The Effect of Colchicine on the Peritoneal Membrane

Peritoneal dialysis (PD) is a treatment modality for patients with renal failure. Peritoneal fibrosis is one of the most serious complications after long-term continuous ambulatory peritoneal dialysis (CAPD). Histological studies in both humans and animals show that chronic peritoneal dialysis results in fibrosis of the peritoneal membrane. In our study, we investigated the effect of colchicine on peritoneal alterations induced by hypertonic PD solution in rats. Sprague-Dawley rats intraperitoneally received saline (control group) once daily, for 28 days, or 3.86% glucose (PDF group), or 3.86% glucose plus colchicine (colchicine group). Animals from each group were sacrificed after 28 days with anesthetized ketamine (60 mg/kg BW). For the PD fluid assessment, 1 h before the sacrifice of animals, 10 mL PD fluid of 2.27% glucose was given, and this fluid was obtained after the sacrifice. The levels of transforming endothelial growth factor β (TGF-β), tumor necrosis factor α (TNF-α) and albumin were investigated both in the peritoneal dialysate and blood, and the levels of malondialdehyde (MDA) were investigated only in peritoneal dialysate. The peritoneal membrane was evaluated histologically by light microscopy. When groups were compared in terms of body weight change, the colchicine group significantly lost weight compared to controls and PDF group (?4.7% ± 4.5, 3.5% ± 7.2, 3.0% ± 1.3, respectively, p = 0.018). Also, the blood albumin level was significantly lower for these in the colchicine group compared to those in the PDF group (2.7 ± 0.35 versus 3.2 ± 0.3 g/dL, respectively, p = 0.048). The blood TGF-β level was significantly lower in the control group, and no difference was observed between the PDF and colchicine groups (294.4 ± 67.5 versus 787.4 ± 237.4 versus 615.3 ± 235.1 pg/mL, respectively, p = 0.004). The mesothelial thickness found in groups was as follows: control group 102 ± 18.9 µm, PDF group 128.33 ± 33.1 µm, colchicine group 117 ± 35.6 µm (p = 0.34). In conclusion, a rat model for peritoneal dialysis associated peritoneal derangement without fibrosis could be induced. Colchicine could not prevent peritoneal derangement in this model.     

Effects of atorvastatin on development of peritoneal fibrosis in rats on peritoneal dialysis

Rational: Peritoneal sclerosis is one of the important complications of long-term peritoneal dialysis (PD). In this study, efficacy of atorvastatin on peritoneal histology and functions in non-uremic rats on PD was tested. Objectives: Twenty-two non-uremic Wistar albino rats were randomized into three groups: Sham (intraperitoneal saline), peritoneal dialysis (PD, intraperitoneal 3.86% dextrose containing PD solution), and treatment (TX, intraperitoneal 3.86% dextrose containing PD solution plus atorvastatin added into drinking water). At the end of a 4-week period, 1 h peritoneal equilibration test was performed. Serum lipids and certain cytokines, mediators, markers, and antioxidant enzyme activities in serum and dialysate were studied. Peritoneal thickness was measured and peritoneal inflammation, fibrosis, and vascular proliferation were scored in histological sections. Main findings: In histological examinations, inflammation, fibrosis, and vascular proliferation were significantly more frequent in PD group than Sham group and it seemed to decrease significantly when atorvastatin was used in conjunction with PD. Additionally, peritoneum was significantly thicker in PD group when compared to that of Sham and TX groups. Serum parameters did not significantly differ between groups. On the other hand, dialysate glutathione reductase (GR) activity and TGF-β were significantly lower in TX group than that of the PD group, whereas dialysate IL-6 level was higher in TX group. Principal conclusions: In our study, atorvastatin use appeared to diminish structural changes in peritoneum. Decreased expression of TGF-β in dialysate may be one of the possible underlying mechanisms.     

Comparison of peritoneal equilibration test with 2.27% and 3.86% glucose dialysis solution

BACKGROUND: The standard Peritoneal Equilibration Test (PET) uses a 2.27% glucose dialysis solution in peritoneal dialysis (PD). A more hypertonic solution (3.86%) has recently been proposed to obtain further information about ultrafiltration (UF). AIM: To compare results in terms of peritoneal solute transport (4h-dialysate-to-plasma ratio, 4h-D/P) between 2.27% and 3.86% PET. DESIGN: 23 patients on PD were randomized to form two groups, A and B. A 2.27% dextrose 2-L exchange was used in group A, followed on the same day by a 3.86% dextrose 2-L exchange, both with a 4-hour dwell (2.27% and 3.86% PET); in group B, the same treatment was administered in reverse. 4h-D/P of urea, creatinine and sodium at time 0, 60, 120 and 240 minutes and net UF were calculated for each PET and compared. RESULTS: No significant statistical differences were found for the usual peritoneal transport indexes, 4h-D/P of urea and creatinine, between 2.27% and 3.86% PET, which produced almost identical results. The creatinine 4h-D/P were 0.67+/-0.09 vs. 0.66+/-0.10 (p= NS) and the urea 4h-D/P 0.91+/-0.04 vs. 0.90+/-0.04 (p= NS). The sodium D/P was lower at all times during the 3.86% PET: D/P60= 0.92+/-0.05 vs. 0.88+/-0.03, D/P120= 0.91+/-0.02 vs. 0.87+/-0.03, D/P240= 0.92+/-0.02 vs. 0.88+/-0.04 (p< 0.0001). The net UF was 478 +/- 175 vs. 936 +/- 233 mL respectively (p< 0.0001). CONCLUSION: Our study suggests that a 3.86% PD solution could be used for PET instead of the 2.27% solution in order to assess peritoneal solute transport, as well as UF, while obtaining almost identical results as the 2.27% solution.     

Volume stress-induced peritoneal endothelin-1 release in continuous ambulatory peritoneal dialysis

In long-term peritoneal dialysis, functional deterioration of the peritoneal membrane is often associated with proliferative processes of the involved tissues leading to peritoneal fibrosis. In continuous ambulatory peritoneal dialysis (CAPD), failure to achieve target values for adequacy of dialysis is commonly corrected by increasing dwell volume; in case of ultrafiltration failure, osmolarity of the dialysate gets increased. In a prospective study, the impact of increasing dwell volume from 1500 ml to 2500 ml per dwell (volume trial) or changing the osmolarity of the dialysate from 1.36 to 3.86% glucose (hyperosmolarity trial) on the peritoneal endothelin-1 (ET-1) release was analyzed. ET-1 is known to exert significant proliferative activities on a variety of cell types leading to an accumulation of extracellular matrix. A highly significant difference in the cumulative peritoneal ET-1 synthesis was found between the low- and high-volume exchange, whereas differences in the hyperosmolarity setting were only moderate. Sixty minutes after initiating dialysis, the cumulative ET-1 synthesis was 2367 +/- 1023 fmol for the 1500 ml versus 6062 +/- 1419 fmol for the 2500 dwell (P < 0.0001) and 4572 +/- 969 fmol versus 6124 +/- 1473 fmol for the 1.36 and 3.86% glucose dwell (P < 0.05), respectively. In conclusion, increasing dwell volume leads to a strong activation of the peritoneal paracrine endothelin system. Because ET-1, apart from being a potent vasoactive peptide, contributes to fibrotic remodeling, this study indicates that volume stress-induced ET-1 release might contribute to structural alteration of the peritoneal membrane in long-term peritoneal dialysis.     

High peritoneal residual volume decreases the efficiency of peritoneal dialysis

BACKGROUND: Wide variation in peritoneal residual volume (PRV) is a common clinical observation. High PRV has been used in both continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis to minimize the time of a dry peritoneal cavity and to achieve better dialysis. However, the impact of PRV on peritoneal transport is not well established. In this study, we investigated the effect of PRV on peritoneal transport characteristics. METHODS: Peritoneal effluents were collected in 32 male Sprague-Dawley rats after a five-hour dwell with 1.36% glucose solution. Forty-eight hours later, a four hour dwell using 25 ml of 3.86% glucose solution and frequent dialysate and blood sampling was done in each rat with 125I-albumin as a volume marker. Before the infusion of the 3.86% glucose solution, 0 (control), 3, 6, or 12 ml (8 rats in each group) of autologous effluent (serving as PRV) was infused to the peritoneal cavity. RESULTS: After subtracting the PRV, the net ultrafiltration was significantly lower in the PRV groups as compared with the control group: 13.4 +/- 0.5, 12.0 +/- 1.0, 11.7 +/- 1.7, and 8.9 +/- 0.4 ml for 0, 3, 6, and 12 ml PRV groups, respectively (P < 0.001). The lower net ultrafiltration associated with higher PRV was due to (a) a significantly lower transcapillary ultrafiltration rate (Qu) caused by a lower osmotic gradient, and (b) a significantly higher peritoneal fluid absorption rate (KE) caused by an increased intraperitoneal hydrostatic pressure. No significant differences were found in the diffusive mass transport coefficient for small solutes (glucose, urea, sodium, and potassium) and total protein, although the dialysate over plasma concentration ratios values were higher in the high-PRV groups. The sodium removal was significantly lower in the PRV groups as compared with the control group (P < 0.01). CONCLUSION: Our results suggest that a high PRV may decrease net ultrafiltration through decreasing the Qu, which is caused by a decreased dialysate osmolality, and increasing the KE caused by an increased intraperitoneal hydrostatic pressure. The high volume of PRV also decreased the solute diffusion gradient and decreased peritoneal small solute clearances, particularly for sodium. Therefore, a high PRV may compromise the efficiency of dialysis with a glucose solution.     

Dialysis solution containing hyaluronan: effect on peritoneal permeability and inflammation in rats

BACKGROUND: Hyaluronan (HA), a high molecular weight mucopolysaccharide found in interstitial tissues and fluid, is lost from the peritoneal cavity during peritoneal dialysis. In order to determine the role of HA in peritoneal function, we investigated the effects of exogenous HA on peritoneal permeability, markers of intraperitoneal inflammation, and peritoneal morphology in rats exposed to peritoneal dialysis solution for four weeks. METHODS: Wistar rats were infused intraperitoneally, twice daily, with conventional, hypertonic dialysis solution (Dianeal 3.86%; control) or Dianeal solution containing 10 mg/dL of high molecular weight HA. Peritoneal permeabilities and clearances of solutes and protein were determined using a modified peritoneal permeability test (peritoneal equilibration test) at the beginning and the end of the treatment. Peritoneal volume and ultrafiltration were determined using a macromolecular marker and by gravimetric methods. Peritoneal inflammation was determined by cell counts and differential and by the measurement of cytokine concentrations in the dialysate effluent. Peritoneal thickness and HA content were determined in liver and mesentery biopsies taken at the end of the experiment. RESULTS: After four weeks of exposure to the dialysis solution, transperitoneal protein equilibration was significantly lower in HA-treated rats compared with rats treated with Dianeal alone (46% lower for albumin, P < 0.003; 33% lower for total protein, P < 0.001). The total drained volume after a four hour dwell was 29% higher in the HA group compared with the control (P < 0.001), yielding a positive net ultrafiltration in the HA group versus a negative net ultrafiltration in controls. Peritoneal clearances of urea and creatinine tended to be elevated in HA-treated rats, while clearances of total protein and albumin tended to be lower. Dialysate effluent from rats exposed to HA contained a lower percentage of neutrophils (8.8 +/- 22.8 +/- 9.5%, P < 0.01) and lower levels of the cytokines, tumor necrosis factor-alpha (11.2 +/- 14.7 vs. 42.3 +/- 35.3 pg/mL, P < 0.05) and monocyte chemoattractant protein-1 MCP-1 (72.0 +/- 86.5 vs. 402.4 +/- 258.3 pg/mL, P < 0.02), compared with rats treated with Dianeal alone. The thickness of the peritoneal interstitium showed a similar increase in both groups, but mesenteric tissue from the HA group contained more HA (48%, P < 0.01) than tissue from control animals. CONCLUSIONS: The addition of HA to peritoneal dialysis solution decreases protein permeability, increases ultrafiltration, and decreases cytokine levels and the proportion of peritoneal neutrophils in dialysate from rats exposed to hypertonic dialysis solution. These results suggest that exogenous HA may help to protect the peritoneal membrane during exposure to dialysis solutions. These benefits, if sustained in the clinical setting, could lead to improvements in the therapy of peritoneal dialysis.     

Dialysate as food: combined amino acid and glucose dialysate improves protein anabolism in renal failure patients on automated peritoneal dialysis

Protein-energy malnutrition as a result of anorexia frequently occurs in dialysis patients. In patients who are on peritoneal dialysis (PD), dialysate that contains amino acids (AA) improves protein anabolism when combined with a sufficient oral intake of calories. It was investigated whether protein anabolism can be obtained with a mixture of AA plus glucose (G) as a source of proteins and calories during nocturnal automated PD (APD). A random-order cross-over study was performed in eight APD patients to compare in two periods of 7 d each AA plus G dialysate obtained by cycler-assisted mixing of one bag of 2.5 L of AA (Nutrineal 1.1%, 27 g of AA) and four bags of 2.5 L of G (Physioneal 1.36 to 3.86%) versus G as control dialysate. Whole-body protein turnover was determined using a primed continuous infusion of L-[1-13C]leucine, and 24-h nitrogen balance studies were performed. During AA plus G dialysis, when compared with control, rates of protein synthesis were 1.20 +/- 0.4 and 1.10 +/- 0.2 micromol/kg per min leucine (mean +/- SD), respectively (NS), and protein breakdown rates were 1.60 +/- 0.5 and 1.72 +/- 0.3 micromol/kg per min (NS). Net protein balance (protein synthesis minus protein breakdown) increased on AA plus G in all patients (mean 0.21 +/- 0.12 micromol leucine/kg per min; P < 0.001). The 24-h nitrogen balance changed by 0.96 +/- 1.21 g/d, from -0.60 +/- 2.38 to 0.35 +/- 3.25 g/d (P = 0.061, NS), improving in six patients. In conclusion, APD with AA plus G dialysate improves protein kinetics. This dialysis procedure may improve the nutritional status in malnourished PD patients.     

Effect of amino acid based dialysis solution on peritoneal permeability and prostanoid generation in patients undergoing continuous ambulatory peritoneal dialysis.

The acute effect of amino acid based dialysis solution on peritoneal kinetics of amino acids and plasma proteins in comparison to conventional glucose-based dialysate was studied in 9 patients with end-stage renal failure on continuous ambulatory peritoneal dialysis. Instillation of 2.6% amino acid solution resulted in raised plasma concentrations of all essential amino acids included in the dialysis fluid (p less than 0.005). The amino acid solution induced an augmented leakage of plasma proteins into the dialysate at all dwell times investigated (1-8 h). After a dwell time at 8 h, the dialysate total protein increased from 2.62 +/- 0.45 g with glucose dialysate to 3.85 +/- 0.42 g with amino acid solution (p less than 0.05). Corresponding results were obtained for beta 2-microglobulin, albumin, transferrin, IgG, and for the non-essential amino acids alanine, citrulline, and glutamine (p less than 0.025) not included in the initial amino acid composition of the dialysis fluid. During the use of amino acid based dialysis fluid, the effluent prostaglandin E2 concentration increased by more than 80% in comparison to glucose dialysate (p less than 0.025). The augmented loss of proteins induced by the amino acid solution was positively correlated with increased dialysate prostaglandin E2 (r = 0.8894; p less than 0.001). Peritoneal ultrafiltration was not affected by the use of amino acid based dialysate fluid. The present results indicate that amino acid based dialysis fluid enhances the peritoneal permeability for plasma proteins and amino acids, probably mediated by locally generated prostanoids.     

Reduction of perlecan synthesis and induction of TGF-beta1 in human peritoneal mesothelial cells due to high dialysate glucose concentration: implication in peritoneal dialysis

Prolonged exposure of the peritoneal mesothelium to high dialysate glucose concentrations reduces anionic sites that are critical to its selective permeability, thereby impairing the peritoneal transport properties in patients on long-term peritoneal dialysis (PD). Perlecan, an anionic heparan sulfate proteoglycan, is pivotal to the selective permeability of basement membranes, and high glucose concentrations modulate its synthesis in mesangial cells. The effect of glucose on perlecan expression in the peritoneal mesothelium has not been established. We investigated perlecan expression in peritoneal biopsies from patients on PD, and the effect of high glucose concentrations on perlecan synthesis in cultured human peritoneal mesothelial cells (HPMC). Peritoneal biopsies from PD patients showed reduced perlecan expression compared with controls. Exposure of HPMC to high glucose concentrations resulted in a dose-dependent reduction in the synthesis of perlecan polypeptide and its deposition into the extracellular matrix. These effects were mediated in part through the induction of TGF-beta1. Characterization studies showed that perlecan synthesized by HPMC contained solely heparan sulfate glycosaminoglycan (HS GAG) chains, and [(35)S]-incorporation studies demonstrated progressive reduction of their de novo synthesis with increasing glucose concentrations (68142 +/- 3658, 48147 +/- 2517, 31468 +/- 5781, and 25575 +/- 3621 cpm/ micro g cellular protein for 5 mM, 30 mM, 75 mM, and 120 mM D-glucose, respectively; P < 0.001 for 5 mM versus 30 mM D-glucose, and P < 0.0001 for 5 mM versus 75 mM or 120 mM D-glucose). Both the length and the charge density of the HS GAG chains remained unchanged. Reduction of peritoneal perlecan expression in long-term PD was attributed to high dialysate glucose concentrations, which induced TGF-beta1 and reduced perlecan synthesis in HPMC. Since perlecan can sequester growth factors, thereby modulating cell migration and differentiation perturbation of peritoneal perlecan expression contributes to the structural and functional changes of the peritoneum in long-term PD.     

Nocturnal ultrafiltration profiles in patients on APD: impact on fluid and solute transport

In order to prevent morbidity and mortality in peritoneal dialysis (PD), sodium and water balance as well as a minimal level of small-solute clearances are needed. The impact of three nocturnal peritoneal ultrafiltration (UF) profiles on UF and small solute clearance in patients on automated PD (APD) was studied: constant glucose concentration of 1.36% (flat) or modifying the glucose concentration of the heater bag (descendant: 3.86-1.36%; ascendant: 1.36-3.86%). Sixty-two patients were enrolled in the study and received each profile within a four-month period, thus serving as their own controls. UF was lower with the flat profile (367+/-420ml; P<0.01), but no difference was seen between the two higher glucose concentration profiles. Peritoneal Kt/V (pKt/V) and peritoneal creatinine clearance (CrpC) showed statistically higher values from the descendant vs ascendant vs flat profiles (pKt/V: 1.54+/-0.30 vs 1.45+/-0.30 vs 1.38+/-0.27, and CrpC: 36.9+/-7.9 vs 33.5+/-7.48 vs 29.92+/-7.5 mlmin(-1)). Multivariate analysis showed statistical significance for the following: in the intrasubject comparisons, the profile for pKt/V (F=9.109, P<0.001) and CrpC (F=11.697, P<0.001), and in the intersubjects comparisons, the effects of both gender (F=14.334, P<0.01) for pKt/V and peritoneal permeability for both parameters (pKt/V: F=4.37, P<0.05; CrpC: F=11.697, P<0.001). In conclusion, the application of ascendant and descendant UF profiles in automated PD is feasible and results in better UF and small solute clearances, thus preventing inadequate dialysis and volume overload..     

The effects of Panax notoginseng saponins on the cytokines and peritoneal function in rats with peritoneal fibrosis

Abstract

Background: Due to the long-term and chronic exposure to the peritoneal dialysis fluid, patients could develop peritoneal fibrosis and ultrafiltration failure which compromises treatment efficacy and outcome, and fibrosis is the major cause of peritoneal dialysis (PD) withdraw among patients. Methods: Twenty-one male WISTAR rats were randomly assigned to three groups, namely saline group, standard peritoneal dialysis fluid (PDF) group, and panax notoginseng saponins (PNS) group. Peritoneal fibrosis was induced by daily injection of PDF for 4 weeks. After execution, multiple histological techniques including HE and Masson's trichrome staining and transmission electron microscopy (TEM) were applied to observe the pathological changes and concentrations of multiple cytokines may involve in the process of fibrosis were determined by enzyme-linked immune sorbent assay (ELISA). Biochemistry parameters were determined by automated chemistry analyzer. Results: PNS can significantly inhibit the expression of transforming growth factor beta (TGF-β1), connective tissue growth factor (CTGF), and monocyte chemoattractant protein (MCP-1) in the peritoneum of rats. Furthermore, pathological damages, including extracellular matrix deposition, vascularization, and fibroblast, were ameliorated in PNS group when being compared with standard PDF group. Peritoneal functions were improved by regular PNS treatment with significantly elevated ultrafiltration. Conclusion: PNS is capable of improving peritoneal function in subjects with PDF exposure and can possibly applied in patients with PD after further verification.     

Better correction of metabolic acidosis, blood pressure control, and phagocytosis with bicarbonate compared to lactate solution in acute peritoneal dialysis

Lactate solution has been the standard dialysate fluid for a long time. However, it tends to convert back into lactic acid in poor tissue-perfusion states. The aim of this study was to evaluate the efficacy of magnesium (Mg)- and calcium (Ca)-free bicarbonate solution compared with lactate solution in acute peritoneal dialysis (PD). Renal failure patients who were indicated for dialysis and needed acute PD were classified as shock and nonshock groups, and then were randomized to receive either bicarbonate or lactate solution. Twenty patients were enrolled in this study (5 in each subgroup). In the shock group, there were more rapid improvements and significantly higher levels of blood pH (7.40 +/- 0.04 versus 7.28 +/- 0.05, p < 0.05), serum bicarbonate (23.30 +/- 1.46 versus 18.37 +/- 1.25 mmol/L, p < 0.05), systolic pressure (106.80 +/- 3.68 versus 97.44 +/- 3.94 mm Hg, p < 0.05), mean arterial pressure (80.72 +/- 2.01 versus 73.28 +/- 2.41 mm Hg, p < 0.05), percentages of phagocytosis of circulating leukocytes (65.85% +/- 2.22 versus 52.12% +/- 2.71, p < 0.05), and percentages of positive nitroblue tetrazolium (NBT) reduction test without and with stimulation (14.43 +/- 1.93 versus 9.43 +/- 2.12, p < 0.05 and 65.08 +/- 6.80 versus 50.23 +/- 4.21, p < 0.05, respectively) in the bicarbonate subgroup compared with the lactate subgroup. In the nonshock group, blood pH, serum bicarbonate, and phagocytosis assays in both subgroups were comparable. Lactic acidosis was more rapidly recovered and was significantly lower with bicarbonate solution for both shock and nonshock groups (3.63 +/- 0.37 versus 5.21 +/- 0.30 mmol/L, p < 0.05 and 2.92 +/- 0.40 versus 3.44 +/- 0.34 mmol/L, p < 0.05, respectively). Peritoneal urea and creatinine clearances in both subgroups were comparable for both shock and nonshock groups. There was no peritonitis observed during the study. Serum Mg and Ca levels in the bicarbonate subgroup were significantly lower, but no clinical and electrocardiographic abnormality were observed. We concluded that Mg- and Ca-free bicarbonate solution could be safely used and had better outcomes in correction of metabolic acidosis, blood pressure control, and nonspecific systemic host defense with comparable efficacy when compared to lactate solution. It should be the dialysate of choice for acute PD especially in the poor tissue-perfusion states such as shock, lactic acidosis, and multiple organ failure.     

Peritoneal ultrafiltration and fluid reabsorption during peritoneal dialysis

Peritoneal ultrafiltration and fluid reabsorption characteristics for 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were investigated in single dwell studies of 6 h duration with 21 of 3.86% glucose dialysis fluid. Dialysate volumes were determined in situ using radioiodinated serum albumin (RISA) as volume marker with a correction applied for the total elimination of RISA from the peritoneal cavity. The RISA elimination rate was calculated as 2.1 +/- 0.5 ml/min. The true dialysate volume after 360 min was on average 28% less than the apparent volume calculated without correction for the elimination of RISA. The mean maximum true volume plus sampling losses was 3255 ml at 240 min, corresponding to a mean net ultrafiltration volume of 762 ml between 3 min and 240 min. The mean net fluid reabsorption rate between 240 min and 360 min was 1.2 +/- 0.7 ml/min. This study of standard dialysate volume/time curves in clinically stable CAPD patients using hypertonic dialysis fluid shows that about 90% of the total net ultrafiltration is achieved during the first 90 min of the dwell. After an extended period of dialysate isovolaemia, usually lasting as long as between 120 min and 240 min, fluid reabsorption is observed in all patients.     

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.     

Short PET in pediatric peritoneal dialysis

Peritoneal equilibration test (PET) is a common technique used in children to evaluate peritoneal membrane transport capacity and adequate the dialysis regimen. Considering that this is a laborious test, a shortened version has been proposed. Our goal was to evaluate the concordance between the 2-h (short) and 4-h (classical) PET values to determine whether the short PET could be used in the clinical setting. Eighty-one PET corresponding to 81 peritoneal dialysis patients from two pediatric nephrology centers were retrospectively analyzed. Peritoneal transport capacity was evaluated using the dialysate to plasma ratio (D/P) of creatinine and the ratio of dialysate glucose to baseline dialysate glucose (D/D(0)) at 2 and 4 h. The mean [+/- standard deviation (SD)] creatinine D/P ratio at 2 and 4 h were 0.41 +/- 0.13 and 0.66 +/- 0.17, respectively, and the mean (+/- SD) D/D(0) glucose were 0.64 +/- 0.11 and 0.39 +/- 0.12 at the same times. Applying McNemar chi(2) test to evaluate the association between the categories obtained at 2 and 4 h, we found no relationship between the 2- and 4-h PET for both D/P and D/D(0) (p > 0.05). These results suggest that the use of this abbreviated test is probably not reliable for estimating the transport capacity of the peritoneal membrane in the pediatric population.     

Correlation between peritoneal mesothelial cell cytology and peritoneal histopathology with respect to prognosis in patients on continuous ambulatory peritoneal dialysis

BACKGROUND: Sclerosing encapsulating peritonitis (SEP) is a serious complication seen in patients on long-term continuous ambulatory peritoneal dialysis (CAPD). We have previously reported that mesothelial cells in effluent dialysate significantly increased in size as the duration of CAPD progressed. In this study, we investigated the relationship between mesothelial cytology, histopathology of the peritoneum, and clinical outcomes of 34 CAPD patients. METHODS: When peritoneal dialysis catheters were inserted (n = 7) or removed (n = 27), a peritoneal biopsy was performed and results compared with mesothelial cytology in effluent dialysate. RESULTS: A significant positive correlation was noted between the duration of CAPD and the surface area of peritoneal mesothelial cells (r = 0.721, p < 0.0001). The surface area of mesothelial cells in peritoneal sclerosis (n = 9; 584 +/- 97 microm(2)) was significantly greater than in peritoneal fibrosis (n = 14; 389 +/- 26 microm(2), p < 0.05), pathologic acute peritonitis (n = 3; 223 +/- 10 microm(2), p < 0.005), and normal peritoneum (n = 7; 247 +/- 12 microm(2), p < 0.001). The surface area in sclerosing peritonitis (n = 1; 1,200 microm(2)) was greater than that of all the others. Giant cells were found in the 1 case with sclerosing peritonitis and in 3 of 9 cases with peritoneal sclerosis, although they were found in only 1 of 14 patients with peritoneal fibrosis and in none of those with pathologic acute peritonitis or normal peritoneum. As the surface area of mesothelial cells increased to more than 400 microm(2) and giant cells appeared in the effluent, the frequency of peritoneal sclerosis and/or clinical SEP increased. CONCLUSION: An increase in the mesothelial cell surface area and the emergence of giant cells in the effluent indicate advanced peritoneal histopathology, and may be useful indicators to determine appropriate timing of discontinuation of CAPD to prevent the development of SEP.     

Endothelial injury in peritoneal dialysis patients with ultrafiltration failure

To evaluate endothelial injury in peritoneal dialysis patients with ultrafiltration failure (UFF), we performed a modified peritoneal equilibration test utilizing 3.86% glucose in 41 patients who had been on peritoneal dialysis for longer than 4 years. Twelve patients whose net ultrafiltrate was less than 400 mL during a 4-hour exchange were assigned to the UFF group and another 29 patients to the control group. The blood levels of vWF, a marker of endothelial injury, albumin, and lipid profile were measured. The number of antihypertensive medications and amount of 3.86% solution used were higher in the UFF group than those used in the control group (p < 0.05, p < 0.001, respectively). The patients in the UFF group had a significantly higher vWF level than those in the control group (164.8 +/- 23.1% vs. 144.5 +/- 22.4%, p < 0.05). These results showed that peritoneal dialysis patients with ultrafiltration failure had more severe endothelial injury than those without.     

Peritoneal transport characteristics with glucose polymer-based dialysis fluid in children

Scarce data are available on the use of glucose polymer-based dialysate in children. The effects of glucose polymer-based dialysate on peritoneal fluid kinetics and solute transport were studied in pediatric patients who were on chronic peritoneal dialysis, and a comparison was made with previously published results in adult patients. In nine children, two peritoneal equilibration tests were performed using 3.86% glucose and 7.5% icodextrin as a test solution. Dextran 70 was added as a volume marker to calculate fluid kinetics. Serum and dialysate samples were taken for determination of urea, creatinine, and sodium. After calculation of the initial transcapillary ultrafiltration (TCUF) rate, it was possible to calculate the contribution of aquaporin-mediated (AQP-mediated) water transport to ultrafiltration for icodextrin and 3.86% glucose and the part of L(p)S (the product of the peritoneal surface area and the hydraulic permeability) caused by AQP. In children, the transport parameters were similar for the two solutions, except for TCUF, which was lower for icodextrin (0.9 ml/min per 1.73 m(2)) as compared with 3.86% glucose (4 ml/min per 1.73 m(2)). Transport parameters were similar in children and adults for glucose, but with icodextrin, TCUF and marker clearance were significantly lower in children. AQP-mediated water flow was 83 versus 50% with glucose (child versus adult; P < 0.01) and 18 versus 7% with icodextrin (P < 0.01). Data indicate that transport parameters in children using icodextrin are similar to glucose except for TCUF. Differences are explained by the absence of crystalloid osmosis and that TCUF was determined after a 4-h dwell. Comparison of transport parameters and peritoneal membrane characteristics between children and adults reveal that there seem to be differences in the amount and functionality of AQP. However, there are no differences in clinical efficacy of this transport pathway because the absolute flow through the AQP is identical in both groups using 3.86% glucose.     

肾疏宁抑制腹膜透析腹膜纤维化大鼠基质及新生血管的实验研究

目的:观察中药肾疏宁对腹膜纤维化大鼠腹膜功能、腹膜组织基质积聚、新生血管、结缔组织生长因子(CT-GF)、血管内皮生长因子(VEGF)、肝细胞生长因子(HGF)及骨形态蛋白-7(BMP-7)表达的影响。方法:腹膜透析液+阿霉素注射法诱发SD大鼠腹膜透析腹膜纤维化模型,依体重随机分为4组,1.5%腹膜透析液模型组、4.25%腹膜透析液模型组、1.5%腹膜透析液+肾疏宁干预组及4.25%腹膜透析液+肾疏宁干预组,每组各15只,另设空白对照组(对照组,15只)。1.5%腹膜透析液+肾疏宁干预组及4.25%腹膜透析液+肾疏宁干预组予肾疏宁(按43.93g.kg-1.d-1)灌胃,对照组和模型组予等量生理盐水灌胃。检测腹透液葡萄糖浓度,计算超滤量(UF)及葡萄糖转运量(MGT)。观察腹膜病理形态学改变,分析腹膜厚度、腹膜血管计数、腹膜纤维连接蛋白(FN)及CTGF、VEGF、HGF、BMP-7表达。结果:治疗第6周末,1.5%腹膜透析液+肾疏宁干预组及4.25%腹膜透析液+肾疏宁干预组腹膜透析腹膜纤维化大鼠超滤量(-3.26±14.17)ml及(-2.04±10.74)ml、葡萄糖转运量(18.12±0.81)mmol/kg及(16.14±1.20)mmol/kg、腹膜厚度(74.68±15.33)μm及(211.75±58.23)μm、腹膜血管计数(8.21±2.66)个/mm2及(13.70±4.71)个/mm2、FN(152.47±36.94)%及(231.49±53.49)%、CTGF(708.67±127.22)%及(791.20±126.37)%、VEGF(0.42±0.08)%及(0.50±0.09)%、HGF(245.71±24.38)%及(222.05±23.43)%、BMP-7(351.27±31.99)%及(284.43±26.82)%,与同浓度透析液组比较,差异有统计学意义(P<0.05,P<0.01)。结论:肾疏宁可能通过调控CTGF、VEGF、HGF、BMP-7表达,阻抑基质过度积聚及新生血管生成,进而延缓腹膜透析大鼠腹膜纤维化进展。     

Effect of peritonitis on insulin and glucose absorption during peritoneal dialysis in diabetic rats

The intraperitoneal route is frequently used for the administration of insulin in diabetic continuous ambulatory peritoneal dialysis patients. However, there is conflicting evidence as to whether the dosage of intraperitoneal insulin should be increased or decreased during peritonitis in these patients. Glucose and insulin absorption and glycaemic control were evaluated in 2-hour exchanges using 15 ml of 2.5% dextrose dialysis solution in diabetic rats with (group 1) and without (group 2) peritonitis. Fasting blood glucose values at the beginning of the study exchanges were mean +/- SD 17.9 +/- 3.3 mmol/l in group 1 and 18.2 +/- 3.5 mmol/l in group 2. Even though group 1 had a higher percentage absorption of dialysate glucose (65 +/- 19 vs. 47 +/- 7%; p less than 0.05) and higher percentage absorption of dialysate insulin (49 +/- 12 vs. 44 +/- 14%; p less than 0.1), the hypoglycaemic response to the standard intraperitoneal dose of insulin was similar in each group. Plasma C peptide levels remained very low in both groups, thus excluding significant endogenous release of insulin. These data indicate that peritonitis per se does not change intraperitoneal insulin requirements during standardized peritoneal dialysis exchanges in diabetic rats. Insulin requirements may also be unaltered during peritonitis in diabetic continuous ambulatory peritoneal dialysis patients, provided that dialysate glucose load and oral carbohydrate intake are kept constant.