Evaluation of loss of active heparin in the peritoneal cavity during intermittent peritoneal dialysis]

Our studies aimed at determining a loss of active heparin from the peritoneal cavity after its intraperitoneal administration (250 JU/l of dialysis fluid) in 16 patients treated because of the end-stage renal failure with intermittent peritoneal dialysis and at comparing heparin influx clearance with that of glucose. It has been shown that heparin used in this dose loses 60-70% of its activity after 20-minute equilibration of dialysis fluid in the peritoneal cavity. Heparin influx clearance is higher than that of glucose but it depends on utilization of heparin in peritoneal cavity rather than on its penetration to the blood circulation.     

Liposome supported peritoneal dialysis in rat amitriptyline exposure with and without intravenous lipid emulsion

Liposome supported peritoneal dialysis is a recently described technique which may eventually be applicable in the clinical scenario of the intoxicated patient. We evaluated the hypothesis that intravenous injection of lipid emulsion (ILE) would augment acidic pH gradient liposome supported peritoneal dialysis (LSPD). Orogastrically amitriptyline dosed rats were treated with either Sodium bicarbonate (NaHCO3) intravenously and standard intraperitoneal dialysate (Group A); NaHCO3 intravenously and LSPD (Group B); or ILE and LSPD (Group C). The primary endpoint was dialysate amitriptyline concentration after a 60?min dwell. Secondary analysis included an estimate of extraction ratio for peritoneal blood flow (ERs). There were significantly higher intraperitoneal concentrations of amitriptyline and ERs in the two groups treated with LSPD (Group B, p?=?0.02, Group C, p?<?0.01 vs. Group A). There was no observed effect for ILE on intraperitoneal amitriptyline concentration or ERs (p?>?0.20). LSPD increased the amitriptyline concentration in peritoneal dialysate. No further increase was demonstrated with ILE. This may be either because such an effect is absent, or type II error. Exploratory analysis suggests LSPD may be driven by total rather than free drug concentrations.     

Relationship between interstitial fluid volume and pressure (compliance) in hypothyroid rats

There is clinical and experimental evidence that lack of thyroid hormones may affect the composition and structure of the interstitium. This can influence the relationship between volume and pressure during changes in hydration. Hypothyrosis was induced in rats by thyroidectomy 8 wk before the experiments. Overhydration was induced by infusion of acetated Ringer, 5, 10, and 20% of the body weight, while fluid was withdrawn by peritoneal dialysis with hypertonic glucose. Interstitial fluid pressure (P(i)) in euvolemia (euvolemic control situation) and experimental situation was measured with micropipettes connected to a servocontrolled counterpressure system. The corresponding interstitial fluid volume (V(i)) was found as the difference between extracellular fluid volume measured as the distribution volume of (51)Cr-labeled EDTA and plasma volume measured using (125)I-labeled human serum albumin. In euvolemia, V(i) was similar or lower in the skin and higher in skeletal muscle of hypothyroid than in euthyroid control rats, whereas the corresponding P(i) was higher in all tissues. During overhydration, P(i) rose to the same absolute level in both types of rats, whereas during peritoneal dialysis there was a linear relationship between volume and pressure in all tissues and types of rats. Interstitial compliance (C(i)), calculated as the inverse value of the slope of the curve relating changes in volume and pressure in dehydration, did not differ significantly in the hindlimb skin of hypothyroid and euthyroid rats. However, in skeletal muscle, C(i) was 1.3 and 2.0 ml. 100 g(-1). mmHg(-1) in hypothyroid and euthyroid rats (P < 0.01), with corresponding numbers for the back skin of 2.7 and 5.0 ml. 100 g(-1). mmHg(-1) (P < 0.01). These experiments suggest that lack of thyroid hormones in rats changes the interstitial matrix, again leading to reduced C(i) and reduced ability to mobilize fluid from the interstitium.     

Quantitation of dextran 70 in peritoneal dialysate from patients administered 7.5% polyglucose

A method using gel permeation chromatography was evaluated for the quantitation of dextran 70 in dialysate samples containing polyglucose. Dialysate samples containing dextran 70 and polyglucose were pretreated using the enzyme α-amylase to selectively hydrolyze the α(1–4)-linked polyglucose, while leaving the α(1–6)-linked dextran 70 intact. Following sample deproteinization with trichloroacetic acid, dextran 70 was quantitated using gel permeation chromatography with refractive index detection. This method was evaluated for accuracy, precision, specificity, linearity, range, and analyte stability. Adequate method linearity with a correlation of >0.999 was established over the range of dextran 70 concentration from 1 to 0.025 mg/ml. Method precision was approximately 2% R.S.D. and accuracy (% recovery) was approximately 98–100% in the typical sample concentration range (1–0.5 mg/ml). This method was applied to the determination of intraperitoneal fluid kinetics in continuous ambulatory peritoneal dialysis (CAPD) patients administered daily night-time intraperitoneal exchanges with either 7.5% polyglucose or 4.25% dextrose. Dextran 70 was added to the dialysis solutions to yield an initial concentration of 1 mg/ml. Dialysate samples were collected at various times over a 10-h dwell-time and assayed for dextran 70. Intraperitoneal volume profiles based on dextran 70 concentrations and drain volumes were then calculated for each dialysis solution.     

Reliable determination of furosine in human serum and dialysate proteins by high-performance liquid chromatography

Furosine, formed by hydrolysis of 1-deoxy-fructosyl-lysine (fructose-lysine), is a product of the Amadori rearrangement of glucose and ϵ-NH₂-lysine. Fructose-lysine can react further with tissue and circulating proteins to produce advanced glycation end-products (AGEs). Peritoneal dialysate used in the treatment of patients with end-stage renal failure contains high concentrations of glucose which may lead to intraperitoneal formation of AGEs. To quantitate the kinetics of formation and peritoneal clearance of glycated peritoneal dialysate proteins, we developed an effective approach to the measurement of furosine in clinical samples of serum and peritoneal dialysate.     

Glycosylated Hemoglobin and Albumin-Corrected Fructosamine Are Good Indicators for Glycemic Control in Peritoneal Dialysis Patients

Purpose

Diabetes mellitus (DM) is the most common cause of end-stage renal disease and is an important risk factor for morbidity and mortality after dialysis. However, glycemic control among such patients is difficult to assess. The present study examined glycemic control parameters and observed glucose variation after refilling different kinds of fresh dialysate in peritoneal dialysis (PD) patients.

Methods

A total of 25 DM PD patients were recruited, and continuous glucose monitoring system (CGMS) was applied to measure interstitial fluid (ISF) glucose levels at 5-min intervals for 3 days. Patients filled out diet and PD fluid exchange diaries. The records measured with CGMS were analyzed and correlated with other glycemic control parameters such as fructosamine, albumin-corrected fructosamine (AlbF), glycosylated hemoglobin (HbA1c), and glycated albumin levels.

Results

There were significant correlations between mean ISF glucose and fructosamine (r = 0.45, P<0.05), AlbF (r = 0.54, P<0.01), and HbA1c (r = 0.51, P<0.01). The ISF glucose levels in glucose-containing dialysate increased from approximately 7–8 mg/dL within 1 hour of exchange in contrast to icodextrin dialysate which kept ISF glucose levels unchanged.

Conclusion

HbA1c and AlbF significantly correlated with the mean ISF glucose levels, indicating that they are reliable indices of glycemic control in DM PD patients. Icodextrin dialysate seems to have a favorable glycemic control effect when compared to the other glucose-containing dialysates.     

An experimental, non-uremic rabbit model of peritoneal dialysis

Peritoneal dialysis (PD) is a well established method of depuration in uremic patients. Standard dialysis solutions currently in use are not biocompatible with the peritoneal membrane. Studying effects of dialysate on peritoneal membrane in humans is still a challenge. There is no consensus on the ideal experimental model so far. We, therefore, wanted to develop a new experimental non-uremic rabbit model of peritoneal dialysis, which would be practical, easy to conduct, not too costly, and convenient to investigate the long-term effect of dialysis fluids. The study was done on 17 healthy Chinchilla male and female rabbits, anesthetized with Thiopental in a dose of 0.5 mg/kg body mass. A catheter, specially made from Tro-soluset (Troge Medical GMBH, Hamburg, Germany) infusion system, was then surgically inserted and tunneled from animals' abdomen to their neck. The planned experimental procedure was 4 weeks of peritoneal dialysate instillation. The presented non-uremic rabbit model of peritoneal dialysis is relatively inexpensive, does not require sophisticated technology and was well tolerated by the animals. Complications such as peritonitis, dialysis fluid leakage, constipation and catheter obstruction were negligible. This model is reproducible and can be used to analyze the effects of different dialysis solutions on the rabbit peritoneal membrane.     

中医药防治腹膜纤维化的研究进展

腹膜透析是治疗终末期肾脏病较为有效的方法之一,但是腹膜长期暴露于非生理性的腹膜透析液中（低pH、高浓度葡萄糖以及高渗透压等）会致腹膜纤维化,从而导致腹膜结构和功能的丧失,这是患者放弃腹膜透析的原因之一。现代药理学实验证明,中医药对于腹膜纤维化的防治研究主要集中在腹膜间皮细胞的上皮间质转化方面,通过对细胞因子的作用,保护和／或改善腹膜间皮细胞的功能防治腹膜纤维化。     

Gas Exchange in Renal Failure: II—Pulmonary Gas Exchange during Peritoneal Dialysis

Blood gas analysis studies have been made in patients undergoing peritoneal dialysis. It has been shown that oxygen tensions are reduced when fluid has been run into the peritoneal cavity and that this fall in Pao₂ is reversed after running out the dialysate. The change in Pao₂ is greater with 2-litre than with 1-litre cycles.     

Effect of glucose concentration on peritoneal inflammatory cytokines in continuous ambulatory peritoneal dialysis patients

OBJECTIVE: It is known that glucose concentrations of peritoneal dialysis solutions are detrimental to the peritoneal membrane. In order to determine the effect of glucose concentration on cytokine levels of peritoneal fluid of continuous ambulatory peritoneal dialysis (CAPD) patients, a cross-sectional study was performed. METHODS: Nine non-diabetic CAPD patients participated in two 8-h dwell sessions of overnight exchanges in consecutive days, with 1.36% and 3.86% glucose containing peritoneal dialysis solutions (Baxter-Eczacibas). Peritoneal dialysis fluid tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 levels were measured. RESULTS: TNF-alpha levels after 1.36% and 3.86% glucose used dwells were 23+/-14 pg/ml and 28+/-4 pg/ml, respectively (p=0.78). The IL-6 levels were 106+/-57 pg/ml and 115+/-63 pg/ml (p=0.81), respectively. CONCLUSION: In our in vivo study we found that the glucose concentration of the conventional lactate-based CAPD solution has no effect on basal IL-6 and TNF-alpha levels of peritoneal fluid. Further in vivo studies with non-lactate-based CAPD solutions are needed in order to determine the effect of glucose concentration per se on cytokine release.     

A computational study of systemic hydration in vocal fold collision

Mechanical stresses develop within vocal fold (VF) soft tissues due to phonation-associated vibration and collision. These stresses in turn affect the hydration of VF tissue and thus influence voice health. In this paper, high-fidelity numerical computations are described, taking into account fully 3D geometry, realistic tissue and air properties, and high-amplitude vibration and collision. A segregated solver approach is employed, using sophisticated commercial solvers for both the VF tissue and glottal airflow domains. The tissue viscoelastic properties were derived from a biphasic formulation. Two cases were considered, whereby the tissue viscoelastic properties corresponded to two different volume fractions of the fluid phase of the VF tissue. For each case, hydrostatic stresses occurring as a result of vibration and collision were investigated. Assuming the VF tissue to be poroelastic, interstitial fluid movement within VF tissue was estimated from the hydrostatic stress gradient. Computed measures of overall VF dynamics (peak airflow velocity, magnitude of VF deformation, frequency of vibration and contact pressure) were well within the range of experimentally observed values. The VF motion leading to mechanical stresses within the VFs and their effect on the interstitial fluid flux is detailed. It is found that average deformation and vibration of VFs tend to increase the state of hydration of the VF tissue, whereas VF collision works to reduce hydration.     

Description of hydration free energy density as a function of molecular physical properties

A method to calculate the solvation free energy density (SFED) at any point in the cavity surface or solvent volume surrounding a solute is proposed. In the special case in which the solvent is water, the SFED is referred to as the hydration free energy density (HFED). The HFED is described as a function of some physical properties of the molecules. These properties are represented by simple basis functions. The hydration free energy of a solute was obtained by integrating the HFED over the solvent volume surrounding the solute, using a grid model. Of 34 basis functions that were introduced to describe the HFED, only six contribute significantly to the HFED. These functions are representations of the surface area and volume of the solute, of the polarization and dispersion of the solute, and of two types of electrostatic interactions between the solute and its environment. The HFED is described as a linear combination of these basis functions, evaluated by summing the interaction energy between each atom of the solute with a grid point in the solvent, where each grid point is a representation of a finite volume of the solvent. The linear combination coefficients were determined by minimizing the error between the calculated and experimental hydration free energies of 81 neutral organic molecules that have a variety of functional groups. The calculated hydration free energies agree well with the experimental results. The hydration free energy of any other solute molecule can then be calculated by summing the product of the linear combination coefficients and the basis functions for the solute.     

含蛋白转导域的SARA/SBD融合蛋白对腹膜透析大鼠

目的：探讨含蛋白转导域的SARA融合蛋白（PTD-SAR／SBD）对腹膜透析大鼠腹膜纤维化的抑制作用。方法：每日腹腔注射4．25％葡萄糖腹膜透析液（PDF）制备腹膜透析大鼠模型。28只Sprague-Dawley大鼠随机分为正常对照组（n=8）;腹膜透析模型组（n=10）;PTD-SARA／SBD蛋白干预组（n=10）。4周后行腹膜平衡试验,检测超滤量、葡萄糖吸收率;留取壁层腹膜组织行HE染色;免疫组织化学方法检测大鼠壁层腹膜间皮细胞转分化指标E-cadherin和Twist的表达;Westemblotting测定E-cadherin、twist,以及CollagenⅠ、TGF-β1、P-Smad3、t-Smad3的表达。结果：①与正常对照组比较,模型组大鼠壁层腹膜增厚,糖转运率增加,超滤量降低（P〈0．01）;免疫组织化学与westernblotting检测结果显示E-cadherin表达下调,Twist表达上调;CollagenⅠ、P-Smad3、TGF-β1表达增加。②与模型组比较,PTD-SARA／SBD蛋白干预组大鼠壁层腹膜糖转运率降低,超滤量增加（P〈0．05）;E-cadherin表达上调,Twist表达下调;CollagenⅠ、TGF-β1、P-Smad3表达减少,各组t-Smad3无明显变化。结论：PTD-SARA／SBD融合蛋白通过抑制TGF-WSmads信号通路部分逆转腹膜间皮细胞转分化从而改善腹膜结构和功能,为防治腹膜透析所致腹膜纤维化奠定基础。     

Calcitriol decreases TGF-β1 and angiotensin II production and protects against chlorhexide digluconate-induced liver peritoneal fibrosis in rats

Peritoneal fibrosis is a major complication of peritoneal dialysis that can lead to ultrafiltration failure. This study investigates the protective effects of calcitriol on chlorhexidine digluconate-induced peritoneal fibrosis in rats. Peritoneal fibrosis was induced in Sprague-Dawley rats by daily administration of 0.5 mL 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis for 1 week. Rats received daily intravenous injections of calcitriol (low-dose, 10 ng/kg; or high-dose, 100 ng/kg) for 1 week. After 7 days, conventional 4.25% Dianeal (30 mL) was administered via peritoneal dialysis over 4 h. Peritoneal solute transport was calculated from the dialysate concentration relative to its concentration in the initial infused dialysis solution (D₄/D_{0 glucose}) for glucose, and the dialysate-to-plasma concentration ratio (D₄/P_{4 urea}) at 4 h for urea. Rats were then sacrificed and the liver peritoneum was harvested for immunohistochemical analysis via microscopy. After dialysis, the D₄/P_{4 Urea} level was reduced; increases were observed in the D₄/D_{0 glucose} level and the levels of active transforming growth factor-β1 and angiotensin II in serum and dialysate; the liver peritoneum and muscle peritoneum was markedly thickened, and the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and phosphorylated Smad2/3 (P-Smad2/3)-positive cells in the liver peritoneum was elevated in the peritoneal fibrosis group compared with the vehicle group. Calcitriol decreased the serum and dialysate active transforming growth factor-β1 and angiotensin II level, decreased the thickness of the liver peritoneum and muscle peritoneum, and decreased the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and P-Smad2/3-positive cells in liver peritoneum cells. High-dose calcitriol exhibited better protective effects against peritoneal fibrosis than did the lower dose. Calcitriol protected against chlorhexidine digluconate-induced peritoneal fibrosis in rats by decreasing transforming growth factor-β1 and angiotensin II production.     

Severe hypoglycaemia due to combined use of parenteral nutrition and renal dialysis.

A 24-year-old woman who had sustained serious injuries in a road traffic accident required renal dialysis daily and was fed intravenously with a solution containing 25% dextrose. Subsequently insulin had to be added to the parenteral fluid to maintain blood glucose concentrations at physiological values. On one occasion parenteral feeding was continued until dialysis was started; she became comatose and the plasma glucose concentration was found to be less than 1 mmol/l (18 mg/100 ml). She responded rapidly to a 50 ml intravenous bolus of 50% dextrose. When parenteral feeding and dialysis are used simultaneously glucose passes across the semi-permeable membrane from the blood to the dialysate so that hypoglycaemia may occur. Insulin added to the parenteral fluid further decreases blood glucose concentrations. Stopping parenteral feeding 30-45 minutes before dialysis is started eliminates this danger of hypoglycaemia.     

Gender-specific response to interstitial angiotensin II in human white adipose tissue.

Angiotensin II is synthesized locally in various tissues. However, the role of interstitial angiotensin II in the regulation of regional metabolism and tissue perfusion has not as yet been clearly defined. We characterized the effect of interstially applied angiotensin II in abdominal subcutaneous adipose tissue of young, normal-weight, healthy men (n = 8) and women (n = 6) using the microdialysis technique. Adipose tissue was perfused with 0.01, 0.1, and 1 micro M angiotensin II. Dialysate concentrations of ethanol, glycerol, glucose, and lactate were measured to assess changes in blood flow (ethanol dilution technique), lipolysis, and glycolysis, respectively. Baseline ethanol ratio and dialysate lactate were both significantly higher, whereas dialysate glucose was significantly lower in men vs. women. In men, ethanol ratio and dialysate glucose, lactate and glycerol did not change significantly during perfusion with angiotensin II. In women, however, angiotensin II induced a significant increase in ethanol ratio and dialysate lactate and a decrease in dialysate glucose close to values found for men and this response was almost maximal at the lowest angiotensin II concentration used. Dialysate glycerol did not change significantly. We conclude that baseline blood flow and glucose supply and metabolism is significantly higher in women than in men. In men, interstitial Ang II has only a minimal effect on adipose tissue blood flow and metabolism. In women, however, a high physiological concentration of interstitial angiotensin II can reduce blood flow down to values found in men. This is associated with an impaired glucose supply and metabolism. Additionally, Ang II inhibits lipolysis.     

Natriuresis and carbohydrate-induced antinatriuresis in fasted, hydrated hypertensives.

After an overnight fast and oral hydration with water, hypertensive subjects developed a significant natriuresis (mean urine sodium excretions increased from 130 to 291 mueq/min. The incidence of a natriuresis (greater than 200 mueq sodium excreted per minute) was 75% in the hypertensive group (16 subjects) compared to 27% in a previously studied normotensive group (22 subjects). The incidence of a carbohydrate-induced antinatriuresis (greater than 30% decrease in urinary sodium excretion) was 62% in the hypertensive group compared to 41% in the normotensive group. No decrease in plasma volume (131I-labeled albumin concentration) due to a shift of solute and water intracellularly could be documented to explain the antinatriuretic effect of glucose. An incidental observation was a significant decrease in plasma zinc concentrations after glucose ingestion.     

Intraperitoneal insulin in uraemic diabetics undergoing continuous ambulatory peritoneal dialysis.

The kinetics of absorption of intraperitoneally administered insulin were studied in nine uraemic insulin-dependent diabetics undergoing continuous ambulatory peritoneal dialysis (CAPD). In each of three studies 20 U of regular insulin was directly injected as a bolus into the peritoneal cavity through an indwelling Tenckhoff catheter. In two procedures the insulin injection was followed by the instillation of either 2 litres of 1.5% dextrose dialysates or 2 litres of 4.5% dextrose dialysate. In the third 20 ml of saline was used to flush the tubing. Plasma free insulin values rose more rapidly and reached significantly higher concentrations (55.6 +/- 18.8 mU/l) when the insulin had been injected into an empty peritoneal cavity than when it was followed by dialysate. These differences were observed despite the fact that most of the insulin injected was retained by the patients. Since the plasma insulin values did not differ after instillations of dialysate containing 1.5% and 4.5% dextrose, the osmolality of the dialysate seemed not to affect insulin absorption, and the dilution of the insulin probably delayed its transfer through the peritoneum. These findings suggest that insulin given intraperitoneally to patients undergoing CAPD will be most effective if it is given into an empty peritoneal cavity at least 30 minutes before the dialysate is instilled.     

MMP-7 affects peritoneal ultrafiltration associated with elevated aquaporin-1 expression via MAPK/ERK pathway in peritoneal mesothelial cells

Peritoneal membrane dysfunction and the resulting ultrafiltration failure are the major disadvantages of long-term peritoneal dialysis (PD). It becomes increasingly clear that mesothelial cells play a vital role in the pathophysiological changes of the peritoneal membrane. Matrix metalloproteinases (MMPs) function in the extracellular environment of cells and mediate extracellular matrix turnover during peritoneal membrane homeostasis. We showed here that dialysate MMP-7 levels markedly increased in the patients with PD, and the elevated MMP-7 level was negatively associated with peritoneal ultrafiltration volume. Interestingly, MMP-7 could regulate the cell osmotic pressure and volume of human peritoneal mesothelial cells. Moreover, we provided the evidence that MMP-7 activated mitogen-activated protein kinases (MAPKs)-extracellular signal-regulated kinase 1/2 (ERK) pathway and subsequently promoted the expression of aquaporin-1 (AQP-1) resulting in the change of cell osmotic pressure. Using a specific inhibitor of ERK pathway abrogated the MMP-7-mediating AQP-1 up-regulation and cellular homeostasis. In summary, all the findings indicate that MMP-7 could modulate the activity of peritoneal cavity during PD, and dialysate MMP-7 might be a non-invasive biomarker and an alternative therapeutic target for PD patients with ultrafiltration failure.