Comparison of Longitudinal Membrane Function in Peritoneal Dialysis Patients According to Dialysis Fluid Biocompatibility.

INTRODUCTION: Preservation of peritoneal function is essential in long-term peritoneal dialysis. Biocompatible dialysis solutions might prevent or postpone the membrane alteration resulting in ultrafiltration failure and consecutive morbidity and mortality. METHODS: We conducted an observational cohort study in which we made a longitudinal comparison between the course of peritoneal solute and fluid transport during treatment with conventional and biocompatible solutions. Therefore, prospectively collected peritoneal transport data from the yearly standard peritoneal permeability analysis were analyzed in 251 incident patients treated between 1994 and censoring in 2016. Fluid transport included small pore and free water transport. Solute transport was assessed by creatinine mass transfer area coefficient and glucose absorption. Linear mixed models including change point analyses were performed. Interaction with peritonitis was examined. RESULTS: One hundred thirty-five patients received conventional and 116 biocompatible solutions. Sixty-seven percent (conventional) and 64% (biocompatible) of these underwent minimally three transport measurements. Initially, biocompatible fluids showed higher small solute transport and lower ultrafiltration than conventional fluids up to 3 years. Thereafter, conventional fluids showed an increase in small solute transport (+2.7 ml/min per year; 95% confidence interval [CI]: 0.9 to 4.5) and a decrease of free water transport (-28.0 ml/min per year; 95% CI: -60.4 to 4.4). These were minor or absent in biocompatible treatment. Peritonitis induced a decrease of transcapillary ultrafiltration after 2 years on dialysis with conventional solutions (-291 ml/min per year; 95% CI: -550 to -32) while this was absent in biocompatible treatment. CONCLUSION: Despite a higher initial solute transport with biocompatible solutions, these have less influence on functional long-term peritoneal alterations than conventional solutions.

Management of encapsulating peritoneal sclerosis: a guideline on optimal and uniform treatment.

Encapsulating peritoneal sclerosis (EPS) represents a rare complication of long-term peritoneal dialysis (PD). It is characterised by diffuse peritoneal membrane fibrosis, progressive intestinal encapsulation and the clinical spectrum of intestinal obstruction. The pathogenesis is as yet not well understood but includes inflammation, angiogenesis and fibrosis. The current diagnosis of EPS lacks specificity and relies on clinical, radiographic or macroscopic evaluation. There is no general agreement on managing EPS although accumulating clinical data suggest drug treatment (steroids, tamoxifen), surgery (enterolysis) or a combination of both. Here, we provide a short overview on the current knowledge of EPS, with a focus on treatment. Moreover, we present a diagnostic and a therapeutic algorithm for EPS based on the best available published data and our combined experience.

Effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with chronic kidney disease.

Since about three decades, inhibitors of the renin-angiotensin system have been available in clinical practice. Although angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) were primarily aimed at treatment of hypertension and heart failure, more of their positive effects were discovered later on. Patients with chronic kidney disease were recognised to profit the most from treatment with these agents; however some blind spots are still present. Patients with advanced renal failure are almost always excluded from the trials; patients with end-stage renal disease form the least studied population of all and outcomes of treatment with ACEi/ARB are still uncertain in these cohorts. The aim of this review is to summarise and update the evidence about effects of AII inhibitors in patients with chronic kidney disease with the specific emphasis on patients treated with dialysis. Lately a novel indication for ACEi/ARB administration, especially for peritoneal dialysis patients, has been proposed. It is based on the capacity of these drugs to inhibit the local tissue renin-angiotensin system, which results in less development of peritoneal fibrosis and a longer life for the peritoneal membrane. The most recent available data are presented in this review.

Analysis of fluid transport pathways and their determinants in peritoneal dialysis patients with ultrafiltration failure.

Ultrafiltration failure (UFF) is a serious complication of peritoneal dialysis (PD). The aim of the study was to analyze changes in water transport and their determinants in UFF patients over the time on PD. Standard peritoneal permeability analyses of 50 stable PD patients with UFF were analyzed. Fluid transport through small pores (SPT), free water transport (FWT) at 60 min, their contributions on total ultrafiltration (SPTC and FWTC), and their determinants were assessed. Patients were divided in Group I (UFF) treated for less than 24 months, Group II treated 24-60 months, and Group III treated for more than 60 months. Group I (UFF) was compared with Group I (non-UFF) matched for the duration of PD treatment and age. Transcapillary ultrafiltration (TCUF), SPT, FWT, and FWTC were significantly lower in Group III when compared to the other UFF groups. In this group also, negative relationship was present between FWT, the ultrafiltration coefficient LpA, and osmotic conductance to glucose on one hand and PD duration on the other. FWT was positively related to osmotic conductance to glucose in all groups. Group I (UFF) showed significantly higher solute transport, effective lymphatic absorption rate, lower TCUF, and lower FWT than Group I (non-UFF). The patterns of UFF in PD patients are dependent on the duration of treatment.

Amphotericin B, mercury chloride and peritoneal transport in rabbits.

BACKGROUND: The effect of glucose-induced ultrafiltration in peritoneal dialysis is dependent on the presence and function of ultrasmall transendothelial cell water channels. The mercury-sensitive aquaporin-1 was thought to represent these transcellular pores. Amphotericin B (ampho B) has been reported to increase ultrafiltration in both experimental and patient studies. The objective of this study was to investigate the hypothesis that intraperitoneal ampho B increases and mercury chloride inhibits aquaporin-1-mediated water transport in a chronic peritoneal dialysis model in the rabbit. MATERIAL AND METHODS: Eighteen female New Zealand White rabbits were included for peritoneal catheter implantation. Peritoneal transport parameters were determined in all rabbits by standard peritoneal permeability analysis (SPAR) with 3.86% glucose-based dialysis solution during a one-hour dwell prior the intervention SPARs, as a control. Ampho B (0.06 mg/kg body weight) was added to the dialysate for 3 (n = 9) or 5 consecutive days (n = 5) before investigation. Four rabbits were investigated after 3-day i.p. 0.6 mg/kg body weight ampho B. In 3 rabbits 0.06 mg/kg body weight liposomal ampho B was administered i.p. during 3 days before intervention SPAR. Fifteen rabbits were investigated during a one-hour dwell with 0.1 mM HgCl2 containing 3.86% glucose-based dialysis solution, while they were anesthetized. Three of these underwent in vivo fixation with glutaraldehyde prior to the HgCl2 SPAR to prevent toxic effects of mercury on peritoneal tissues. RESULTS: Intraperitoneal administration of ampho B did enhance the change in intraperitoneal volume during a one-hour dwell after 3-day i.p. treatment with the low dose (p < 0.02), but it did not affect peritoneal solute permeability. This was likely mediated by transcellular water channels, but not by aquaporin-1. No beneficial effects on the ultrafiltration were found with prolonged treatment or with the higher dose. Ultrafiltration decreased (8 ml/4 h to 1 ml/4 h, p < 0.03) after i.p. administration of HgCl2 with and without in vivo fixation, accompanied by a significant decrease in aquaporin-mediated water transport, estimated as the sieving of sodium (p < 0.001). Marked increases in the clearances of macromolecules were found after i.p. HgCl2 administration due to toxic effects: total protein clearance from 97 to 172 microl/min, p < 0.005, and albumin clearance from 59 to 158 microl/min, p < 0.005. These changes were less pronounced after in vivo fixation. CONCLUSION: Ampho B has likely no clinical relevance in treatment of ultrafiltration failure in PD patients. Aquaporin-mediated water transport could be inhibited and consequently ultrafiltration was reduced by i.p. administration of mercury chloride in our rabbit model.

Icodextrin degradation products in spent dialysate of CAPD patients and the rat, and its relation with dialysate osmolality.

OBJECTIVE: Peritoneal dialysis (PD) with a 7.5% icodextrin-containing dialysis solution provides prolonged ultrafiltration compared with glucose-based dialysis solutions. Colloid osmosis is the most likely mechanism, but studies in rats suggest it is caused by an increase in osmolality due to degradation of icodextrin. Therefore, human spent dialysate was analyzed with high-performance liquid chromatography (HPLC) using gel permeation size-exclusion chromatography. An increasing peak (with a low molecular weight, < 1000 Da) was observed during the dwell. The aim of this study was to quantitate breakdown products of icodextrin (which could explain this peak) and investigate whether there was a relationship with dialysate amylase concentration and dialysate osmolality. DESIGN: Long-dwell effluents (dwell time 9.15- 14.30 hours) obtained from 12 PD patients using a 7.5% icodextrin solution during the night were analyzed. The following icodextrin breakdown products were measured: maltotetraose (G4), maltotriose (G3), maltose (G2), and glucose (G1). In 6 of these patients, the sugars maltoheptaose (G7), maltohexaose (G6), and maltopentaose (G5) were also determined in both effluent and plasma. In addition, G4, G3, G2, and G1 were measured in four Wistar rats during a 6-hour dwell study. RESULTS: In the human studies, the median distribution of the sugars in the effluent was G4,6.7%; G3,16.5%; G2, 23.1%; and G1, 53.5%. The osmolality in spent dialysate ranged between 288 and 326 mOsm/kg H2O. The median contribution of the sugars G2 - G4 was 5.4 mOsm/kg H2O. No correlation was present between dialysate osmolality and duration of the dwell (r= -0.04, p= 0.91); nor was there a relation between the concentration of G2 and duration of the dwell (r = 0.50, p = 0.10). No relationship was found between the amount of amylase and the concentration of G2 in the effluent (r = 0.49, p = 0.10), nor between the total concentration of the sugars G2 - G4 in the spent dialysate and dialysate osmolality (r = -0.31, p = 0.33). However, a strong correlation was seen between urea concentration and osmolality (r= 0.85, p < 0.001), and also between sodium concentration and dialysate osmolality in the spent dialysate (r = 0.92, p < 0.0001). The levels of the sugars G2, G3, and G4 in effluent were higher than in unused dialysate, but lower than or similar to plasma levels. Concentrations of the sugars G5, G6, and G7 were lower in spent dialysate than in unused dialysate, and higher than in plasma. In the rat study, dialysate osmolality increased with the duration of the dwell. A clear relationship was present between osmolality and concentration of the sugars G2 - G4 in the effluent. The median amount of amylase in the effluent was 1252 U/L. CONCLUSION: A 7.5% icodextrin-based dialysis solution used during the long exchange caused only a slight increase in dialysate osmolality in humans. The osmolality at the end of the dwell in the human situation was dependent mainly on concentrations of the small solutes urea and sodium in the effluent. The contribution of icodextrin degradation products was marginal. In the rat, however, a clear relationship was present between osmolality and icodextrin degradation products in spent dialysate, explaining the increased dialysate osmolality at the end of the dwell. The difference between the two species can be explained by the very high amylase concentrations in the rat, leading to a rapid degradation of icodextrin. The rat is therefore not suitable to study peritoneal fluid kinetics using icodextrin as an osmotic agent.

Ultrastructure of basement membranes of peritoneal capillaries in a chronic peritoneal infusion model in the rat.

BACKGROUND: Long-term peritoneal dialysis with glucose- based dialysis solutions has been associated with diabetiform alterations of peritoneal tissue. A peritoneal infusion model in the rat was developed to study the effect of chronic infusion of a glucose-based dialysis solution and an isotonic non-glucose solution on the ultrastructure of the basement membranes of peritoneal capillaries. The effect of ageing was also studied in an untreated control group. METHODS: A vascular access port (Rat-o-Port) with attached peritoneal catheter was implanted subcutaneously in the neck of nine male Wistar rats. The rats were divided randomly into three groups: the glucose group (n = 3) was infused daily for 20 weeks with 60 ml/kg body weight 3.86% glucose solution. A control group (n = 2) was infused daily for 20 weeks with 60 ml/kg body weight Ringer's lactate. The untreated control group (n = 4) was studied at the onset of the experiment and after 20 weeks. Omental tissue was obtained from each rat at the end of the experimental period for ultrastructural examination. RESULTS: Extensive lamination of basement membranes of omental capillaries was found in the glucose group. This was in contrast to the untreated control group where clear, single basement membranes were seen at the onset of the experiment and after 20 weeks. These latter findings were similar to those in the Ringer's lactate group. CONCLUSIONS: The chronic infusion model in the rat is suitable for the investigation of the effects on the ultrastructure of peritoneal capillaries of chronic exposure to dialysis fluids. The duplications of basement membranes of omental capillaries found in the glucose group show a striking resemblance to those found in long-term peritoneal dialysis patients. This suggests a role for glucose in the development of peritoneal ultrastructural alterations found in long-term peritoneal dialysis.

Nitric oxide-related experiments on peritoneal solute transport in the rabbit.

BACKGROUND: It is unclear whether nitric oxide (NO) is important in regulating peritoneal transport during non-infected peritoneal dialysis. METHODS: In 13 rabbits, 250 mg/l L-arginine, a substrate for NO synthesis, was added to a 3.86% glucose dialysis solution. N:(G)-monomethyl-L-arginine (L-NMMA) 25 mg/1, an inhibitor of NO synthase, was added to the dialysate in 10 rabbits. Standard peritoneal permeability analyses in rabbits were used to analyse the effects of these interventions on solute transport during 1-h dwells. The addition of 4.5 mg/l nitroprusside to the dialysate in five rabbits was used for validation of this model. RESULTS: Nitroprusside caused an 86% (48-233%) increase in albumin clearance, which is similar to the nitroprusside-induced increase found in humans (70%). Contrary to human studies, no effect was found on the mass transfer area coefficient (MTAC) of urea and creatinine, or on glucose absorption. L-Arginine did not affect either the MTAC of urea and creatinine, or the absorption of glucose. Peritoneal albumin clearance increased 18% (-24 to 609%). This resembles the NO-mediated effects of nitroprusside. Addition of L-NMMA caused no change in the solute transport rate. CONCLUSION: The rabbit dialysis model can be used for analysing the effects of interventions on peritoneal permeability characteristics, although the rabbit peritoneal membrane is probably less sensitive to NO compared with that of humans. L-Arginine-induced effects are similar to those of nitroprusside, which suggests that these effects possibly are mediated by NO. As L-NMMA did not affect peritoneal transport, it is unlikely that NO is involved in the regulation of peritoneal permeability in rabbits.

Effect of fluid supplementation and modality on peritoneal permeability characteristics in a rat peritoneal dialysis model.

OBJECTIVE: Hemoconcentration may influence peritoneal permeability parameters in anesthetized animals without fluid supplementation. Therefore, the aim of this study was to investigate the effects of fluid supplementation on peritoneal permeability in an acute peritoneal dialysis model in anesthetized rats. DESIGN: To study the effect of fluid supplementation on peritoneal permeability characteristics, 24 anesthetized male Wistar rats were investigated in 3 groups during a 4-hour standardized peritoneal permeability analysis with a 3.86% glucose dialysis solution (SPARa). The groups included a control group with no fluid supplementation (None, n = 8), a group with continuous subcutaneous infusion of 0.9% NaCl 3 mL/hr (SC, n = 9), and a group with continuous intravenous infusion of 0.9% NaCl 3 mL/hr (IV, n = 7). Inflow, sampling, and outflow of the dialysate during the SPARa occurred via a cannula inserted intraperitoneally in the lower left quadrant of the abdomen. Blood was drawn at the end of the dwell. Baseline blood samples were obtained from six separate untreated rats. RESULTS: Plasma osmolality was significantly lower in the IV group (334+/-1.4 mOsm/kg) compared to the None group (348+/-0.7 mOsm/kg, p < 0.01), and not different from the SC group (335+/-6.4 mOsm/kg), but higher than baseline (314+/-5.3 mOsm/kg, p < 0.001). Urine production during the dwell was not different among the groups: None 10.6+/-5.3 mL; SC 8.0+/-6.0 mL; and IV 10.5+/-5.6 mL. Transcapillary ultrafiltration after 4 hours was significantly higher in the IV group (p < 0.05) compared to the other two groups. Net ultrafiltration and effective lymphatic absorption were similar in all groups. Mass transfer area coefficient of urea (MTACurea) was significantly greater in the IV group (155+/-23.2 microL/minute, p < 0.003), but not different between the None (118+/-16.2 microL/min) and SC (123+/-25.9 microL/min) groups. Correcting these for the baseline plasma concentration resulted in higher values, but the IV data remained greater than the SC and None groups (p < 0.01). The glucose absorption, albumin, and IgG clearances and the sieving of sodium were alike in all groups. CONCLUSION: It can be concluded that IV fluid supplementation is more effective in preventing dehydration than SC supplementation, and it enhanced some peritoneal permeability characteristics in anesthetized rats during a 4-hour investigation. It is therefore important to standardize fluid supplementation in experiments with anesthetized animals.

Prostaglandin inhibition by intraperitoneal indomethacin has no effect on peritoneal permeability during stable CAPD.

BACKGROUND: Prostaglandins can affect the vascular response and are locally produced in the peritoneal cavity. Prostaglandin inhibition in continuous ambulatory peritoneal dialysis (CAPD) patients during peritonitis using indomethacin intraperitoneally was found to decrease the intrinsic permeability to macromolecules. METHODS: In the present study the effects of prostaglandin inhibition were studied during stable, uninfected CAPD. Two standard peritoneal permeability analyses (1.36% glucose) were performed in 10 stable CAPD patients within 1 week with and without addition of 12.5 mg/l indomethacin. Furthermore, possible effects on the parameters of nitric oxide synthesis were determined. In five other patients a high dose of indomethacin was tested. The night before the indomethacin test, 12.5 mg/l indomethacin was added to the nightdwell and the test was performed with 25 mg/l indomethacin. RESULTS: In the normal dose indomethacin group, the dialysate concentrations of prostaglandin (PG) 6-keto-PGF1alpha and thromboxane (Tx) TxB2 were significantly lower with indomethacin (IND) compared with the control dwell (C): 6-keto-PGF1alpha median 93 (C) vs 7.5 (IND) ng/l, P=0.006 and TxB2 12.3 (C) vs 9.0 (IND) ng/l, P=0.04. The dialysate concentration of PGE2 was not different during the control dwell (68.5 ng/l) compared with the indomethacin experiment (50.3 ng/l, P=0.5). The mass transfer area coefficients (MTAC) of nitrate and cGMP, and parameters of nitric oxide synthesis, were similar during both experiments. The MTAC of creatinine and urate were not different with indomethacin: creatinine median 9.5 (C) vs 10.2 ml/min (IND), P=0.2 and urate 7.2 (C) vs 7.3 ml/min (IND), P=0.3. Only the MTAC of urea was marginally higher with indomethacin: 16.0 (C) vs 16.6 ml/min (IND), P=0.04. No differences were found in the clearances of the macromolecules beta2-microglobulin, albumin, IgG and alpha2-microglobulin. With the high indomethacin dose no inhibition of PGE2 was found: 69 (C) vs 63 ng/l(IND), not significant. Furthermore, no differences were found in the transport rates of small solutes or proteins. This indicates no effect of indomethacin on the peritoneal surface area and the size-selective permeability to macromolecules. In both groups no effect was found on the transcapillary ultrafiltration and the effective lymphatic absorption rate during the 4-h dwell. Consequently, the net ultrafiltration, the difference between these, did not change. CONCLUSIONS: The indomethacin induced inhibition of the synthesis of 6-keto-PGF1alpha and TxB2 did not lead to alterations in functional parameters of the peritoneal surface area, the intrinsic permeability to macromolecules and fluid kinetics. Therefore, these prostaglandins are not likely to be involved in the regulation of peritoneal transport during stable CAPD.

Vascular endothelial growth factor in peritoneal dialysis: a longitudinal follow-up.

In a previous study, vascular endothelial growth factor (VEGF) was found to be locally produced in the peritoneal tissue of patients undergoing peritoneal dialysis (PD) who were being treated with glucose-containing PD solutions. Locally produced VEGF (LVEGF) was positively related to the mass transfer area coefficient (MTAC) of creatinine and to glucose absorption, both of which are representative of the peritoneal vascular surface area. It was therefore hypothesized that VEGF is involved in the peritoneal neoangiogenesis found in long-term PD. The aim of the present study was to investigate the time course of peritoneal VEGF levels in PD patients treated with glucose-based PD solutions during longitudinal follow-up. We also studied the effect of the switch to glucose-free PD treatment on VEGF production. Forty standard peritoneal permeability analyses (SPAs) with 3.86% glucose-containing dialysis solution were investigated. The SPAs were performed in 10 PD patients with a median number of three SPAs per patient during a follow-up of 23 months. Duration of PD treatment at the last SPA was 74 months. All patients were initially treated with glucose-containing dialysis solutions. Four patients switched after 114 months of glucose-based PD to glucose-free PD and were followed for 7 months. A PD regimen of icodextrin, glycerol, and amino acid-based dialysis solutions was applied in these patients. Four SPAs were performed per patient in this period. To predict the VEGF dialysate-to-serum ratio (D/S), when diffusion would be the only explanation for the VEGF dialysate concentration, we calculated the power relationship between D/S ratios of serum proteins that are only transported across the peritoneum and the molecular weights of those proteins. The measured VEGF D/S ratio was higher than expected (P <.001) in each observation, pointing to local production of VEGF. LVEGF increased with duration of glucose PD, 11.7 ng/L to 23.45 ng/L (P <.03). LVEGF decreased in all 4 patients undergoing glucose-free PD, from 57.35 ng/L to 23.10 ng/L. A correlation (r = 0.83, P <.001) was found be-tween the differences in MTAC creatinine between the first and last SPA during glucose-based PD and the difference in LVEGF between these observations. A similar correlation was present between the difference in glucose absorption and the difference in LVEGF (r = 0.85, P <.001). This supports a pathogenetic role of high glucose dialysate concentrations in the development of changes in the peritoneum that are found in long-term PD. Treatment with non-glucose-based PD solutions may inhibit further development of these alterations.

Expression of cancer antigen 125 by peritoneal mesothelial cells is not influenced by duration of peritoneal dialysis.

OBJECTIVE: To investigate the presence of cancer antigen 125 (CA125) on mesothelial cells in the effluent of peritoneal dialysis (PD) patients and to analyze the effect of duration of PD on the number of mesothelial cells in peritoneal effluent, the number of CA125-positive cells, and dialysate CA125 concentration. DESIGN: A cross-sectional study in which long-dwell peritoneal effluents were investigated for mesothelial cells and CA125. SETTING: A university hospital population of chronic PD patients. PATIENTS: 33 stable PD patients who were free of peritonitis during the investigation and during the 4 weeks prior to the study. METHODS: Examination of cytospin preparations of peritoneal effluent stained with May-Grünwald Giemsa, and also with an immunocytochemical double-staining method consisting of anticalretinin (pan-mesothelial cell marker) and OC125. RESULTS: A close relationship was present between the numbers of mesothelial cells counted with the two staining methods (r= 0.998, p < 0.001). On average, 92% of mesothelial cells were positive for CA125, ranging between 75% and 100% in 80% of the patients. Correlations were found between the effluent CA125 concentration and the total number of mesothelial cells (r = 0.64, p < 0.001), and also the number of CA125-positive cells (r = 0.66, p < 0.001). A negative effect of time was seen on the effluent CA125 concentration, the total number of mesothelial cells, and the number of CA125-positive mesothelial cells. However, no effect of time was present on the percentage CA125-positive cells. CONCLUSIONS: On average, 92% of mesothelial cells in peritoneal effluent are positive for CA125. This figure is not dependent on the duration of PD. Long-term PD is associated with low dialysate CA125 concentrations, a low number of mesothelial cells, and a low number of CA125-positive mesothelial cells in effluent. These results support the hypothesis that dialysate CA125 can be used as a marker of mesothelial cell mass in stable PD patients.

Peritoneal transport characteristics with glycerol-based dialysate in peritoneal dialysis.

BACKGROUND: Glycerol is a low molecular weight solute (MW 92 D) that can be used as an osmotic agent in continuous ambulatory peritoneal dialysis (CAPD). Due to its low molecular weight, the osmotic gradient disappears rapidly. Despite the higher osmolality at the beginning of a dwell, ultrafiltration has been found to be lower for glycerol compared to glucose (MW 180 D) when equimolar concentrations are used. Previous studies have shown glycerol to be safe for long-term use, but some discrepancies have been reported in small solute transport and protein loss. OBJECTIVE: To assess permeability characteristics for a 1.4% glycerol dialysis solution compared to 1.36% glucose. DESIGN: Two standardized peritoneal permeability analyses (SPA), one using 1.4% glycerol and the other using 1.36% glucose, in random order, were performed within a span of 2 weeks in 10 stable CAPD patients. The length of the study dwell was 4 hours. Fluid kinetics and solute transport were calculated and signs of cell damage were compared for the two solutions. SETTING: Peritoneal dialysis unit in the Academic Medical Center, Amsterdam. RESULTS: Median values for the 1.4% glycerol SPA were as follows: net ultrafiltration 251 mL, which was higher than that for 1.36% glucose (12 mL, p < 0.01); transcapillary ultrafiltration rate 2.12 mL/min, which was higher than that for glucose (1.52 mL/min, p = 0.01); and effective lymphatic absorption rate 1.01 mL/min, which was not different from the glucose-based solution. Calculation of peritoneal reflection coefficients for glycerol and glucose showed lower values for glycerol compared to glucose (0.03 vs 0.04, calculated with both the convection and the diffusion models). A marked dip in dialysate-to-plasma ratio for sodium was seen in the 1.4% glycerol exchange, suggesting uncoupled water transport through water channels. Mass transfer area coefficients for urea, creatinine, and urate were similar for both solutions. Also, clearances of the macromolecules beta2-microglobulin, albumin, IgG, and alpha2-macroglobulin were not different for the two osmotic agents. The median absorption was higher for glycerol, 71% compared to 49% for glucose (p < 0.01), as could be expected from the lower molecular weight. The use of a 1.4% glycerol solution during a 4-hour dwell caused a small but significant median rise in plasma glycerol, from 0.22 mmol/L to 0.45 mmol/L (p = 0.02). Dialysate cancer antigen 125 and lactate dehydrogenase (LDH) concentrations during the dwell were not different for both solutions. CONCLUSIONS: These findings show that glycerol is an effective osmotic agent that can replace glucose in short dwells and show no acute mesothelial damage. The higher net ultrafiltration obtained with 1.4% glycerol can be explained by the higher initial net osmotic pressure gradient. This was seen especially in the first hour of the dwell. Thereafter, the osmotic gradient diminished as a result of absorption. The dip in dialysate-to-plasma ratio for sodium seen in the glycerol dwell can also be explained by this high initial osmotic pressure gradient, implying that the effect of glycerol as an osmotic agent is more dependent on intact water channels than is glucose.

Neoangiogenesis in the peritoneal membrane.

OBJECTIVE: This study reviews relevant publications on the peritoneal vasculature and tries to establish morphological-functional relationships. DESIGN: The design is a review article. RESULTS: Recent morphological studies in peritoneal dialysis (PD) patients have shown the presence of diabetiform neoangiogenesis in long-term peritoneal dialysis. The same abnormalities could be induced in rats administered a high glucose dialysis solution daily for 20 weeks. The animals showed functional abnormalities in peritoneal transport similar to those found in long-term PD patients. Evidence was obtained in patients that vascular endothelial growth factor could be involved in glucose-induced peritoneal neoangiogenesis. CONCLUSIONS: Diabetiform peritoneal neoangiogenesis is an important pathogenetic factor in ultrafiltration failure in long-term peritoneal dialysis patients.

A comparison between 1.36% and 3.86% glucose dialysis solution for the assessment of peritoneal membrane function.

OBJECTIVE: To assess peritoneal membrane function with respect to fluid transport, parameters of low molecular weight solute transport, and estimations of the function of peritoneal water channels, comparing the results from a 1.36%/1.5% glucose solution with those from a 3.86%/4.25% solution in standardized peritoneal function tests. DESIGN: The study was performed in 40 stable continuous ambulatory peritoneal dialysis (CAPD) patients [median age 50 years (range: 22-74 years); duration of CAPD 9 months (range: 2-45 months)] who underwent two standard peritoneal permeability analyses (SPAs) within 1 month. One SPA used 1.36% glucose; the other, 3.86% glucose. Mass transfer area coefficients (MTACs) and dialysate-to-plasma (D/P) ratios were compared for the two solutions. Also, two different methods of estimating aquaporin-mediated water transport were compared: the sieving of sodium (3.86% glucose) and the difference in net ultrafiltration (deltaNUF), calculated as NUF 3.86% SPA - NUF 1.36% SPA. RESULTS: Median NUF in the 1.36% glucose SPA was -46 mL (range: -582 mL to 238 mL); in the 3.86% SPA, it was 554 mL (range: -274 mL to 1126 mL). The median difference in NUF for the two SPAs was 597 mL (range: 90-1320 mL). No difference between the two solutions was seen for the MTAC of creatinine (11.4 mL/min for 1.36% vs 12.0 mL/min for 3.86%) and absorption of glucose (64% vs 65%, respectively). Also, D/P creatinine was not different: 0.77 (1.36%) and 0.78 (3.86%). However, the ratio of dialysate glucose at 240 minutes and at 0 minutes (Dt/D0) was 0.34 (1.36%) and 0.24 (3.86%), p < 0.01. Values of D/P creatinine from the two glucose solutions were strongly correlated. The intra-individual differences were small and showed a random distribution. Patient transport category was minimally influenced by the tonicity of the dialysate. The minimum D/P Na+ (3.86%) was 0.884, and it was reached after 60 minutes. After correction for Na+ diffusion, D/P Na+ decreased to 0.849 after 120 minutes. The correlation coefficient between the diffusion-corrected D/P Na+ and the deltaNUF was 0.49, p < 0.01. An inverse relationship was present between MTAC creatinine and D/P Na+ (p < 0.01) This correlation can be explained by the rapid disappearance of the osmotic gradient owing to a large vascular surface area. Such a correlation was not present between MTAC creatinine and deltaNUF. CONCLUSIONS: We conclude that a standardized 4-hour peritoneal permeability test using 3.86%/4.25% glucose is the preferred method to assess peritoneal membrane function, including aquaporin-mediated water transport. The D/P Na+ after correction for Na+ diffusion is probably more useful for the assessment of aquaporin-mediated water transport than is deltaNUF obtained with 3.86%/4.25% and 1.36%/1.5% glucose-based dialysis solutions.