. This study compared three methods: traditional PET (t-PET), mini-PET, and modified PET (mod-PET). Non-diabetic adults (n=21) who had been on peritoneal dialysis (PD) for at least three months underwent t-PET (glucose 2.5%-4 h), mini-PET (glucose 3.86%-1 h), and mod-PET (glucose 3.86%-4 h) to determine dialysate-to-plasma concentration ratio (D/P) for creatinine and dialysate-to-baseline dialysate concentration ratio (D/D0) for glucose. Agreement between methods regarding D/P creatinine and D/D0 glucose was assessed using analysis of variance (ANOVA), Pearson's correlation coefficient, and Bland-Altman analysis. D/P creatinine differed between t-PET and mini-PET (P<0.001) and between mod-PET and mini-PET (P<0.01) but not between t-PET and mod-PET (P=0.746). The correlation of D/P creatinine with t-PET vs mod-PET was significant (r=0.387, P=0.009) but not that of t-PET vs mini-PET (r=0.088, P=0.241). Estimated bias was -0.029 (P=0.201) between t-PET and mod-PET, and 0.206 (P<0.001) between t-PET and mini-PET. D/D0 glucose differed between t-PET and mod-PET (P=0.003) and between mod-PET and mini-PET (P=0.002) but not between t-PET and mini-PET (P=0.885). The correlations of D/D0 glucose in t-PET vs mod-PET (r=-0.017, P=0.421) or t-PET vs mini-PET (r=0.152, P=0.609) were not significant. Estimated bias was 0.122 (P=0.026) between t-PET and mod-PET, and 0.122 (P=0.026) between t-PET and mini-PET. The significant correlation of D/P creatinine between t-PET and mod-PET suggested that the latter is a good alternative to t-PET. There was no such correlation between t-PET and mini-PET.

Comparison of three PET methods to assess peritoneal membrane transport

The peritoneal equilibration test (PET) is the most widespread method for assessing water and solute transport across the peritoneal membrane. This study compared three methods: traditional PET (t-PET), mini-PET, and modified PET (mod-PET). Non-diabetic adults (n=21) who had been on peritoneal dialysis (PD) for at least three months underwent t-PET (glucose 2.5%-4 h), mini-PET (glucose 3.86%-1 h), and mod-PET (glucose 3.86%-4 h) to determine dialysate-to-plasma concentration ratio (D/P) for creatinine and dialysate-to-baseline dialysate concentration ratio (D/D0) for glucose. Agreement between methods regarding D/P creatinine and D/D0 glucose was assessed using analysis of variance (ANOVA), Pearson's correlation coefficient, and Bland-Altman analysis. D/P creatinine differed between t-PET and mini-PET (P<0.001) and between mod-PET and mini-PET (P<0.01) but not between t-PET and mod-PET (P=0.746). The correlation of D/P creatinine with t-PET vs mod-PET was significant (r=0.387, P=0.009) but not that of t-PET vs mini-PET (r=0.088, P=0.241). Estimated bias was −0.029 (P=0.201) between t-PET and mod-PET, and 0.206 (P<0.001) between t-PET and mini-PET. D/D0 glucose differed between t-PET and mod-PET (P=0.003) and between mod-PET and mini-PET (P=0.002) but not between t-PET and mini-PET (P=0.885). The correlations of D/D0 glucose in t-PET vs mod-PET (r=−0.017, P=0.421) or t-PET vs mini-PET (r=0.152, P=0.609) were not significant. Estimated bias was 0.122 (P=0.026) between t-PET and mod-PET, and 0.122 (P=0.026) between t-PET and mini-PET. The significant correlation of D/P creatinine between t-PET and mod-PET suggested that the latter is a good alternative to t-PET. There was no such correlation between t-PET and mini-PET.

The Valsalva manoeuvre: physiology and clinical examples.

The Valsalva manoeuvre (VM), a forced expiratory effort against a closed airway, has a wide range of applications in several medical disciplines, including diagnosing heart problems or autonomic nervous system deficiencies. The changes of the intrathoracic and intra-abdominal pressure associated with the manoeuvre result in a complex cardiovascular response with a concomitant action of several regulatory mechanisms. As the main aim of the reflex mechanisms is to control the arterial blood pressure (BP), their action is based primarily on signals from baroreceptors, although they also reflect the activity of pulmonary stretch receptors and, to a lower degree, chemoreceptors, with different mechanisms acting either in synergism or in antagonism depending on the phase of the manoeuvre. A variety of abnormal responses to the VM can be seen in patients with different conditions. Based on the arterial BP and heart rate changes during and after the manoeuvre several dysfunctions can be hence diagnosed or confirmed. The nature of the cardiovascular response to the manoeuvre depends, however, not only on the shape of the cardiovascular system and the autonomic function of the given patient, but also on a number of technical factors related to the execution of the manoeuvre including the duration and level of strain, the body position or breathing pattern. This review of the literature provides a comprehensive analysis of the physiology and pathophysiology of the VM and an overview of its applications. A number of clinical examples of normal and abnormal haemodynamic response to the manoeuvre have been also provided.

Comparison of kinetic characteristics of amino acid-based and dipeptide-based peritoneal dialysis solutions.

UNLABELLED: A mixture of dipeptides (DP) has been proposed as alternatives (to glucose and amino acids, (AA)) osmotic agent in peritoneal dialysis (PD) solutions. DP based solutions may have metabolic and nutritional advantages compared to AA based solutions, as some sources of AA (such as tyrosine) are poorly soluble in water. In a previous study, we compared the kinetic characteristics of DP and AA based solutions; however, the amount of AA differed substantially. The aim of the present study was to compare solutions with almost equal amounts of AA. METHODS: The following solutions were used: (1) amino acid (AA) solution containing leucine, valine, lysine, isoleucine, threonine, phenylalanine and histidine (tyrosine was omitted because of its poor solubility), (2) dipeptide (DP) solution containing leucyl-valine, lysyl-isoleucine, threonyl-phenylalanine and histidyl-tyrosine. Sixteen Sprague-Dawley rats were divided in two groups and were subjected to intraperitoneal injection of either 25 mL of AA (n=8) or DP solution. Dialysate and blood samples were taken frequently postinfusion for measurement of AA and DP concentrations as well as AA from DP. RESULTS: Kinetic models were developed for estimation of diffusive mass transport coefficient between peritoneal cavity and blood (K BD), DP hydrolysis rate coefficient (K H) and AA clearance in the body (K C). Calculations showed that K H is about ten times lower than K BD. Thus, hydrolysis rate in peritoneal cavity is much lower than the diffusive transport rate of DP. K BD for AA appeared to be similar to K BD for dipeptides. K C was much higher than K BD for AA. This finding explains the rapid clearance of amino acids from blood. Nevertheless, the AA-based solution resulted in much higher peak concentrations of AA in blood after 120 min of the dwell than AA concentrations achieved following the use of the DP-based solution. CONCLUSIONS: Peritoneal transport characteristics of AA and DP were similar; however their kinetics in blood differs substantially. The DP solution resulted in a less pronounced increase in AA concentrations in blood, suggesting that DP solution could provide AA in a more physiological way.

Distributed model of peritoneal fluid absorption.

The process of water reabsorption from the peritoneal cavity into the surrounding tissue substantially decreases the net ultrafiltration in patients on peritoneal dialysis. The goal of this study was to propose a mathematical model based on data from clinical studies and animal experiments to describe the changes in absorption rate, interstitial hydrostatic pressure, and tissue hydration caused by increased intraperitoneal pressure after the initiation of peritoneal dialysis. The model describes water transport through a deformable, porous tissue after infusion of isotonic solution into the peritoneal cavity. Blood capillary and lymphatic vessels are assumed to be uniformly distributed within the tissue. Starling's law is applied for a description of fluid transport through the capillary wall, and the transport within the interstitium is modeled by Darcy's law. Transport parameters such as interstitial fluid volume ratio, tissue hydraulic conductance, and lymphatic absorption in the tissue are dependent on local interstitial pressure. Numerical simulations show the strong dependence of fluid absorption and tissue hydration on the values of intraperitoneal pressure. Our results predict that in the steady state only approximately 20-40% of the fluid that flows into the tissue from the peritoneal cavity is absorbed by the lymphatics situated in the tissue, whereas the larger (60-80%) part of the fluid is absorbed by the blood capillaries.

Fluid and solute transport in CAPD patients before and after permanent loss of ultrafiltration capacity.

BACKGROUND: Two major types of permanent loss of ultrafiltration capacity (UFC) were previously distinguished among patients treated with CAPD: 1) type HDR with high diffusive peritoneal transport rate of small solutes and low osmotic conductance,but with normal fluid absorption rate, and 2) type HAR with high fluid absorption rate, but with normal diffusive peritoneal transport rate of small solutes and normal osmotic conductance. However, the detailed pattern of changes in peritoneal transport parameters in patients developing loss of ultrafiltration capacity is not known. OBJECTIVE: Analysis of solute and fluid transport parameters in the same patient before and after UFC loss. PATIENTS: Seven CAPD patients who had undergone repeated dwell studies,which were carried out before and/or after the onset of UFC loss. METHODS: Dialysis fluids (2 L) with glucose or a mixture of amino acids as osmotic agent at three basic tonicities were applied during 6 hour dwell studies. Fluid and solute transport parameters were previously shown not to be affected by these dialysis solutions (except by hypertonic amino acid-based solution). Intraperitoneal dialysate volume and fluid absorption rate were assessed using radiolabeled human serum albumin (RISA). Osmotic conductance (a(OS))was estimated by a mathematical model as ultrafiltration rate induced by unit osmolality gradient. Diffusive mass transport coefficients, K(BD), for glucose,urea,and creatinine were estimated using the modified Babb-Randerson-Farrell model. RESULTS: Five patients had increased K(BD) for small solutes after the onset of UFC loss,and three of them had decreased a(OS),whereas two patients had normal a(OS). In one of them, a(OS) decreased with time after the onset of UFC loss with concomitant normalization of glucose absorption. In all studies of these five patients the fluid absorption rate was within the normal range. Two other patients had increased fluid absorption rate (about 5 ml/min),and one of them also had increased K(BD) for small solutes,in two consecutive dwell studies in each patient with the second study being carried out at 1 and 7 months respectively after the first one. In all four studies in these two patients, the a(OS) was within the normal range. The sodium dip during dialysis with 3.86% glucose-based solution was lost, not only among most patients with UFC loss related to reduced osmotic conductance, but also in patients with increased K(BD). CONCLUSIONS: The occurrence of two major types of UFC loss was confirmed. However, a case of a mixed type of UFC loss with high fluid absorption rate and high K(BD) for small solutes, but normal osmotic conductance, and with normalization of initially high K(BD) for small solutes, linked with decreasing initially normal osmotic conductance,was also found. As a reduced sodium dip with hypertonic glucose solution is not only seen in patients with reduced osmotic conductance, it cannot reliably be used as a single measure of decreased aquaporin function. Permanent ultrafiltration capacity loss may be a dynamic phenomenon with a variety of alterations in peritoneal transport characteristics.

Physical and computer modelling of blood flow in a systemic-to-pulmonary shunt.

UNLABELLED: The aim of this work was the application of computer and physical in vitro simulation methods for estimating surgery procedure hemodynamics. The modified Blalock-Taussig (mB-T) palliative surgical procedure is performed to increase the pulmonary blood flow in children with congenital heart defects. Such a systemic-to-pulmonary shunt yields substantial modification in the blood flow within the large blood vessels. The objective of the present study was to investigate basic characteristics of the flow, flow pattern and pressure-flow efficiency, before and after opening of the mB-T graft. METHODS: The model was based on the vessel geometry obtained from the Visible Human Project and included the arch of aorta, the three arteries branching from the arch, the pulmonary trunck, and the left and right pulmonary arteries. The graft was added between the left subclavian artery and the left pulmonary artery. The glass model of the vessels was produced and investigated in a physical model of the cardiovascular system with an artificial ventricular device as the blood pump. Flow rate and hydrostatic pressure were measured at the inlet to and outlets from the glass model and in a few points within the system. Laser flow visualization was also performed. Computer simulations were done using the boundary conditions from the physical model. RESULTS: The opening of the mB-T graft changed flow distribution in all branches (including inflow). A complex flow pattern with large eddies and channelling of the flow in the vicinity of the graft and within it was observed in flow visualization and in computer simulations. Because of that complexity the local measurements of hydrostatic pressure at the vessel wall could not predict the average flow rate. The reversed flow in the graft was observed during the systole. CONCLUSIONS: The complex flow pattern developed in the physical model of the mB-T graft. The channelling of the flow and the formation of large eddies may yield high shear stress and modify blood properties. The rigid wall model can describe only some flow characteristics observed in vivo. Computer simulation is a very fast and accurate method which permits earlier qualification of cardiac surgeons on how to change cardiac vascular blood flow after operations.

Effects of intraperitoneal heparin on peritoneal transport in a chronic animal model of peritoneal dialysis.

BACKGROUND: Heparin has anti-inflammatory effects and is often added to the peritoneal dialysis fluid to prevent fibrin formation. Conjugation of heparin to the surface of biomaterials has been shown to improve its biocompatibility. In this study, we describe for the first time an experimental chronic peritoneal dialysis model with repeated dwell studies in non-uraemic rats and evaluate the effect of addition of heparin to glucose-based peritoneal dialysis fluid on peritoneal fluid and solute transport. METHODS: Wistar male rats, weighing 340+/-15 g, with implanted peritoneal catheters were infused during 1 month, twice per day with 20 ml of Dianeal 1.36%+antibiotics (AB; n = 10) or Dianeal 1.36%+antibiotics+heparin 2500 U/l (HAB; n = 9). After 10 (DS 1) and 30 days (DS 2), a dwell study was performed in rats with free access to drinking water, by infusing 30 ml of Dianeal 3.86%. Dialysate samples were obtained at 0, 2, 30, 60, 120 and 240 min. Blood samples were drawn before and at the end of the dwell. Radiolabelled serum albumin was used as macromolecular volume marker. RESULTS: Peritoneal volumes during DS 1 were significantly greater for the HAB group as compared with the AB group. No differences in ultrafiltration were found during DS 2 for HAB vs AB. However, peritoneal volumes were significantly higher for DS 2 compared with DS 1 in the AB group. The amount of glucose absorbed over time did not differ between the solutions, while fluid absorption tended to be lower in the HAB group. CONCLUSIONS: Heparin may improve peritoneal fluid transport possibly due to better healing and reduced peritoneal inflammation as shown in this novel animal model of chronic peritoneal dialysis with repeated dwell studies.

Kinetic studies of dipeptide-based and amino acid-based peritoneal dialysis solutions.

BACKGROUND: Dipeptide-based peritoneal dialysis solutions may have potential advantages compared with the glucose or amino acid-based solutions. Dipeptides may hydrolyze in the peritoneal cavity, generating constituent amino acids and thereby increasing the osmolality of the dialysate. Dipeptides can also be a valuable source of amino acids, which are poorly soluble in water, such as tyrosine. METHODS: Dwell studies in rats were performed during four hours with dipeptide solutions containing five dipeptides (Gly-His, Ala-Tyr, Thr-Leu, Ser-Phe, Val-Lys), 8, or 16 mmol/L of each dipeptide (low or high dipeptide group). Dwell studies were also performed with a 1.1% amino acid solution (Nutrineal(R)). The model of dipeptide hydrolysis (hydrolysis rate, KH), diffusive (rate constant, KBDD) and convective transport as well as transport of constituent amino acids consisted of mass balance equations, written for each dipeptide and amino acid. RESULTS: Peritoneal volume with the amino acid solution decreased much faster than that with the high and low dipeptide solutions. KH for all dipeptides did not differ between the high and low dipeptide groups. In the low dipeptide group, KH was 0.004 +/- 0.004 mL/min (mean +/- SD) for Gly-His (the lowest) and 0.088 +/- 0.048 mL/min for Thr-Leu (the highest). KBDD was higher than KH for all dipeptides, the average being 0.2 +/- 0.05 mL/min. CONCLUSIONS: Dipeptides are hydrolyzed in the peritoneal cavity, generating constituent amino acids. However, the hydrolysis rate appears to be several times lower than the dipeptide diffusive transport rate from dialysate to blood. Due to the higher molecular weight and intraperitoneal generation of amino acids, the dipeptide-based solutions provide more sustained ultrafiltration than the amino acid solution. The plasma concentration of amino acids at 60 minutes, in relation to the dose of amino acids delivered between 0 and 60 minutes, is considerably higher during the dwells with amino acid-based solution than during dwells with the dipeptide-based solutions.

Errors involved in the application of an imperfect peritoneal volume marker.

Peritoneal volume markers have been used in numerous studies on fluid transport in peritoneal dialysis. The basic assumption used was that the macromolecular marker was stable and that the free fraction of a label (usually radiolabel) was negligibly small. In this study are presented theoretical investigations on the errors involved in application of an imperfect volume marker containing free fraction of a label. These investigations were used in assessing the errors in calculation of peritoneal volume time course, V, and fluid absorption rate (estimated by volume marker clearance, kE) using data from 20 clinical dwell studies with 1.36% Dianeal dialysis solution and radioiodinated human serum albumin as a volume marker. It has been shown that with an in vitro measured 125I free fraction of 2.72%, the error of kE estimation was 11%. However, the maximal error in estimation of V was only 0.2%. In conclusion, the performed analysis implies that calculation of the peritoneal volume time course during the dwell (with correction for the volume marker elimination) is very reliable, and the existence of a free fraction of a volume marker label results in a negligibly small error. However, even small free fraction of the label results in a significant overestimation of the fluid absorption rate.

Transperitoneal transport of glucose in vitro.

The effect of fluid mixing intensification, damage of mesothelial cells, gentamicin, and icodextrin on the diffusive glucose transport across the peritoneal membrane were evaluated in in vitro studies. A mathematical model of mass transport was used to calculate the diffusive permeability, expressed as a diffusive permeability coefficient (P). In the control conditions, the rate of glucose transfer from the interstitial to the mesothelial side of membrane (I-->M) and in the opposite direction (M-->I) remained constant, and the P value at mean was 2,731 +/- 1,493 x 10-4 (cm x s-1). The change of the stirring rate from 5.5 to 11 ml/min increased P values by about 74% for transport direction I-->M and 58% for M-->I, and the change from 11 to 22 ml/min enhanced P at mean by about 42% for both directions. The damage of the mesothelial layer, using sodium deoxycholate (2.5 mmol/L; 103.6 mg%), increased the glucose transfer from the interstitial to the mesothelial side of the peritoneum by 41% and to the opposite direction by 70%. Addition of icodextrin to the glucose solution increased glucose bidirectional transport at mean by about 14% for I-->M and 24% for M-->I. Furthermore, gentamicin did not change the I-->M transfer, but diminished M-->I transport by about 12%. In conclusion, the reduction of unstirred fluid layers at the mesothelium and the interstitium-fluid interfaces, removal of mesothelium, and addition of icodextrin increased the diffusive glucose transport in vitro; unstirred fluid layers restricted glucose transfer (I-->M) more than the mesothelium; and peritoneal glucose transport, directed from the mesothelial to the interstitial side of the peritoneum, decreased slightly after the addition of gentamicin.

Kinetic modeling of fluid and solute transport in peritoneal dialysis.

Mathematical models for fluid and solute transport during peritoneal dialysis are described. A model for the transport of the so-called volume marker enables the correct estimation of the kinetics of the intraperitoneal dialysate volume as well as the rate of peritoneal fluid absorption. On the basis of these estimations, the solute transport components (diffusion, convective solute transport with ultrafiltrate and peritoneal solute absorption) may be separated within the net solute transport using a modified version of the Babb-Randerson-Farrell (BRF) model. The diffusive mass transport coefficient and sieving coefficient are given by the model. A simplified method for the estimation of the diffusive mass transport coefficient during the so-called isovolemia period is also described and compared to the BRF modeling. The three-pore model and the distributed model, which describe the structure-function relationship for the peritoneum, are also addressed.

Effect of peritonitis on peritoneal transport characteristics: glucose solution versus polyglucose solution.

BACKGROUND: Peritonitis is a common clinical problem and contributes to the high rate of technique failure in continuous ambulatory peritoneal dialysis treatment. The present study investigated the effect of peritonitis on peritoneal fluid and solute transport characteristics using glucose and polyglucose (icodextrin) solutions. METHODS: A four-hour dwell was performed in 32 Sprague-Dawley rats (8 rats in each group), with 131I albumin as an intraperitoneal volume marker. Peritonitis was induced by an intraperitoneal injection of 2 mL lipopolysaccharide (100 microg/mL phosphate-buffered saline) four hours before the dwell. Each rat was intraperitoneally infused with 25 mL of 3.86% glucose [glucose solution control group (Gcon) and glucose solution peritonitis group (Gpts)] or 7.5% icodextrin solution [icodextrin solution control group (Pgcon) and icodextrin peritonitis group (PGpts)]. RESULTS: Net ultrafiltration was significantly lower (by 44%) in the Gpts as compared with the Gcon group, but was significantly higher (by 138%) in the PGpts as compared with the PGcon group. The peritoneal fluid absorption rate, including the direct lymphatic absorption rate, was significantly increased (by 78%) in the Gpts group as compared with the Gcon group. However, the total fluid absorption did not differ between the PGpts and the PGcon groups. The dialysate osmolality decreased much faster in the Gpts group as compared with the Gcon group, resulting in significantly lower (by 9%) transcapillary ultrafiltration in the Gpts group. In contrast, the dialysate osmolality increased faster in the PGpts group as compared with the PGcon group, resulting in higher (by 40%) transcapillary ultrafiltration in the PGpts group. The in vitro increase in dialysate osmolality was also higher in the PGpts group as compared with the PGcon group. The solute diffusive transport rates were, in general, increased in the two peritonitis groups as compared with their respective control groups. CONCLUSIONS: Our results suggest the following: (1) Peritonitis results in decreased net ultrafiltration using glucose solution caused by (a) decreased transcapillary ultrafiltration and (b) increased peritoneal fluid absorption. (2) Ultrafiltration induced by the icodextrin solution appears to be related to the increase in dialysate osmolality (mainly because of the degradation of icodextrin). (3) Peritonitis results in increased degradation of icodextrin and a faster increase in dialysate osmolality and therefore better ultrafiltration, whereas the fluid absorption rate does not change. (4) Peritonitis results in increased peritoneal diffusive permeability.

Discriminative impact of ultrafiltration on peritoneal protein transport.

OBJECTIVE: The dialysate concentration of large proteins increases, on average, linearly during the whole peritoneal dialysis dwell, and this linear pattern seems to be independent of the rate of ultrafiltration induced by dialysis fluid. However, we observed a high variability of protein kinetics in individual dwell studies. Therefore, we studied the details of the kinetic pattern of peritoneal transport. DESIGN AND METHODS: Kinetics of beta2-microglobulin, albumin, and total protein was examined in 23 clinically stable continuous ambulatory peritoneal dialysis patients using Dianeal 3.86% (15 dwell studies) or Dianeal 1.36% (9 dwell studies) dialysis fluid. Dialysate volume was measured using radioisotopically labeled albumin as a volume marker, with corrections for sample volume and absorption of fluid and marker from the peritoneal cavity. The generalized version of the Babb-Randerson-Farrell model was applied to estimate diffusive mass transport coefficient (K(BD)) and sieving coefficient (S) for proteins and small solutes (urea, creatinine, glucose, sodium, potassium). To quantify deviations from the linear pattern of protein dialysate concentration increase, the ratio (SR) of the slope of the linear regression line for the initial 3-30 minutes, divided by the slope for the next 60 - 360 minutes, was evaluated for albumin. RESULTS: In 5 dwell studies with Dianeal 3.86% fluid, SR was lower than 1 [low albumin transport (LAT) group, median SR = 0.49, range -4.39 - 0.71], while in the other 10 dwell studies with this solution, SR was higher than 1 [high albumin transport (HAT) group, median SR = 2.77, range 1.32 - 7.56]. Clearances of albumin up to 120 minutes were higher in the HAT group than in the LAT group. The transport of fluid, beta2-microglobulin, and small solutes did not differ between the LAT and the HAT groups. K(BD) values for proteins did not differ between the groups, but S values for albumin and total protein were lower for the LAT group than for the HAT group. A similar diversity was found in the dwell studies with Dianeal 1.36%: In three dwell studies, SR for albumin was lower than 1 (median SR = 0.95, range 0.70 - 0.97), and in six dwells it was higher than 1 (median SR = 1.55, range 1.23 - 1.98). In general, the SR values observed with Dianeal 1.36% were closer to 1 than those for Dianeal 3.86%. CONCLUSIONS: Ultrafiltration may affect the initial kinetic patterns of large protein (such as albumin) transport in two opposing ways: (1) by slowing the increase of protein concentration in dialysate (due to a low sieving coefficient, LAT group), and (2) by speeding up the increase of protein concentration in dialysate (due to a high sieving coefficient, HAT group). The average pattern in a non-selected group of studies is, however, close to a steady (linear) increase.

Effect of blood perfusion on diffusive transport in peritoneal dialysis.

BACKGROUND: Diffusive transport between blood and dialysate during peritoneal dialysis is evaluated in clinical and experimental studies by the diffusive mass transport coefficient, KBD. This global parameter depends on the local diffusive characteristics of the blood capillary wall (permeability) and the tissue, as well as on the density and distribution of capillaries within the tissue. It also depends on the rate of delivery (or washout) of solutes from the tissue with blood flow, that is, on the rate of tissue perfusion. However, the role of blood perfusion in peritoneal transport has not been theoretically evaluated. METHODS: The relationship between the local characteristics of the peritoneal tissue and the global diffusive mass transport coefficient was studied using a new extended version of the distributed model for peritoneal transport, which included the effect of tissue perfusion and capillary surface area on the blood-tissue transport. RESULTS: The solute concentration profiles within the tissue were found to depend on the solute penetration depth, which is equal to the square root of the ratio of the solute diffusivity in tissue to the solute clearance from the capillary bed to tissue. It was shown that KBD might be interpreted as the dialysance of a capillary bed of a characteristic size that would be immersed directly in dialysate. A definition of the effective peritoneal blood flow (EPBF; the blood flow within the tissue layer) was formulated, and it was shown that EPBF depends on the local transport characteristics for the solute. Assuming typical values of the model parameters (known from physiological studies), the values of KBD and EPBF for urea, creatinine, glucose, and CO2 were calculated and compared with the measured values with good qualitative agreement. The transient initial increase of KBD values observed at the beginning of the peritoneal dialysis dwell was interpreted as a transient sixfold increase in tissue perfusion and a twofold increase in the capillary surface area. CONCLUSION: The distributed model can be useful as a theoretical tool for detailed physiological interpretations of changes in peritoneal transport associated with changes in peritoneal microcirculation and structure of the interstitium.

Intraperitoneal addition of hyaluronan improves peritoneal dialysis efficiency.

BACKGROUND: It has been shown that hyaluronan (HA) can decrease peritoneal fluid absorption. It is not known, however, how various molecular weights and various concentrations of hyaluronan affect peritoneal fluid absorption rate. METHODS: A study of 4-hour dwells, with frequent dialysate and blood sampling, was performed in male Sprague-Dawley rats (6-7 rats in each group) with 131I albumin as an intraperitoneal volume marker. Each rat was infused intraperitoneally with 25 mL of 1.5% glucose solution alone or 1.5% glucose solution containing hyaluronan at various molecular weights (MW-85 kD, 280 kD, 500 kD, and 4 MD) or containing hyaluronan of MW 500 kD at various concentrations (0.01%, 0.05%, 0.1%, 0.5%). Two additional groups were infused with 40 mL of 1.36% glucose dialysate alone or 1.36% glucose dialysate with 0.01% hyaluronan (MW 500 kD) to test the effect of hyaluronan when high dialysate fill volume was used. RESULTS: Addition of 0.01% hyaluronan significantly decreased peritoneal fluid absorption rate (K(E)) (by 22%, p < 0.01). The decrease was more marked with hyaluronan at high MW or high concentration, or with high dialysate fill volume. The net ultrafiltration tended to be higher in all hyaluronan groups compared to their control groups except in the 4 MD group; this difference was mainly due to a lower K(E) in all the hyaluronan groups. The direct lymphatic flow was significantly decreased in the 0.5% HA group. The transcapillary ultrafiltration rate (Qu) was significantly lower in the 4 MD group as compared to the control group. No difference in Qu was found between the other groups as compared to their control groups. CONCLUSIONS: (1) Intraperitoneal addition of hyaluronan may increase net peritoneal fluid removal, mainly because hyaluronan decreases peritoneal fluid absorption rate. The decrease was more marked when high dialysate fill volume was used, indicating that intraperitoneal addition of hyaluronan can prevent the decreased net ultrafiltration caused by an increase in dialysate fill volume. (2) The decrease in peritoneal fluid absorption rate may be both MW-dependent and concentration-dependent: that is, a higher MW as well as a higher concentration of hyaluronan result in a more marked decrease in peritoneal fluid absorption rate. (3) Low concentrations of high MW hyaluronan may also decrease Qu. However, Qu did not decrease when high concentrations of hyaluronan were used despite a significant decrease in peritoneal fluid absorption rate.

Mathematical models for peritoneal transport characteristics.

Four mathematical models and for the description of peritoneal transport of fluid solutes are reviewed. The membrane model is usually applied for (1) separation of transport components, (2) formulation of the relationship between flow components and their driving forces, and (3) estimation of transport parameters. The three-pore model provides correct relationships between various transport parameters and demonstrates that the peritoneal membrane should be considered heteroporous. The extended three-pore model discriminates between heteroporous capillary wall and tissue layer, which are assumed to be arranged in series; the model improves and modifies the results of the three-pore model. The distributed model includes all parameters involved in peritoneal transport and takes into account the real structure of the tissue with capillaries distributed at various distances from the surface of the tissue. How the distributed model may be applied for the evaluation of the possible impact of perfusion rate on peritoneal transport, as recently discussed for clinical and experimental studies, is demonstrated. The distributed model should provide theoretical bases for the application of other models as approximate and simplified descriptions of peritoneal transport. However, an unsolved problem is the theoretical description of bi-directional fluid transport, which includes ultrafiltration to the peritoneal cavity owing to the osmotic pressure of dialysis fluid and absorption out of the peritoneal cavity owing to hydrostatic pressure.

A simple and fast method to estimate peritoneal membrane transport characteristics using dialysate sodium concentration.

BACKGROUND: The peritoneal equilibration test (PET) is widely used to classify a patient's peritoneal transport characteristics. However, PET is laborious and the prediction of fluid removal based on PET is generally poor. It is believed that osmosis by glucose occurs partially through transcellular water channels, resulting in sieving of sodium and decrease of dialysate sodium concentration when using hypertonic glucose dialysate. OBJECTIVE: In this study, we investigated the possibility of using dialysate sodium concentration to classify the patient's peritoneal transport characteristics. METHODS: A 6-hour dwell study with frequent dialysate and plasma sampling was performed in 46 patients using 2 L of 3.86% glucose dialysate with 131I-albumin as an intraperitoneal volume (IPV) marker. The peritoneal transport of sodium, creatinine, glucose, and fluid was evaluated. RESULTS: The dialysate sodium concentration at 240 min (D(Na240)) significantly correlated with D/P creatinine (r = 0.76, p < 0.001) and D/D0 glucose (r = -0.83, p < 0.001) at 240 min of the dwell (better than dialysate sodium concentration at any other time of the dwell). DNa240 also significantly correlated with IPV at 240 min of the dwell (r = -0.61, p < 0.001)(better than D/P creatinine and D/D0 glucose). There were significant correlations between D(Na240) and the sodium-sieving coefficient (r = 0.71, p < 0.001) and the diffusive mass transfer coefficient for sodium (r = 0.50, p < 0.001). When using D(Na240) to divide the patients into four groups, as in the PET method, no significant difference was found between the two methods. CONCLUSION: Using 3.86% glucose solution, D(Na240) can be used instead of D/P creatinine to classify patients into different transport groups. D(Na240) provides a better prediction of peritoneal fluid transport and reflects both the diffusive and convective transport properties of the membrane. As only one dialysate sample (and no blood sample) is needed, D(Na240) may offer important clinical advantages compared with PET.