Dialysate to plasma solute concentration (D/P) versus peritoneal transport parameters in CAPD

The relationship between dialysate to plasma solute equilibrationratio (D/P) and diffusive (diffusive mass transport coefficients,K_BD) as well as convective (sieving coefficient, S, and netultrafiltration) transport characteristics were studied in clinicallystable CAPD patients and in patients with loss of ultrafiltrationcapacity (UFC). Forty-one 6-h single-dwell studies with standardglucose-based dialysis fluids containing 1.36/ (n = 9), 2.27%(n = 9), and 3.86% (n = 23) anhydrous glucose were carried outin 33 clinically stable CAPD patients. Eleven patients withloss of UFC were studied with 3.86% glucose solution. Intraperitonealdialysate volumes were calculated from the dilution of the tracer(¹³¹I-albumin) with a correction applied for its eliminationfrom the peritoneal cavity. K_BD and S were estimated using thePyle-Popovich-Moncrief model with aqueous plasma concentrations.A theoretical D/P curve was derived with and without takingconvective transport and peritoneal reabsorption into account. The three different glucose solutions yielded D/P curves whichwere similar for urea and potassium. For creatinine a slowerequilibration and for glucose and sodium a faster decrease indialysate concentration were observed with more hypertonic solutions.In general, there was a strong correlation which was best at240 min between D/P (for glucose dialysate/initial dialysateconcentration, D/D_o) and K_BD for all solutes (except sodium),whereas the correlation between D/P and convective transportparameters was much weaker. K_BD for creatinine (with 3.86% glucosesolution) could be estimated (r=0.98) from aqueous D/P usingthe experimental formula: creatinine K_BD= –1.8–In(1–D_24O/P)/0.1. Patients with loss of UFC due to increaseddiffusive transport (n = 8) could be discriminated from theclinically stable patients using K_BD and D/P (or D/Do) for creatinineand glucose or D/P for sodium. However, patients with loss ofUFC associated with increased peritoneal reabsorption (n = 2)could not be identified using these parameters. Theoreticallyderived D/P curves were in excellent agreement with measuredD/P for 1.36% glucose solution and simulations were satisfactoryalso for the 2.27% and 3.86% solutions provided that the effectof convective transport was taken into account. The standardized peritoneal equilibration test (PET) as proposedby Twardowski et al. [17] seems to be appropriately designedas regards duration of the dwell and the choice of glucose andcreatinine as investigated solutes. Thus, PET can be recommendedas a sensitive routine investigation for the monitoring of normal/abnormalperitoneal transport behaviour in peritoneal dialysis patients.     

腹膜厚度与腹膜溶质转运功能的相关性

目的 探讨腹膜透析患者腹膜厚度与基线溶质转运功能的关系,分析腹膜转运功能的影响因素.方法 入选2017年1月至2019年6月福建省龙岩市第二医院肾内科收治的非糖尿病终末期肾脏病(ESRD)患者为研究对象.腹膜透析置管术前用彩色超声仪测量患者壁层腹膜厚度.腹膜透析治疗后1个月行标准腹膜平衡试验(PET)检查,以4h腹透液的矫正肌酐与2h血清肌酐的比值(D/Pcr)作为基线溶质转运指标,并按照D/Pcr评估结果分为高/高平均转运(H)组(D/Pcr≥0.65)和低/低平均转运(L)组(D/Pcr< 0.65).比较两组患者临床资料、壁层腹膜厚度和腹膜透析相关指标的差异;二元Logistic回归法分析腹膜转运功能的影响因素.结果 共纳入70例非糖尿病ESRD患者,H组患者腹膜超滤量显著低于L组;腹膜内生肌酐清除率(Ccr)和腹膜厚度显著高于L组(均P<0.05).Pearson及Spearman相关性分析结果显示,腹膜透析患者壁层腹膜厚度与溶质转运指标D/Pcr(r=0.673)、腹膜内生肌酐清除率(Ccr,r=0.261)呈正相关,与腹膜透析超滤量呈负相关(r=-0.365,均P<0.05).偏相关分析结果显示,腹膜厚度与溶质转运指标D/Pcr (r=0.539)、腹膜Ccr(r=0.338)呈正相关(均P<0.05).二元Logistic回归分析结果显示,腹膜增厚是腹膜转运功能的危险因素(OR=1.175,95%CI1.009~ 1.369,P=0.038).结论 非糖尿病腹膜透析患者壁层腹膜厚度与基线溶质转运指标呈正相关,腹膜增厚是影响腹膜转运功能的危险因素.     

Multidirectional approach to study peritoneal dialysis fluid biocompatibility in a chronic peritoneal dialysis model in the rat.

BACKGROUND: Peritoneal dialysis causes the functional and morphological changes in the peritoneum that result from the bioincompatibility of dialysis solutions. We present a model of chronic peritoneal dialysis in the rat that can be used for testing the biocompatibility of dialysis fluids. Methods and Results. Long-term exposure of the peritoneum to dialysis solutions can be performed in rats with implanted peritoneal catheters. Sampling of the dialysate allows the evaluation of intraperitoneal inflammation by examining cell differential and dialysate cytokine levels. Peritoneal permeability can be evaluated at designed time intervals with the peritoneal equilibration test (PET). At the end of dialysis, peritoneal histology is studied with light and electron microscopy. CONCLUSIONS: Such a multidirectional approach is an effective way to test biocompatibility of dialysis solutions.     

Intraperitoneal hydrostatic pressure and flow characteristics of peritoneal catheters in automated peritoneal dialysis.

BACKGROUND: In automated peritoneal dialysis (APD) one of the most important factors that influence the efficiency of the treatment is the total volume of dialysate infused per session and the dwell time. This study is aimed at examining the relationships between i.p. pressure (IPP), dialysate flow characteristics, and different dialysate fill volumes in order to optimize APD. METHODS: We studied 20 patients who received APD, with the standard fill volume (2 l, A), or individualized fill volumes based on the patient's body surface area (2.5 l/BSA/1.73 m, B) or on body weight (40 ml/kg body weight, C). The patient's tolerance to a given fill volume was evaluated by measuring IPP, and catheter flow characteristics were evaluated by an automated machine. RESULTS: IPP increased with the increase of the infused volume of dialysate (P < 0.05) and tended towards a positive relationship with the patient's body mass index (BMI: A vs IPP: R = 0.39, P = 0.0019; B vs IPP: R = 0.66, P = 0.0012; C vs IPP R = 0.55, P = 0.009). We also found a relationship between fill volume, BMI and IPP: IPP = 1.0839 + 0.53 (beta) x BMI + 0.211 (beta) x fill volume (R = 0.65; r(2) = 0.40 P < 0.01). The mean IPP with different dialysate fill volumes tended to be related to the volume of dialysate drained at the transition point (R = 0.37; P < 0.05). The pre-transition flow rate/mean IPP ratio tended towards a positive relationship with the volume of dialysate drained at the transition point (R = 0.35, P < 0.05), the transition time (R = 0.34; P < 0.05) and a negative one with the transition volume (R = -0.35, P = 0.05). CONCLUSION: It is possible to customize APD, where the tidal percentage coincides with the transition point for a given catheter and a specific initial dialysate fill volume, the tolerance of which can be measured by assessing IPP.     

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.     

Increases in peritoneal small solute transport in the first month of peritoneal dialysis predict technique survival

BACKGROUND: Peritoneal transport of small solutes generally increases during the first month of peritoneal dialysis (PD). The aim of this study was to prospectively evaluate the ability of the peritoneal equilibration test (PET), carried out 1 and 4 weeks after the commencement of PD, to predict subsequent technique survival. METHODS: Fifty consecutive patients commencing PD at the Princess Alexandra Hospital between 1 February 2001 and 31 May 2003 participated in the study. Paired 1 week and 1 month PET data were collated and correlated with subsequent technique survival. RESULTS: A significant increase was observed in the dialysate : plasma creatinine ratio at 4 h (D/P Cr) between 1 and 4 weeks after the onset of PD (0.55 +/- 0.12 vs 0.66 +/- 0.11, P <0.001). Mean death-censored technique survival was superior in patients who experienced > or =20% rise in D/P Cr during the first month of PD compared with those who did not (2.3 +/- 0.2 vs 1.6 +/- 0.2 years, P <0.05). Using a multivariate Cox proportional hazards model analysis, the significant independent predictors of death-censored technique survival were an increase in D/P Cr of greater than 20% during the first month (adjusted hazard ratio [HR] 0.20, 95% CI 0.05-0.75), the absence of diabetes mellitus, the absence of ischaemic heart disease, body mass index and baseline peritoneal creatinine clearance. CONCLUSIONS: A 20% or greater rise in D/P Cr during the first month of commencing PD is independently predictive of PD technique survival. Further investigations of the mechanisms underlying this phenomenon are warranted.     

Effect of peritoneal dialysis fluid composition on peritoneal area available for exchange in children.

BACKGROUND: Although conventional peritoneal dialysis fluids (PDFs), such as Dianeal, are non-physiological in composition, new PDFs including Physioneal have a more neutral pH, are at least partially buffered with bicarbonate and, most importantly, contain low concentrations of glucose degradation products (GDPs). METHODS: To evaluate the impact of new PDFs in childcare, we performed a comparative crossover study with Dianeal and Physioneal. We examined both intraperitoneal pressure (IPP), which partly reflects pain induction, and the total pore area available for exchange, which indicates the number of capillaries perfused in the peritoneal membrane at any given moment and therefore partly reflects peritoneal dialysis capacity. The IPP was determined after inflow of 1000 ml/m(2) body surface area (BSA) of dialysate (intraperitoneal volume; IPV). The steady-state unrestricted area over diffusion distance (A(0)/ triangle up x, in cm(2)/cm per 1.73 m(2) BSA) was calculated from the three-pore theory. Six children were enrolled in the study. On the first day, two consecutive peritoneal equilibration tests of 90 min each were performed using first Dianeal and then Physioneal. On the second study day, the procedure was repeated with the fluids given in the opposite order. RESULTS: The mean IPP normalized to IPV (ml/m(2)) was significantly higher for Dianeal (9.5 +/- 0.9 cm/1000 ml/m(2)) than for Physioneal (7.9 +/- 1.2 cm/1000 ml/m(2), P < 0.01). The mean A(0)/ triangle up x was 17 +/- 4% larger with Dianeal (36 095 +/- 2009 cm(2)/cm per 1.73 m(2)) than with Physioneal (31 780 +/- 2185 cm(2)/cm per 1.73 m(2), P < 0.001; based on 24 data pairs). CONCLUSIONS: These pilot study results suggest a higher biocompatibility for Physioneal than for Dianeal. Less inflow pain associated with Physioneal induced a lower IPP reflecting enhanced fill volume tolerance, and the lower A(0)/ triangle up x reflected less capillary recruitment. Taken together, these results suggest that the new more biocompatible PDFs will improve peritoneal dialysis therapy, although this conclusion will require verification in extended clinical trials.     

A high peritoneal large pore fluid flux causes hypoalbuminaemia and is a risk factor for death in peritoneal dialysis patients.

BACKGROUND: Hypoalbuminaemia is common in peritoneal dialysis (PD) patients and has an associated high mortality. An excess morbidity and mortality has previously been found in patients with high peritoneal transport. A high peritoneal large pore fluid flux (Jv(L)) results in increased peritoneal loss of protein that possibly contributes to patient morbidity. Alternatively, hypoalbuminaemia and high transport status could be just a marker of capillary pathology associated with atherosclerotic comorbidity. METHODS: Peritoneal dialysis capacity computer modelling of peritoneal transport, based on Rippe's three-pore model, was performed to measure Jv(L) in 155 incident PD patients 2-4 weeks after PD initiation. Patient clinical and biochemical status was determined -6, -3, -1, 1 and 6 months after PD initiation, and every 6 months thereafter. Jv(L) was redetermined in prevalent patients 2 and 4 years after PD initiation. RESULTS: Jv(L) was 0.106+/-0.056 ml/min/1.73 m(2) (median 0.094, interquartile range 0.068-0.128). It was correlated to age*** (*P<0.05; **P<0.01; ***P<0.001) (20-30 years 0.079+/-0.04; 70 years 0.121+/-0.071), but not to gender. No correlation to diabetic or preexisting renal replacement therapy was seen, but patients with atherosclerosis had higher Jv(L) (0.123+/-0.06 vs 0.100+/-0.056*) as had patients with other systemic disease (0.121+/-0.68 vs 0.100+/-0.051*). Jv(L) was positively correlated to area parameter (r = 0.41***), and negatively correlated to plasma albumin (-0.36***). Patients were divided into three equal groups: group 1, Jv(L) <0.075 ml/min/1.73 m(2); group 2, 0.075-0.11; group 3: >0.11. There was no difference between the groups in p-albumin prior to PD. Immediately after PD start, differences between the three groups appeared (1 month p-albumin: (micromol/l) group 1, 548+/-83; group 2, 533+/-86; group 3, 497+/-78**), and persisted for up to 6 years. No significant change in Jv(L) was seen at 2 and 4 years. Patients with significant albuminuria also had hypoalbuminaemia (<1 g/day: 546+/-81 mumol/l; >2 g/day: 503+/-54 micromol/l). Intermittent PD ameliorated the effect of Jv(L) on albumin losses and clearance. Mortality was increased significantly with raised Jv(L), independently of age (2 year mortality: group 1, 10%, group 3, 32%*). There was no overall effect on technique survival, but hypoalbuminaemic group 3 patients had a higher failure rate. CONCLUSION: Jv(L) is related to hypoalbuminaemia and mortality after PD initiation. A high Jv(L) seems to be a marker of preexisting vascular pathology, and to cause hypoalbuminaemia after PD initiation. It is suggested that peritoneal albumin loss can have an identical pathogenic effect as urinary albumin loss, by causing an iatrogenic "nephrotic" syndrome.     

Factors influencing peritoneal transport parameters during the first year on peritoneal dialysis: peritonitis is the main factor.

BACKGROUND: Studies on the evolution of peritoneal transport during the first year of peritoneal dialysis (PD) are scarce and their results are contradictory. The aim of the present study was to analyse the evolution of peritoneal transport and residual renal function during the first year on PD, and to determine the factors that may influence them. METHODS: We studied 249 patients on continuous ambulatory PD with glucose exchange solutions (117 men, 132 women, mean age 51.9+/-16 years) 59 of whom had diabetes (25 type I). At baseline and after 1 year, we determined the mass transfer coefficients of urea (U-MTAC) and creatinine (Cr-MTAC), net ultrafiltration and residual renal function. RESULTS: Residual renal function decreased significantly during the first year (from 3.9+/-2.8 to 2.4+/-2.2 ml/min, P<0.001). Both U-MTAC and Cr-MTAC decreased after 1 year [U-MTAC from 22.7+/-7.8 to 20.7+/-6.6 ml/min (P<0.001), Cr-MTAC from 10.5+/-5.3 to 10.1+/-4.6 ml/min (NS)]. The ultrafiltration capacity increased significantly (from 923+/-359 to 987 U 341 ml/4 h, P<0.001). The evolution of MTAC values was independent of age, sex, diabetes and amount of hypertonic glucose used. When patients were grouped according to their initial Cr-MTAC, we observed a tendency toward normalization of the parameters of peritoneal function. Patients with peritonitis (n = 88) showed a first year increase in Cr-MTAC, which was significantly higher than in patients without peritonitis (11.1+/-5 vs 9.5+/-4.2, P<0.01). Ultrafiltration decreased in patients with more than four accumulated days of peritonitis (from 1062+/-447 to 1024+/-340 ml/4 h, NS); it increased in patients without peritonitis. CONCLUSIONS: The peritoneal transport parameters tended toward normalization during the first year on PD, mainly with a decrease of small solute transport and an increase of ultrafiltration capacity. This evolution is independent of age, gender, diabetes and higher exposure to glucose in PD solutions. Peritonitis was the only independent factor that affected peritoneal function during the first year on peritoneal dialysis.     

Peritoneal thickening is not inevitable in long-term peritoneal dialysis and is associated with peritoneal transport characteristics: a two-centre sonographic study.

BACKGROUND: The peritoneum is subject to alterations in the life-long course of peritoneal dialysis (PD). Studies of the parietal peritoneum by non-invasive ultrasonography in PD patients are limited. We hypothesize that a prolonged PD duration is associated with a thicker peritoneum on ultrasonography and alterations in Doppler indexes of mesenteric vessels. METHODS: We recruited two groups of patients, 18 who had >7 years of PD and 18 who had <12 months of PD. We excluded patients with active peritonitis, history of major abdominal surgery, cirrhosis or malignancy. We measured the sonographic thickness of the parietal peritoneum and Doppler indexes of mesenteric vessels by trans-abdominal ultrasonography at two PD units in Taiwan. RESULTS: We found no significant difference between two groups of PD patients in peritoneal thickness and in Doppler indexes. However, our univariate and multivariate analysis indicated that peritoneal thickness is associated with peritoneal transport characteristics (dialysate/plasma creatinine) but not with age, duration of dialysis, body height, body weight or Doppler index. The peritoneum is significantly thicker in rapid transporters than in slow transporters (RUQ: 0.59 +/- 0.40 mm versus 0.27 +/- 0.29 mm, P = 0.01; LUQ: 0.60 +/- 0.40 mm versus 0.27 +/- 0.32 mm, P = 0.016; LQ: 1.07 +/- 0.85 mm versus 0.48 +/- 0.53 mm, P = 0.026). In addition, rapid transporters have a marginally lower Doppler resistive index of the superior mesenteric artery (0.87 +/- 0.08 versus 0.90 +/- 0.10, P = 0.028). CONCLUSIONS: Our data showed that peritoneal thickening is not inevitable in long-term PD patients. Sonographic thickness in the parietal peritoneum is associated with transport characteristics. Rapid transporters have a significantly thicker peritoneum. The Doppler index of mesenteric vessels had no association with PD duration or transport characteristics. Trans-abdominal ultrasonography is non-invasive and useful in evaluating peritoneal characteristics of PD patients.     

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

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

Longitudinal changes of solute transport in peritonitis-free peritoneal dialysis patients

BACKGROUND: The aim of this study was to evaluate the longitudinal changes in peritoneal transport in patients on long-term, peritonitis-free, continuous ambulatory peritoneal dialysis (CAPD) therapy. METHODS: Results were longitudinally recorded for the standard peritoneal equilibration test (PET) in 76 consecutive, nondiabetic, adult patients from the beginning of CAPD therapy until their first episodes of peritonitis, abdominal surgery, or any cause of drop out. The PET results were evaluated once annually using the dialysate-to-plasma ratio of creati-nine (D/PCr) and the dialysate-to-instilled dextrose ratio (D4/D0) at 4 hours after beginning dialysis. RESULTS: A total of 168 PET results were obtained. A statistically significant tendency toward decreased D/PCr and increased D4/D0 values over time for up to 3 years was found. CONCLUSIONS: This study shows a tendency toward progressive decline in small molecular transport over time in nondiabetic patients with uneventful CAPD therapy. Sequential PET follow-up cannot be overlooked in peritonitis-free CAPD patients.     

Effects of anaesthesia on fluid and solute transport in a C57BL6 mouse model of peritoneal dialysis.

BACKGROUND: Genetically modified mice show promise as animal models for studying the physiology and pathophysiology of the peritoneum during peritoneal dialysis (PD). Methods for evaluation of the functional characteristics of the mouse peritoneum have not been studied extensively, and the effects of anaesthesia on fluid and solute transport in mouse models of PD are unknown. METHODS: A single exchange of dialysis solution was performed in C57BL6 mice by injecting fluid into the peritoneal cavity using a 27-gauge needle and allowing fluid to dwell for 30, 60 or 120 min. Experiments evaluated the effect of ketamine (plus xylazine) anaesthesia on fluid and solute transport; these effects were examined in separate experiments using glucose and mannitol as the osmotic agent added to the injected dialysis solution. After euthanasia, blood was collected, the remaining dialysis solution was drained and their contents analysed for concentrations of the osmotic solute (glucose or mannitol), urea nitrogen (UN), sodium (Na) and a volume marker (fluorescein-labelled albumin) added to the initial, injected dialysis solution. Determined parameters included final volume of dialysis solution (drained plus residual fluid volume), dialysate concentration (D/D0) of glucose (or D/D0 mannitol), dialysate-to-plasma concentration ratio for (D/P) UN and D/P Na and the apparent dialysis solution volume by indicator dilution. Peritoneal permeability-area (PA) values or mass transfer-area coefficients were also calculated for the osmotic solutes. RESULTS: Final volumes of dialysis solution were higher when mice were anaesthetized with ketamine than in unanaesthetized mice, independent of whether glucose or mannitol was used as the osmotic agent. The increases in final volume were paralleled by higher dialysate concentrations (D/D0 values) and lower calculated PA values for both glucose and mannitol. When using either osmotic agent, anaesthesia also increased plasma glucose concentrations, suggesting that ketamine altered glucose metabolism. CONCLUSIONS: Ketamine anaesthesia in the mouse decreases PA values for glucose and mannitol when used as osmotic agents in PD solutions. The decrease in transperitoneal transport for these osmotic agents increases the final volume of fluid which can be obtained from the peritoneal cavity.     

Longitudinal changes in peritoneal kinetics: the effects of peritoneal dialysis and peritonitis

BACKGROUND.: Peritoneal infection and poor ultrafiltration continue to bethe major causes of treatment failure in CAPD. The combinedeffects of peritonitis and the continuous exposure to dialysisfluid remain the most likely candidates affecting the peritoneumin the long term. The purpose of this study was to observe theeffects of peritonitis and dialysis on longitudinal peritonealfunction. METHODS.: The peritoneal equilibration test (PET) was utilized to quantifylongitudinal changes in low-molecular-weight solute transfer(D/P_creat) and ultrafiltration (UF) in 233 patients treatedwith CAPD. Of these, 166 represented an unselected cohort (Group1) studied prospectively from commencing treatment for up to54 months, and 67 were selected patients (Group 2) with PETdata available at commencement of the study, having been ondialysis for a minimum of 18 months. PETs were performed either6-monthly or following peritonitis episodes. RESULTS.: Data on the short-term effect of peritonitis kinetics were pooledfor groups 1 and 2. Single, isolated episodes (n = 86) had nosignificant effect on D/P_creat or UF, whereas recurrences orclusters of infection (n = 70) caused increases in D/Pcreatand reductions in UF, the significance of which increased withthe number of episodes. There were significant correlationsbetween both changes in D/P_creat and UF with the cumulativedialysate leukocyte count, regardless of infecting organism,suggesting that intensity of peritoneal inflammation is alsoimportant. Those organisms associated with greater change inperitoneal kinetics, e.g. S. aureus, Pseudomonas, also had thehighest neutrophil counts. The longitudinal changes in peritoneal kinetics were analysedfor patients in group 1 only. There was a highly significantincrease in D/P_creat after 6 months treatment; this increasedfurther with time on treatment, reaching further significanceat 42 and 48 months. There was an associated reduction in UF.In view of the short-term effects of peritonitis on kineticsgroup 1 was further subdivided into patients who were eitherperitonitis free or only experienced isolated infections, group1a, and those that had multiple infection episodes, group 1b.Treatment drop-out, due to death or technical failure occurredat double the rate in group 1b, who also had significantly higherD/P_creat and lower UF at 1, 6, 12, 18 and 24 months of treatment.Group 1a subsequently caught up, however, indicating that peritonitisis not the only factor influencing long-term changes in peritonealkinetics. CONCLUSIONS.: These data suggest that solute transfer increases and UF declineswith time on peritoneal dialysis. This process is exacerbatedand accelerated by peritonitis, and appears to be proportionalto the degree of associated inflammation and number of infectionsin close proximity.     

The cellular contribution to effluent potassium and its relation to free water transport during peritoneal dialysis.

BACKGROUND: Aquaporin-1 (AQP-1) dysfunction is one of the valid theories for decreased free water transport (FWT) in long-term peritoneal dialysis (PD) ultrafiltration failure (UFF). We questioned whether apoptosis of peritoneal cells could be reflected in an increased release of cellular (CR) K(+) and explain AQP-1 dysfunction. If so, negative relationships between CR-K(+) and FWT would be expected. Therefore, we analysed CR-K(+) to total peritoneal K(+) removal, for possible relationships with FWT, the duration of PD, the presence of late UFF and effluent cancer antigen (CA) 125. METHODS: Standard peritoneal permeability analyses done with 3.86% glucose were investigated cross-sectionally in three extreme groups: group I: 19 patients <1 year on PD; group II: 20 patients >4 years on PD without UFF; group III: 19 patients >4 years on PD with UFF. RESULTS: Group III had the lowest values of FWT and CR-K(+) (P < 0.01). CR-K(+) had a positive correlation with FWT in groups I and II, but not in group III. These correlations were also present using much simpler methodologies: replacement of CR-K(+) by mass transfer area coefficient (MTAC)-K(+)/MTAC-creatinine ratio or dialysate over plasma (D/P)-K(+)/D/P-creatinine ratio and replacement of FWT by Na(+)-sieving. No relationship with CA125 was present. CONCLUSIONS: This study shows that other than diffusive and convectional, K(+) transport is not excluded in patients treated with conventional glucose-based PD solutions. We found evidence for release of K(+) from cells. In general, CR-K(+) was related to parameters of FWT, except for long-term patients with UFF. This suggests glucose-induced hypertonic cell shrinkage as a basic physiological phenomenon during PD. The absence of this relationship in long-term PD patients with UFF either suggests a reduction or inhibition of K(+)-channels and may be due to another mechanism than AQP-1 dysfunction. Most likely, CR-K(+) in UFF does not reflect apoptosis. However, the D/P-K(+)/D/P-creatinine ratio may be useful in detecting peritoneal changes.     

Association between interleukin-10 gene polymorphism -592 (A/C) and peritoneal transport in patients undergoing peritoneal dialysis

Aim: The aim of this analysis was to know whether these three cytokine polymorphisms, including interleukin‐6 (IL‐6; ?572 G/C), tumour necrosis factor‐α (TNF‐α; ?308 G/A), and IL‐10 (–592 A/C) have an effect on baseline peritoneal transport property and longitudinal evolution of peritoneal function. Methods: A total of 141 stable peritoneal dialysis (PD) patients with mean treatment duration of 84.4 ± 34.2 months were enrolled. We genotyped these three cytokine polymorphisms, together with clinical parameters that were included as factors affecting longitudinal change of property of peritoneal transport over the first 3 year period after commencing therapy. Results: There was no significant association between genotypes and baseline peritoneal transport property. The ?592 A/C polymorphism of IL‐10 was associated with longitudinal change of peritoneal transport. The ratio of D/P creatinine was significantly higher in patients with AA than those with CC/CA genotypes at 12 months (0.65 ± 0.11 vs 0.62 ± 0.09, P = 0.048) and 24 months (0.64 ± 0.12 vs 0.59 ± 0.09, P = 0.018). In addition, patients with increased peritoneal transport have greater frequency distribution of AA genotype and A allele. Logistic regression analysis revealed that ?592 A allele was an independent predictor for the increase in D/P creatinine over the first 12 month period (odds ratio: 2.482, P = 0.017). There was no correlation between either polymorphism of IL‐6 ?572 (G/C) or TNF‐α?308 (G/A) and longitudinal change of peritoneal function. Conclusions: Single nucleotide polymorphism of IL‐10 ?592 (A/C) was associated with longitudinal evolution of peritoneal transport rate in PD patients rather than the baseline peritoneal characteristics.     

Inhibition of Rho-kinase alleviates peritoneal fibrosis and angiogenesis in a rat model of peritoneal dialysis

Abstract

Background/Aims: The present study investigated whether Rho-kinase inhibition had a therapeutic role on the pathogenesis of peritoneal fibrosis and angiogenesis. Methods: A rat model of peritoneal dialysis was induced by a daily intraperitoneal infusion of 4.25% Dianeal. Those rats were treated with Rho-kinase inhibitor, fasudil. Immunofluorescence, Western blot and RT-PCR were used to detect the expression of TGF-β1, Collagen I, αSMA and VEGF in each group. Microvessel density (MVD) was measured by immunohistochemistry. Rho-kinase activity was determined by western immunoblotting. Results: Rho-kinase was activated in the peritoneum of the PD group, which was inhibited by fasudil. Compared with PD group, the mRNA and protein expressions of TGF-β1, αSMA and Collagen I were significantly downregulated in fasudil treatment groups in a dose-dependent manner, and the expression of VEGF and peritoneal MVD was also significantly downregulated in fasudil treatment groups in a dose-dependent manner. Conclusion: The Rho-kinase was activated in the peritoneum of the peritoneal dialysis rats, and the inhibition of Rho-kinase by fasudil can remarkably decrease peritoneal fibrosis and angiogenesis.     

In vitro buffering capacity of residual peritoneal dialysate fluid: implications for peritoneal dialysis therapy

The buffering capacity of the residual peritoneal dialysate fluid from each of 5 patients undergoing continuous ambulatory peritoneal dialysis was assessed by titrating with fresh, conventional, acidic, and lactate-containing peritoneal dialysis solutions. It was found that residual fluids had considerable buffering capacity.