Amadori albumin and advanced glycation end-product formation in peritoneal dialysis using icodextrin.

OBJECTIVE: To study the influence of peritoneal dialysis (PD) solutions on the formation of early glycated products and advanced glycation end-products (AGEs). DESIGN AND PATIENTS: The formation of both Amadori albumin and AGEs in glucose- and icodextrin-based PD fluids was analyzed in vitro and in peritoneal effluents of continuous cyclic peritoneal dialysis (CCPD) patients. RESULTS: Albumin incubated with glucose-based PD fluids showed a time- and glucose concentration-dependent formation of Amadori albumin and AGEs. Aminoguanidine completely inhibited AGE but not Amadori albumin formation. Albumin incubated in icodextrin resulted in the lowest levels of Amadori albumin and AGE. Amadori albumin levels in effluents of 24 CCPD patients (12 glucose and 12 icodextrin for their daytime dwells) were similar. Dialysate samples collected during a mass transfer area coefficient test in 16 CCPD patients (8 glucose, 8 icodextrin) showed an increase in Amadori albumin formation from baseline (p < 0.0001), without a difference between the groups. In the total group, there was a positive relationship between duration on PD and dialysate Amadori albumin concentration at 240 minutes (p = 0.03). The Amadori albumin dialysate-to-plasma (D/P) ratio at 240 minutes was 0.82+/-0.11, and its clearance amounted to 7.71+/-1.14 mL/min, while the albumin D/P ratio was 0.010+/-0.003 and its clearance was 0.089+/-0.017 mL/min. In a peritoneal biopsy of a CCPD patient, Amadori albumin was observed in the mesothelial layer and the endothelium of the peritoneum. CONCLUSIONS: Using icodextrin-based instead of glucose-based PD fluids can largely reduce the formation of Amadori albumin and AGEs. However, CCPD patients using icodextrin during daytime dwells do not have lower effluent levels of Amadori albumin and AGEs, probably due to the exposure to glucose during their nighttime exchanges. Kinetic studies suggest washout of locally produced Amadori albumin.     

Contribution of lymphatic absorption to loss of ultrafiltration and solute clearances in continuous ambulatory peritoneal dialysis.

The contribution of peritoneal cavity lymphatic absorption to ultrafiltration kinetics and solute clearances in continuous ambulatory peritoneal dialysis was evaluated in patients with normal (group 1) and high (group 2) peritoneal permeability X area during 4-h exchanges using 2 liters 2.5% dextrose dialysis solution with 30 g added albumin. Cumulative lymphatic drainage in all continuous ambulatory peritoneal dialysis (CAPD) patients averaged 358 +/- 47 ml per 4-h exchange and reduced cumulative net transcapillary ultrafiltration at the end of the exchange by 58 +/- 7.2%. The peak ultrafiltration volume was observed before osmotic equilibrium between serum and dialysate was reached and occurred when the net transcapillary ultrafiltration rate had decreased to equal the lymphatic absorption rate. Thereafter the lymphatic absorption rate exceeded the net transcapillary ultrafiltration rate, and intraperitoneal volume decreased. Extrapolated to 4 X 2 liters, 2.5% dextrose, 6-h exchanges per d, lymphatic drainage reduced potential daily net ultrafiltration by 83.2 +/- 10.2%, daily urea clearance by 16.9 +/- 1.9%, and daily creatinine clearance by 16.5 +/- 1.9%. Although lymphatic absorption did not differ between the two groups, lymphatic drainage caused a proportionately greater reduction in net ultrafiltration in group 2 (P less than 0.025), because these patients had more rapid dialysate glucose absorption (P less than 0.05) and less cumulative transcapillary ultrafiltration (P less than 0.01). These findings indicate that cumulative lymphatic drainage significantly reduces net ultrafiltration and solute clearances in CAPD and that ultrafiltration failure in CAPD occurs when daily lymphatic absorption equals or exceeds daily transcapillary ultrafiltration. Reduction of lymphatic absorption may provide a means for future improvement in the efficiency of CAPD.     

Effects of intraperitoneal hyaluronan on peritoneal fluid and solute transport in peritoneal dialysis patients.

BACKGROUND: Hyaluronan (HA) is a glycosaminoglycan found in connective tissues and tissue spaces, including the peritoneal cavity. In vivo studies in a rat model of peritoneal dialysis (PD) have shown that addition of HA to PD solution during an intraperitoneal dwell can alter peritoneal fluid transport and protect the peritoneal membrane from the effects of inflammation and repeated infusions of dialysis solution. The current study sought to evaluate the safety of intraperitoneal HA and its effect on peritoneal fluid and solute transport when administered during a dialysis dwell in humans. METHODS: 13 PD patients were enrolled in a prospective, randomized crossover study involving three dialysis treatments using the following PD solutions: (1) a commercially available PD solution (Dianeal PD-4, 1.36% glucose; Baxter Healthcare Corporation, Alliston, Ontario, Canada); (2) Dianeal PD-4 containing 0.1 g/L HA, and (3) Dianeal PD-4 containing 0.5 g/L HA. Each 6-hour dialysis exchange was separated from the other exchanges by a 2-week washout period. Radioiodinated human serum albumin (RISA) was administered with the dialysis solution to evaluate intraperitoneal volume, net ultrafiltration (UF), and fluid reabsorption. Peritoneal clearances, dialysate/plasma ratios (D/P), and mass transfer area coefficients (MTACs) were determined for sodium, urea, creatinine, albumin, and glucose. Safety was evaluated by monitoring adverse events and changes in serum chemistries. Ten patients completed all three dialysis exchanges and two additional patients completed at least one treatment exchange. RESULTS: There were no reported adverse events related to HA administration and no significant changes in serum chemistries. There were no significant differences in net UF or peritoneal volume profiles among the three treatments. Mean net UF calculated using residual volumes, estimated by RISA dilution, tended to be slightly higher during treatment with solution containing 0.1 g/L HA and 0.5 g/L HA [74 +/- 86 (SE) and 41 +/- 99 mL, respectively] compared to control treatment (-58 +/- 129 mL). Although not statistically significant, there was a trend toward decreased fluid reabsorption during treatment with HA. Solute clearances, D/P ratios, and MTACs were similar for the three treatments. Serum levels of HA were also unaffected by the two treatment solutions. CONCLUSIONS: These data support the acute safety of HA when administered intraperitoneally with the dialysis solution to PD patients. Due to the small sample size and variability in net UF and fluid reabsorption, statistically significant differences were not demonstrated for these parameters. However, a trend toward decreased fluid reabsorption was observed, suggesting that HA may act by a mechanism similar to that observed in animal studies. Further studies are necessary to evaluate whether the beneficial effects of HA observed in animal studies can be shown in humans.     

Amino-acid-based continuous ambulatory peritoneal dialysis (CAPD) fluid over twelve weeks: effects on carbohydrate and lipid metabolism

Aspects of lipid and carbohydrate metabolism were studied in 8 patients established on continuous ambulatory peritoneal dialysis (CAPD) with plasma albumin less than 35 g/L, before, during, and after substitution of 1 of the daily glucose exchanges by a commercial 1% amino acid dialysis fluid for 12 weeks. The amount of glucose absorbed from the dialysis fluid was consequently reduced by about 25%, hence total energy intake decreased by about 100 Kcal/day, but peritoneal glucose transfer kinetics were unaffected. Glucose was lost into amino acid dialysate as expected (2 g/day). Excluding 1 patient with a large rise in calorie intake, total and LDL cholesterol fell at 8 and 12 weeks (LDL cholesterol week 0, 5.26 +/- 1.13; week 8, 4.32 +/- 0.74; week 12, 4.30 +/- 1.22; mean +/- SD, p less than 0.01 for both), but returned to baseline 2 weeks after the restoration of glucose fluid (LDL 4.91 +/- 1.22, p less than 0.05 vs. week 12). Apolipoprotein B concentration also fell at 12 weeks (p less than 0.01). No changes were seen in body weight, body fat, arm muscle circumference, fasting plasma glucose, insulin, growth hormone, triglyceride, nonesterified fatty acids, or HDL cholesterol. The response of these biochemical indices to single 8-h glucose and amino acid morning exchanges at 0 and 12 weeks were studied. After 12 week's use of amino acid dialysis fluid, plasma cholesterol and apolipoprotein B were significantly lower throughout the exchange.(ABSTRACT TRUNCATED AT 250 WORDS)     

Peritoneal membrane transport and hypoalbuminemia: cause or effect?

OBJECTIVE: Peritoneal membrane transport has been associated with serum albumin and clinical outcome. We examined the relationship between serum albumin and peritoneal membrane transport status before and after the initiation of peritoneal dialysis. SETTING: Patients were followed at a tertiary-care regional nephrology program at St. Joseph's Hospital, McMaster University, Hamilton, Ontario, Canada. METHODS: Incident peritoneal dialysis patients between 1 January 1995 and 31 May 1998 were eligible if there was a peritoneal equilibration test within 180 days of starting dialysis, and a serum albumin value measured within 90 days prior to, and 20 to 70 days after initiating dialysis. MAIN OUTCOME MEASURES: Serum albumin, before and after the initiation of dialysis, and the presence of proteinuric renal disease were compared with the peritoneal equilibration test results. RESULTS: Among 67 identified patients, there were 7 high, 27 high-average, 26 low-average, and 7 low transporters and the mean serum albumin values before dialysis were 35.1, 37.4, 37.8, and 40.4 g/L, respectively (p < 0.001). Serum albumin values prior to the initiation of dialysis correlated significantly with the 4-hour D/P creatinine ratio (r = -0.251, p = 0.040). After initiation of dialysis, the correlation was stronger (r= -0.447, p< 0.001). Serum albumin prior to initiation of dialysis was lower for those with proteinuric than nonproteinuric renal disease (36.4 g/L vs 38.8 g/L, p = 0.04). The trend to lower serum albumin in high transporters was seen in patients with both proteinuric and nonproteinuric renal disease. CONCLUSION: The association between higher peritoneal membrane transport and lower serum albumin is present before initiation of dialysis in both proteinuric and nonproteinuric renal disease.The poor outcomes associated with low serum albumin and higher peritoneal membrane transport might be explained by other underlying factors. The contribution of inflammation, malnutrition, and fluid overload requires further study.     

腹膜透析患者血白蛋白的季节性变化及其相关因素分析

目的 观察腹膜透析患者血白蛋白水平的季节性变化,并对此现象的相关因素进行分析.方法 在2006年9月至2007年8月期间纳入北京大学第一医院腹膜透析中心稳定透析病例41例.随访期间每1～2月测定患者血白蛋白水平,同时记录血白蛋白的影响因素,包括饮食蛋白质摄入及透析液和尿液中的总蛋白质丢失等.以上指标均按春、夏、秋、冬取季节平均值.结果 患者年龄59.69±14.23岁,中位透析龄35.85月(6～104月).经年龄、性别、透析龄、饮食蛋白质摄入及总蛋白质丢失校正后,患者血白蛋白存在季节性变化,其中夏季最低,冬季最高,分别为35.45±0.38g/L和37.19±0.39g/L(P＜0.001).但是,患者的饮食蛋白质摄入及总蛋白质丢失未呈现季节性变化.将患者按年龄中位数分为2组,其中低龄组(年龄≤62岁)较高龄组(年龄＞ 62岁)患者血白蛋白的季节性变化趋势更明显(P＜0.05),血白蛋白最高值与最低值的差值分别为2.35g/L和1.20g/L.结论 腹膜透析患者血白蛋白的季节性变化不能用饮食蛋白质摄入及蛋白质丢失的变化来解释.年龄小于62岁的腹膜透析患者血白蛋白的季节性变化趋势更为明显.这些现象的发生机制有待进一步探讨.     

The need for using an enzymatic colorimetric assay in creatinine determination of peritoneal dialysis solutions

The fate of the peritoneal membrane on continuous ambulatory peritoneal dialysis (CAPD) is usually evaluated through the modification of its permeability to various solutes as glucose, creatinine, and urea. Therefore, the accuracy of the methods used for measurements of creatinine is of great importance. A particular problem does exist for creatinine determination as it may be influenced by the presence of glucose. We studied a new enzymatic colorimetric method for creatinine determination in peritoneal dialysis solutions which contain high dextrose concentrations. Creatinine was measured in plasma, urine, and dialysate from 18 patients on CAPD and in pure dextrose solutions, with an enzymatic test (Boehringer Mannheim) and with Jaffe's reaction on two different analyzers: Astra (Beckman) and Eris (Merck). Creatinine results were similar with both assays (Jaffe's reaction and enzymatic test) when measured in blood and urine. However the Jaffe's reaction gave higher creatinine results than the enzymatic test (p less than 0.001), when assays were performed in peritoneal dialysis solutions and in pure glucose solutions. In addition, it appeared that other components of dialysis solutions, mainly calcium chloride, influenced unpredictably the results of creatinine with the Jaffe's reaction. We conclude that specific enzymatic test is a more accurate and reliable method to evaluate creatinine kinetics through the peritoneal membrane when determined in CAPD solutions.     

Abnormal erythrocyte choline transport in patients with chronic renal failure.

1. Erythrocyte choline transport has been studied in nine patients on maintenance haemodialysis for chronic renal failure, six patients on continuous ambulatory peritoneal dialysis, 31 patients with renal transplants and in nine normal control subjects. 2. The mean maximum rate of choline influx (Vmax., measured at an extracellular choline concentration of 250 mumol/l) was 66.7 (SD 14.1) mumol h-1 l-1 cells in patients on haemodialysis, 87.8 (SD 18.5) mumol h-1 l-1 cells in patients on continuous ambulatory peritoneal dialysis and 30.5 (SD 4.9) mumol h-1 l-1 cells in control subjects. The increase in choline flux in patients on haemodialysis and patients on continuous ambulatory peritoneal dialysis compared with control subjects was highly significant (P less than 0.001). 3. Renal transplant patients showed variable values for the Vmax. of choline influx (range 17.7-71.7 mumol h-1 l-1 cells). The values showed a significant negative correlation with creatinine clearance and this correlation correctly extrapolated to the maximum choline flux in normal subjects and in patients on dialysis. 4. The kinetics of choline transport have been studied in erythrocytes of patients on haemodialysis and control subjects in 'zero-trans' conditions after depletion of intracellular choline. The mean Vmax. in these conditions was 38.4 (SD 4.6) mumol h-1 l-1 cells in patients on haemodialysis compared with 14.2 (SD 3.7) mumol h-1 l-1 cells in control subjects. The mean Km under 'zero-trans' conditions was 19.4 (SD 2.4) mumol/l in patients on haemodialysis and 7.4 (SD 1.4) mumol/l in control subjects. These differences were significant (P less than 0.001).     

腹膜血管形成对腹膜透析失超滤的影响

目的　探讨腹膜透析失超滤的患病率及有关因素。方法　比较失超滤患者和非失超滤患者在透析龄、腹膜透析平衡试验 (PET)结果、腹膜炎、外周血白蛋白 (Alb)、高糖累积量及腹膜血管变化的差异。结果　失超滤患者的透析龄、腹膜通透性、高糖累积量及腹膜毛细血管的生成均高于非失超滤患者 ,但Alb相对较低 ;腹膜炎的患病率两组之间差异无显著性。结论　尿毒症环境、葡萄糖累积量的增多可能导致腹膜毛细血管的生成、腹膜的高转运 ,与腹膜透析的失超滤有关。     

A stabilising factor for gamma-glutamyl transpeptidase in urine.

Urinary gamma-glutamyl transpeptidase (gamma-GT) has been found to be stable when stored at room temperature and 4 degrees C. Activity is lost rapidly when urine is frozen but prior dialysis will prevent this loss. Urea is the major factor responsible for the loss of activity; albumin is protective at concentrations of 6 g/l or more. A factor of 10 000-30 000 molecular weight which will prevent the loss of urinary gamma-GT activity on freezing has been found in serum and urine; it has high potency in serum and in urine from patients with chronic renal failure, but only low potency in normal urine. Its nature is unknown but it is heat stable.     

Growth factors VEGF and TGF-beta1 in peritoneal dialysis.

The morphologic alterations in the kidney and the retina that can be present in patients with diabetic microangiopathy are mediated by growth factors. Vascular endothelial growth factor (VEGF) is a mediator of neoangiogenesis in diabetic retinopathy. Transforming growth factor-beta (TGF-beta) is involved in the extracellular matrix proliferation in diabetic nephropathy. The aim of the present study was to investigate the presence of VEGF and TGF-beta1 in peritoneal effluents of patients undergoing continuous ambulatory peritoneal dialysis who are being treated with glucose-containing dialysis solutions in relation to parameters of peritoneal transport. Standard peritoneal permeability analyses with 3.86% glucose dialysate were performed in 16 stable patients undergoing peritoneal dialysis (PD) (median duration of PD 39 months, range 1 to 104 months). The power relationship that is present between dialysate/serum (D/S) ratios of serum proteins that are transported only across the peritoneal membrane and their molecular weights was used to predict the D/S ratios when diffusion would be the only explanation for the measured dialysate concentration. It was assumed that all TGF-beta1 in the circulation was bound to alpha2-macroglobulin. The D/S ratios of VEGF (P < .0005) and TGF-beta1 (P < .015) were significantly higher than expected when VEGF and TGF-beta1 would have been transported from the circulation only by diffusion. No relationship was present between the effluent concentration attributed to the local production of VEGF (LVEGF) and that of TGF-beta1 (LTGF-beta1). LVEGF correlated with the mass transfer area coefficient (MTAC) creatinine value (r = 0.69, P < .007), MTAC urate value (r = 0.60, P < .02), and glucose absorption value (r = 0.75, P < .004), all reflections of the peritoneal vascular surface area. A negative correlation was observed between the transcapillary ultrafiltration (926 mL/4 h, 394 to 1262 mL/4 h) and LVEGF (r = -0.52, P < .045). This negative tendency was also observed between the net ultrafiltration (622 mL/4 h, -43 to 938 mL/4 h) and LVEGF (r = -0.48) but did not reach significance. LVEGF and the duration of treatment did not correlate, possibly because of the relatively small number of patients. LTGF-beta1 showed no relationship with transport parameters or duration of treatment. In conclusion, we found evidence for the local production of both VEGF and TGF-beta1 in the peritoneal membrane of patients undergoing long-term peritoneal dialysis with glucose-based dialysate solutions. The analogy with VEGF in diabetic retinopathy suggests a pathogenetic role of high dialysate glucose concentrations in the development of these alterations in the peritoneal membrane.     

Leukocytes in peritoneal dialysis effluents. Danish Study Group on Peritonitis in Dialysis (DASPID)

The concentration of leukocytes and the fraction of neutrophil granulocytes are two important criteria in the diagnosis of peritonitis in continuous ambulatory peritoneal dialysis (CAPD). We have found that leukocytes are unstable in dialysis effluents, resulting in false low leukocyte concentrations if not counted immediately. At 25 degrees C the leukocyte count decreases 25%-30% in 4-6 hours. Sampling in tubes containing EDTA and storage at 4 degrees C make the leukocyte concentration stable for 6 hours, while the combination of EDTA and storage at 4 degrees C ensures stability for 24 hours. When samples are handled accordingly, concentrations as high as 2 x 10(8)/L are observed without any clinical signs of peritonitis, especially within the first months of CAPD-treatment. Thus, we suggest a leukocyte-concentration of 2 x 10(8)/L as the diagnostic limit for peritonitis. Concerning fraction of neutrophils a diagnostic limit of 0.50 still seems relevant.     

Influence of residual renal function on dietary protein and caloric intake in patients on incremental peritoneal dialysis.

OBJECTIVE: To evaluate protein and caloric intake in peritoneal dialysis (PD) patients on an incremental dialysis schedule, in an attempt to discriminate the influence of residual renal function (RRF) on these nutritional parameters. DESIGN: Prospective observational study. PATIENTS: Nine patients who had significant RRF at the beginning of PD therapy, which permitted a schedule of incremental PD (i.e., the number of peritoneal exchanges was increased as the RRF fell) in order to maintain the sum of renal and peritoneal clearance (weekly Kt/V urea) at approximately 2. METHODS: The mean adequacy parameters (urine and peritoneal Kt/V urea and creatinine clearance) along with the mean dietary energy (DEI) and protein intake (DPI) estimated by 3-day diet histories, were determined 6 and 9 months after the beginning of PD, when patients had RRF (period 1), and 6 and 9 months after the loss of RRF (period 2). The mean data obtained in both periods were compared. The best determinants for the changes in DEI and DPI after the loss of RRF were also investigated. RESULTS: Mean total Kt/V urea was very similar in both periods (2.16+/-0.32 vs 2.15+/-0.18), although creatinine clearance decreased significantly after the loss of RRF (74.41+/-12.28 L/week/1.73 m2 vs 56.78+/-11.77 L/week/1.73 m2, p = 0.0001). Absolute and normalized DPI values for actual body weight decreased after the loss of RRF (68.21+/-11.87 g/kg vs 59.27+/-13.66 g/kg, p = 0.02; and 1.17+/-0.32 g/kg/day vs 0.97+/-0.32 g/kg/day, p = 0.01). Although the energy delivered by peritoneal glucose uptake increased significantly after the loss of RRF, the mean total energy intake (DEI plus peritoneal glucose uptake) was very similar in both periods (2141+/-339 kcal/day vs 2010+/-303 kcal/day, p = 0.13). However, the mean total energy intake normalized for actual body weight decreased significantly after the loss of RRF (37.5+/-10.1 kcal/kg/day vs 32.8+/-8.9 kcal/kg/day, p = 0.02). The changes in DEI and DPI between periods 1 and 2 correlated negatively with the difference of the energy delivered by peritoneal glucose uptake (r = 0.65, p = 0.05, and r = 0.88, p = 0.001, respectively). The magnitude of DPI changes between both periods correlated significantly with the magnitude of urinary Kt/V urea changes (r = 0.77, p = 0.01). However, there was no correlation between the changes in DPI and the changes in total Kt/V urea, total or renal creatinine clearance, or the length of time on PD. CONCLUSIONS: The loss of RRF led to a reduction in dietary caloric and protein intake. The magnitude of the reduction in the DPI was strongly correlated with the increase in the energy delivered by peritoneal glucose uptake and with the decrease in the urinary Kt/V urea, but not with the total Kt/V urea.     

Discriminative impact of ultrafiltration on peritoneal protein transport.

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

Peritoneal kinetics and mesothelial markers in CCPD using icodextrin for daytime dwell for two years.

OBJECTIVE: To evaluate the safety, efficacy, and biocompatibility of icodextrin (Ico), continuous cycling peritoneal dialysis (CCPD) patients were treated for 2 years with either Ico- or glucose (Glu)-containing dialysis fluid for their daytime dwell (14 - 15 hours). Prior to entry into the study, all patients used standard Glu solutions (Dianeal, Baxter BV, Utrecht,The Netherlands). DESIGN: Open, randomized, prospective two-center study. SETTING: University hospital and teaching hospital. PATIENTS: Both established patients and patients new to CCPD were included. A life expectancy of more than 2 years, a stable clinical condition, and written informed consent were necessary before entry. Patients aged under 18 years or with peritonitis in the previous month, and women of childbearing potential unless taking adequate contraceptive precautions, were excluded. Thirty-eight patients entered the study (19 Glu, 19 Ico). MAIN OUTCOME MEASURES: Daytime dwell peritoneal effluents were collected every 3 months in combination with other study variables (clinical data, laboratory measurements, dialysis-related data, and urine collection). Peritoneal transport studies were carried out every 6 months. RESULTS: In Glu- and Ico-treated patients, peritoneal transport of low molecular weight solutes and protein clearances neither changed during follow-up nor differed between the two groups. Peritoneal membrane markers (CA125, interleukin-8, carboxyterminal propeptide of type I procollagen, and aminoterminal propeptide of type III procollagen) measured in effluents did not differ between the groups and did not change over time. All these markers showed a dialysate/plasma ratio of more than 1, suggesting local production. Residual renal function remained stable during follow-up and adverse clinical effects were not observed. CONCLUSIONS: Peritoneal membrane transport kinetics and markers remained stable in both groups over a 2-year follow-up period. Membrane markers were higher in effluents than in serum, suggesting local production. No clinical side effects were demonstrated. Icodextrin was a well-tolerated effective treatment.     

Peritoneal transport of glucose in rat.

OBJECTIVE: To evaluate the convective transport characteristics of glucose and the effect of high glucose and insulin during experimental peritoneal dialysis in rat. METHODS: Male Sprague-Dawley rats weighing 300-400 g were used in this study. Mannitol (5%) was used as osmotic agent. Glucose was added to dialysis solution to yield a concentration of 100 mg/dL (group 1) or 300 mg/dL (group 2). Mannitol solution (5%) containing the same concentration of electrolytes and lactate but without glucose was used as control (group 3). In group 2, blood sugar was maintained at approximately 300 mg/dL by continuous intravenous infusion of 25% glucose solution and 0.9% NaCl solution. A 2-hour dwell study was performed with 30 mL of test solutions. Intraperitoneal volume was calculated by volume marker (18.5 kBq of 131I-human radioiodinated serum albumin, RISA) dilution with corrections made for the elimination of RISA from the peritoneal cavity (K(E)) and sample volume. The diffusive mass transport coefficient (K(BD)) and sieving coefficient (S(BRF)) were calculated by using the Babb-Randerson-Farrell model. S was also calculated directly by using isocratic methods (S(I)).The peritoneal fluid absorption rate (K(E)) was taken into account for the calculation of S(I). RESULTS: Intraperitoneal volume was significantly higher in group 2 compared with groups 1 and 3. Peritoneal fluid absorption rate, K(E), was similar in all three groups. S(BRF) and S(I) for glucose were significantly lower in group 2 compared with groups 1 and 3. S(BRF) for glucose in group 2 was below zero and S(I) near zero. K(BD) for glucose was significantly higher in group 2 than in groups 1 and 3. Plasma and dialysate concentrations of insulin increased during the initial hour and then decreased to the baseline value in groups 1 and 3, while in group 2 it continuously increased. CONCLUSION: Significantly lower sieving coefficients for glucose in the high glucose and high insulin group suggest that transport mechanisms other than simple passive transport are involved in peritoneal glucose transport, and that high glucose per se and/or high insulin may be important factors that determine glucose transport characteristics.     

长期持续性非卧床腹膜透析患者增加透析剂量对营养及充分性的影响

目的 前瞻性观察增加透析剂量对长期持续性非卧床腹膜透析(CAPD)患者的营养及透析充分性的影响。方法 36例CAPD患者，均常规行8升／日腹膜透析，其中13例夜间留腹2升，增加腹膜透析剂量为10升／日，随访三个月，评价其营养及透析充分性。结果 13例增加透析剂量组TKt/w和TCcr均显著升高(P＜0．05)，净超滤亦增加(P＜0．05)，血浆白蛋白水平虽有下降，但未达到统计学意义。结论 增加腹膜透析剂量能显著提高TKt/v和TCcr，使透析更为充分，且增加超滤量，对腹膜透析患者的长期存活有意义，且对其营养状态短期内无影响。     

Induction of 1,2-dicarbonyl compounds, intermediates in the formation of advanced glycation end-products, during heat-sterilization of glucose-based peritoneal dialysis fluids.

OBJECTIVE: To study the presence of 1,2-dicarbonyl compounds in peritoneal dialysis (PD) fluids, their concentration in effluents with increasing dwell time, and their role in the formation of advanced glycation end-products (AGEs). MEASUREMENTS: Dicarbonyl compounds in heat- and filter-sterilized PD fluids were quantified by reverse-phase high performance liquid chromatography (HPLC) after derivatization to dimethoxyquinoxaline derivatives. Kinetics of the in vitro formation of AGEs upon incubation of 1,2-dicarbonyl compounds or PD fluids with albumin, with or without aminoguanidine, were measured by AGE fluorescence (excitation/emission wavelengths of 350 nm/430 nm). PATIENTS: AGEs and dicarbonyl compounds were measured in effluents collected from standardized 4-hour dwells from 8 continuous cycling peritoneal dialysis patients. RESULTS: In PD fluids, 3-deoxyglucosone (3-DG) has been identified as the major dicarbonyl compound formed during the process of heat sterilization. The process also formed glyoxal (GO) and methylglyoxal (MGO), with the amount of 3-DG being approximately 25-60 times higher than GO and MGO. When incubated with albumin, the identified 1,2-dicarbonyl compounds rapidly formed AGEs. The formation of AGEs was more pronounced in conventional heat-sterilized PD fluids compared with filter-sterilized PD fluids, and was completely inhibited by aminoguanidine. In effluents, the concentration of MGO, GO, and 3-DG decreased with increasing dwell time, with a concomitant increase in AGE fluorescence. CONCLUSIONS: The dicarbonyl compounds 3-DG, MGO, and GO are potent promoters of AGE formation. The presence of these and possibly other dicarbonyl compounds formed during heat sterilization of glucose-based PD fluids is, to a large extent, responsible for the in vitroAGE formation by these fluids, as evidenced by the speed of AGE formation in PD fluids and the complete inhibition by aminoguanidine. Because 3-DG, MGO, and GO are rapidly cleared from PD fluids during dialysis, these compounds may contribute to the in vivo AGE formation in PD patients.     

持续腹膜透析患者的生存率及多变量预后分析

目的分析腹膜透析患者的生存率及其独立的预后因素,观察腹膜转运特性及相关临床特点对患者生存的影响。方法选择北京协和医院肾内科随诊腹膜透析患者232例,采用Cox模型回归分析透析开始时各临床指标对生存时间的影响。结果CAPD患者1年、2年、3年及4年总体生存率分别为91.1%、77.7%、68.7%及55.8%;单因素COX模型回归分析表明：糖尿病患者、腹膜高转运状态、年龄增加、血浆白蛋白低于3.0的患者预期生存率均降低（P〈0.05）。232例患者中180（78%）位患者在开始透析的前6个月完成腹膜平衡实验（PET）,其中高转运状态与死亡显著相关（与低于平均转运患者相比,RR2.70;95% CI 1.03 to 7.05;P=0.043）。经多因素COX模型回归分析,糖尿病和年龄是尿毒症腹膜透析患者死亡的独立危险因素。糖尿病患者死亡的相对危险度为非糖尿病患者的2.96倍（95% CI 1.62 to 5.38;P〈0.0001）;年龄每增加10岁,相对危险度增加0.31（P=0.039）。结论根据透析前年龄、原发病、血清白蛋白和腹膜的转运状态可以对腹膜透析患者的预后进行初步判断。     

腹膜透析引流液离心法和大网膜消化法原代培养人腹膜间皮细胞

[目的]建立和改善两种人腹膜间皮原代细胞培养的方法.[方法]分别采用离心法从腹膜透析（PD）引流液中及胰蛋白酶-EDTA消化法从人的腹膜组织中分离培养人腹膜间皮细胞（HPMC）,并分别对两种原代培养的HPMC采用相差倒置显微镜和免疫组化染色对培养的细胞进行鉴定.[结果]①两种方法均在体外原代培养成活,在相差倒置显微镜下观察细胞均呈典型的铺路石样外观,免疫组化显示两种方法培养的HPMC胞浆角蛋白、波形蛋白表达阳性,提示为腹膜间皮细胞.②经大网膜消化法获得的HPMC可传至第四代,保持原有铺路石样外观,PD引流液离心法获得的HPMC传代后生长缓慢,长期接受PD后HPMC可呈现成纤维细胞样改变.[结论]成功应用离心法和消化法进行HPMC原代培养,有助于PD研究体外实验的开展.