Fluorodeoxyglucose positron emission tomography detects the inflammatory phase of sclerosing peritonitis.

OBJECTIVE: We studied the effectiveness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in detecting inflammation in known or suspected cases of sclerosing peritonitis in patients on peritoneal dialysis (PD). DESIGN: We undertook FDG-PET scanning in PD patients presenting with symptoms or signs suggestive of sclerosing peritonitis (SP), and in patients on long-term PD with no symptoms of SP. SETTING: The study was performed in a PD unit in a tertiary-care hospital. PATIENTS AND METHODS: Three patients with known or strongly suspected SP underwent FDG-PET scans, 1 within 3 months of presentation with symptoms and 2 who were scanned more than 9 months after presentation. One patient was scanned at an early and a late time point. Five patients who had been on PD for more than 5 years and who were asymptomatic also underwent FDG-PET scanning. Scans were interpreted by a specialist in nuclear medicine. RESULTS: The scan performed in the early stages of SP showed increased peritoneal uptake. However, three scans taken more than 9 months after presentation with suspected SP showed mild peritoneal abnormalities only. One of 5 asymptomatic long-term PD patients showed increased peritoneal uptake associated with loss of ultrafiltration and high transporter status. CONCLUSIONS: FDG-PET scanning may be a useful adjunct in the diagnosis of the acute phase of SP. More study is needed to define its role in the diagnosis of SP in asymptomatic PD patients.     

No significant differences in peritoneal fluid handling in children using PH-neutral or acidic solutions.

OBJECTIVES: Differences in peritoneal fluid handling in the acute setting can be expected if children are converted to pH-neutral dialysis solutions because conventional acidic solutions exert toxic effects on peritoneal mesothelial cells and microcirculation. Peritoneal fluid kinetics was therefore investigated with both types of solutions in a group of children. DESIGN: Peritoneal equilibration tests (PETs) were performed in 12 patients [mean age 70 months, mean time on peritoneal dialysis (PD) 18 months] using a pH-neutral PD fluid (Physioneal 3.86%; Baxter Ltd, Castlebar, Ireland) and dextran 70 as a volume marker. The results of these PETs were compared to those of a historic group of 12 children (mean age 75 months, mean time on PD 17 months). SETTING: Pediatric dialysis unit in a tertiary institute. PATIENTS: Stable pediatric PD patients. MAIN OUTCOME MEASURES: Transcapillary ultrafiltration (TCUF) and marker clearance, dialysate-to-plasma (D/P) ratios for urea and creatinine, and D(t)/D(0) ratio for glucose. RESULTS: TCUF and lymphatic absorption were not different between the two groups. There was also no significant difference in small solute clearance measured by D/P ratio for urea and creatinine and D(t)/D(0) ratio for glucose. CONCLUSION: Peritoneal fluid kinetics is not significantly altered if pH-neutral dialysis solutions are applied compared to acidic solutions. An altered TCUF, as is hypothetically possible using an acidic solution, was not established.     

Peritoneal Resting with Heparinized Lavage Reverses Peritoneal Type I Membrane Failure. A Comparative Study of the Resting Effects on Normal Membranes

♦ Background: Ultrafiltration failure (UFF) is a serious complication of long-term peritoneal dialysis (PD). Peritoneal rest (PR) has been demonstrated as a valid treatment to reverse the functional changes that occur in UFF. The effects of PR on a normally functioning human peritoneum are unknown but are expected to be neutral. Our hypothesis was that PR positively modifies peritoneal function in patients with UFF, in contrast to the absence of effects when PR is applied under normal conditions.♦ Patients and Methods: We studied 84 PR periods, comparing 35 patients with UFF and 49 controls (resting for abdominal surgery with temporary discontinuation of PD). We analyzed peritoneal transport pre-PR and post-PR by calculating the mass transfer coefficients of creatinine (Cr-MTAC), the dialysate/plasma creatinine ratio (D/P Cr) and the ultrafiltration (UF).♦ Results: Baseline data was similar for the 2 groups, although the UFF group had a longer median time in PD (39 [18 - 60] vs 10 [5 - 23] months; p = 0.00001). Peritoneal rest induced a decrease in D/P Cr, Cr-MTAC and an increase in UF capacity in the UFF group (p = 0.0001, p = 0.004 and p = 0.001, respectively), without causing changes in the control group. Peritoneal rest in patients with more than 6 months of UFF was not able to reduce peritoneal solute transport or improve UF capacity. Response to PR did not differ among UFF patients with or without a previous history of peritonitis. Peritoneal rest enabled patients with UFF to continue on PD for a median time of 23 months (range, 13 - 46 months).♦ Conclusions: Peritoneal rest induces functional changes in patients with UFF but not in those with no functional abnormalities. This demonstrates that PR works only when abnormal but reversible functional conditions are present. However, the effect is highly dependent on how early PR is applied.     

腹膜透析患者肠系膜上动脉血流动力学改变及其与腹膜超滤功能的相关性

目的 彩色多普勒超声评价腹膜透析患者肠系膜上动脉血流动力学改变,探讨其与腹膜超滤功能的相关性.方法 应用Philips飞凡型彩色多普勒诊断仪对40例尿毒症腹膜透析患者(按透析时间分为两组,BⅠ组透析时间＜1年,BⅡ组透析时间≥1年)及20例尿毒症非透析患者(A组)肠系膜上动脉血流动力学参数进行测定.结果 (1)三组管径(D)、收缩期峰值速度(PSV)无统计学差异(P>0.05).BⅡ组舒张末期速度(EDV)、时间平均速度(TAVM)、血流量(Q)较A组及BⅠ组均明显增高(P<0.01),阻力指数(RI)、搏动指数(PI),BⅡ较A组及BⅠ组明显降低(P<0.01),而A组与BⅠ组上述参数均无统计学差异(P>0.05).(2)腹膜超滤量BⅡ较BⅠ组明显降低,差异有统计学意义(P<0.01).(3)BⅠ、BⅡ两组患者RI、PI与透析时间呈负相关(r=-0.89,P<0.01,r=-0.436,P<0.01 ),腹膜超滤量与透析时间呈负相关(r=-0.599,P<0.01);腹膜超滤量与RI、PI呈正相关(r=0.677、P<0.01,r=0.554、P<0.01).结论 彩色多普勒超声可以无创地评价尿毒症腹膜透析患者肠系膜上动脉血流动力学改变,进而了解腹膜透析对腹膜功能的影响,其中RI、PI的下降对腹膜超滤功能的损害有重要的提示意义.     

Risk factors responsible for ultrafiltration failure in early stages of peritoneal dialysis.

OBJECTIVE: To define risk factors for ultrafiltration failure (UFF) during early stages of peritoneal dialysis (PD). DESIGN: Retrospective analysis of a group of patients whose peritoneal function was prospectively followed. SETTING: A tertiary-care public university hospital. PATIENTS: Nineteen of 90 long-term PD patients required a peritoneal resting period to recover UF capacity: 8 had this requirement before the third year on PD (early, EUFF group) and 11 had a late requirement (LUFF group). The remaining 71 patients, those with stable peritoneal function over time, constituted the control group. MAIN OUTCOME MEASURES: Peritoneal UF capacity under standard conditions (monthly) and small solute peritoneal transport (yearly). RESULTS: None of the conditions appearing at the start of PD or during the observation period could be definitely identified as the cause of UFF. There were no differences in characteristics between the EUFF group and the other two groups, except for the higher prevalence of diabetes in the EUFF group. Residual renal function (RRF) declined in all three groups during the first 2 years, with rapid loss during the third year in the EUFF group. This rapid loss in RRF was coincident with UFF. Peritoneal solute and water transport at baseline was similar in the three groups. After 2 years on PD, individuals in the EUFF group showed a significantly lower UF and higher creatinine mass transfer coefficient values than those in the LUFF group. Diabetic patients in the control group showed remarkable stability in UF capacity over time. During the second year on PD, requirement for increases in dialysate glucose concentration was 3.4 +/- 0.5% in the LUFF group, but as high as 25.5 +/- 24.2% in the EUFF group. The accumulated days of active peritonitis (APID, days with cloudy effluent) were similar for the three groups after 1, 2, and 3 years on PD. Interestingly, diabetic patients in the control group showed an APID index significantly lower than the overall EUFF group. Diabetics in the control group also had significantly lower APID versus nondiabetics in the control group (p = 0.016). CONCLUSIONS: Our findings suggest that certain patients develop early UFF type I. Diabetic state and a higher glucose requirement to obtain adequate UF suggest that glucose on both sides of the peritoneal membrane could be responsible. The mechanisms for this higher requirement remain to be elucidated. The identification of a larger cohort of these early UFF patients should lead to a better exploration of the primary pathogenic mechanisms.     

Does lymphatic absorption change with the duration of peritoneal dialysis?

BACKGROUND: Ultrafiltration failure is an important complication of long-term peritoneal dialysis (PD). A high effective lymphatic absorption rate (ELAR) can contribute to impaired ultrafiltration. It is unknown whether the ELAR increases with time on PD. OBJECTIVE: The relationship between the ELAR and duration of PD was analyzed, as well as the correlation between the ELAR and other transport parameters. We also studied the relation between the ELAR and cancer antigen 125 (CA125) a marker for mesothelial cell mass. SETTING: Peritoneal dialysis unit in the Academic Medical Center, Amsterdam. DESIGN: Cross-sectional and longitudinal studies of standard peritoneal permeability analyses (SPAs; 4-hour dwells, dextran 70 as a volume marker) with glucose 3.86% in 130 PD patients. METHODS: SPAs were analyzed in 130 stable PD patients (77 males). Median duration of PD was 25 months (range 1-214) in a cross-sectional study. The last SPA from each patient was analyzed. The longitudinal analysis included 24 patients (12 males) from whom at least 3 SPAs were available with a minimum interval of 8 months. Dextran 70, 1 g/L, was administered intraperitoneally at the initiation of the test. Lymphatic absorption was calculated from the disappearance rate of dextran 70 during the 4-hour dwell. Therefore, the ELAR included both transmesothelial and subdiaphragmatic uptake of dextran 70. RESULTS: Median ELAR was 1.43 mL/minute (range 0.17- 6.59 mL/minute). No relationship was found between the ELAR and duration of PD in the cross-sectional analysis, nor was there a trend in time for 20 of the 24 patients studied longitudinally. In 4 patients, a negative trend was found. None of these had ultrafiltration failure and all 4 patients had a different cause for end-stage renal failure. The ELAR was correlated with parameters of peritoneal solute transport, but not with CA125 when investigated in a cross-sectional analysis. Only after 48 months of PD treatment was a significant relationship between the ELAR and CA125 seen (r = 0.46, p < 0.05). CONCLUSIONS: No time trend is present for the effective peritoneal lymphatic absorption rate, and it is not associated with patient or technique survival. Although increased lymphatic absorption is one of the causes of ultrafiltration failure, it is unlikely to contribute to the development of ultrafiltration failure in long-term PD patients with well-maintained transcapillary ultrafiltration.     

Does enalapril prevent peritoneal fibrosis induced by hypertonic (3.86%) peritoneal dialysis solution?

OBJECTIVE: Peritoneal fibrosis (PF) is one of the most serious causes of failure in continuous ambulatory peritoneal dialysis (PD). Although the underlying mechanism responsible for the genesis of PF is still unknown, transforming growth factor beta (TGFbeta1) has been shown to be associated with PF. Angiotensin converting enzyme inhibitors have been shown to prevent the stimulating effect of growth factors. The aim of the present study was to investigate the effect of enalapril on peritoneal function and morphology in a rat model of experimental PF. METHODS: Twenty-one albino Wistar rats were divided into three groups: (1) the control group (C) received 10 mL isotonic saline intraperitoneally (i.p.), (2) the dextrose (Dx) group 10 mL 3.86% dextrose PD solution i.p., and (3) the enalapril-treated group (ENA) 10 cc 3.86% dextrose PD solution i.p. plus 100 mg/L enalapril in drinking water. After 4 weeks, a 1-hour peritoneal equilibration test was performed with 20 mL 2.27% dextrose PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration (UF) volume, and levels of dialysate protein, TGFbeta1, and cancer antigen 125 (CA125) were determined. The parietal peritoneum was evaluated histologically by light microscopy. RESULTS: Administration of enalapril resulted in preserved UF (-0.2 +/- 0.7 mL vs 1.7 +/- 0.3 mL, p < 0.05), protein loss (2.3 +/- 0.5 g/L vs 1.6 +/- 0.2 g/L, p > 0.05), and peritoneal thickness (77 +/- 7 microns vs 38 +/- 5 microns, p < 0.001). D/P urea increased significantly in the Dx group (p< 0.05). Both higher levels of TGFbeta1 (undetectable vs 298 +/- 43 pg/mL, p < 0.001) and lower levels of CA125 in dialysate effluent (0.94 +/- 0.5 U/L vs 0.11 +/- 0.1 U/L, p > 0.05) were determined in the Dx group. CONCLUSION: These findings show that peritoneal morphology and function tests were dramatically deranged in the Dx group. The same properties were partially preserved in the ENA group. The production of TGFbeta1 was significantly reduced but peritoneal thickness was not completely inhibited. In conclusion, by inhibiting the production of TGFbeta1, enalapril can preserve peritoneal histology, peritoneal function, and remodeling of mesothelial cells.     

腹膜纤维化机制与治疗新进展

腹膜透析作为一种有效的肾脏替代治疗,在终末期肾病中运用日渐广泛,甚至成为肾脏替代治疗的首选方案。但长期的腹膜透析会导致腹膜功能下降、腹膜结构改变,最终演变成腹膜纤维化,甚至包裹性腹膜硬化症,使超滤失败,严重时使患者退出腹膜透析。目前国内外研究主要包括:上皮细胞一间充质转化、腹膜透析液的生物不相容性、血管紧张素一醛固酮系统、氧化应激、腹膜炎症、全身微炎症状态、基因调控、生长及转化因子等,针对上述发病机制,提出了相应的治疗方法。      

Ex vivo analysis of dialysis effluent-derived mesothelial cells as an approach to unveiling the mechanism of peritoneal membrane failure.

During peritoneal dialysis (PD), the peritoneum is exposed to bioincompatible dialysis fluids, which causes progressive fibrosis and angiogenesis and, ultimately, ultrafiltration failure. In addition, repeated episodes of peritonitis or hemoperitoneum may accelerate all these processes. Fibrosis has been classically considered the main cause of peritoneal membrane functional decline. However, in parallel with fibrosis, the peritoneum also displays increases in capillary number (angiogenesis) and vasculopathy in response to PD. Nowadays, there is emerging evidence pointing to peritoneal microvasculature as the main factor responsible for increased solute transport and ultrafiltration failure. However, the pathophysiologic mechanism(s) involved in starting and maintaining peritoneal fibrosis and angiogenesis remain(s) elusive. Peritoneal stromal fibroblasts have been considered (for many years) the cell type mainly involved in structural and functional alterations of the peritoneum; whereas mesothelial cells have been considered mere victims of peritoneal injury caused by PD. Recently, ex vivo cultures of effluent-derived mesothelial cells, in conjunction with immunohistochemical analysis of peritoneal biopsies from PD patients, have identified mesothelial cells as culprits, at least in part, in peritoneal membrane deterioration. This review discusses recent findings that suggest new peritoneal myofibroblastic cells may arise from local conversion of mesothelial cells by epithelial-to-mesenchymal transition during the repair responses that take place in PD. The transdifferentiated mesothelial cells may retain a permanent mesenchymal state, as long as initiating stimuli persist, and contribute to PD-induced fibrosis and angiogenesis, and hence to membrane failure. Future therapeutic interventions could be designated in order to prevent or reverse epithelial-to-mesenchymal transition of mesothelial cells, or its pernicious effects.     

The clinical usefulness of peritoneal dialysis fluids with neutral pH and low glucose degradation product concentration: an open randomized prospective trial

BACKGROUND: Long-term peritoneal dialysis (PD) is associated with the development of various structural and functional changes to the peritoneal membrane when bioincompatible conventional peritoneal dialysis fluids (PDFs) are used. In this study, we looked at patients that were treated with conventional PDFs and then changed to novel biocompatible PDFs with a neutral pH and a low concentration of glucose degradation products (GDPs) to investigate whether this change could result in the arrest or reversal of peritoneal membrane deterioration. METHODS: In an open label, randomized prospective trial, the clinical effects of conventional PDFs and biocompatible PDFs with neutral pH and very low concentration of GDPs were compared in 104 patients equally divided between both study PDFs. Blood and effluent dialysate samples, peritoneal equilibration tests, and adequacy evaluation were undertaken at baseline, 4, 8, and 12 months. The target variables were the ratio of dialysate-to-plasma (D/P) creatinine, peritoneal ultrafiltration, residual renal function, dialysis adequacy indices, and effluent cancer antigen 125 (CA125). RESULTS: D/P creatinine values were not different in the two groups. Peritoneal ultrafiltration was significantly higher in the low-GDP PDF group than in the conventional PDF group at all follow-up times (4 months: 9.1 +/- 4.3 vs 6.0 +/- 3.0; 8 months: 8.3 +/- 3.4 vs 6.0 +/- 3.0; 12 months: 8.9 +/- 3.3 vs 6.1 +/- 3.3 mL/g dextrose/day; p < 0.05). Peritoneal Kt/V urea values and total weekly Kt/V urea values at 4 months were significantly higher in the low-GDP PDF group than in the conventional PDF group. Residual renal function was not statistically significant. Effluent CA125 levels were significantly higher in the low-GDP PDF group at all follow-up visits (4 months: 37.8 +/- 20.8 vs 22.0 +/- 9.5; 8 months: 41.2 +/- 20.3 vs 25.9 +/- 11.3; 12 months: 40.4 +/- 21.4 vs 28.6 +/- 13.0 U/mL; p < 0.05). Among anuric patients, peritoneal ultrafiltration at 4, 8, and 12 months, total weekly Kt/V at 4 and 8 months, and CA125 levels at all follow-up visits were significantly higher in patients treated with low-GDP PDF than those treated with conventional PDF. However, among anuric patients, D/P creatinine showed no significant differences between the low-GDP PDF group and the conventional PDF group. CONCLUSION: The use of biocompatible PDFs with neutral pH and low GDP concentration can contribute to improvement of peritoneal ultrafiltration and peritoneal effluent CA125 level, an indicator of peritoneal membrane integrity in PD patients.     

Is technique survival on peritoneal dialysis better in Japan?

Technique failure resulting in transfer to hemodialysis (HD) remains one of the most important challenges in Longterm peritoneal dialysis (PD). In general, the proportion of patients transferring from PD to HD is much greater than the proportion transferring from HD to PD. However, technique failure rates differ considerably between and within countries. The question arises as to how technique failure rates in Japan compare with those in other countries. To address this issue, we reviewed the literature and our experience of 139 incident continuous ambulatory peritoneal dialysis (CAPD) patients from January 1995 to December 1999. Based on our review, we estimate that the 5-year technique survival rate in Japanese CAPD patients is approximately 70%, and that technique failure rate is around 7% per year. This rate is significantly lower than that in many other countries. The most common reasons for technique failure in Japan are peritoneal membrane failure, ultrafiltration loss, and inadequate dialysis. Another factor contributing to the low technique failure rate in Japan is an extremely low peritonitis rate. This may be related to good sanitation and excellent PD training programs. Peritoneal membrane failure continues to be the major challenge for long-term technique survival on PD in Japan.     

The Mutual Relationship Between Peritonitis and Peritoneal Transport

♦ Background:

Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport.

♦ Methods:

Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16).

♦ Results:

At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport.

♦ Conclusions:

Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD.     

The Role of Tyrosine Kinase Receptors in Peritoneal Fibrosis

Peritoneal dialysis (PD) is a modality for treatment of patients with end-stage renal disease (ESRD) that depends on the structural and functional integrity of the peritoneal membrane. However, long-term PD can lead to morphological and functional changes in the peritoneum; in particular, peritoneal fibrosis has become one of the most common complications that ultimately results in ultrafiltration failure (UFF) and discontinuation of PD. Several factors and mechanisms such as inflammation and overproduction of transforming growth factor-β1 have been implicated in the development of peritoneal fibrosis, but there is no effective therapy to prevent or delay this process. Recent studies have shown that activation of multiple receptor tyrosine kinases (RTKs) is associated with the development and progression of tissue fibrosis in various organs, and there are also reports indicating the involvement of some RTKs in peritoneal fibrosis. This review will describe the role and mechanisms of RTKs in peritoneal fibrosis and discuss the possibility of using them as therapeutic targets for prevention and treatment of this complication.     

Can EPS Development Be Avoided with Early Interventions? The Potential Role of Tamoxifen—A Single-Center Study

♦ Background: Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Identification of patients at high risk for EPS (“EPS-prone”) and delivery of appropriate interventions might prevent its development. Our aim was to evaluate the clinical characteristics and outcomes of all EPS and EPS-prone patients diagnosed at our PD unit.♦ Methods: For a 30-year period representing our entire PD experience, we retrospectively identified all patients with EPS (diagnosed according to International Society for Peritoneal Dialysis criteria) and all patients defined as EPS-prone because they met at least 2 established criteria (severe peritonitis, PD vintage greater than 3 years, severe hemoperitoneum, overexposure to glucose, and acquired ultrafiltration failure).♦ Results: Of 679 PD patients, we identified 20 with EPS, for an overall prevalence of 2.9%. Mean age at diagnosis was 50.2 ± 16.4 years, with a median PD time of 77.96 months (range: 44.36 - 102.7 months) and a median follow-up of 30.91 months (range: 4.6 - 68.75 months). Of patients with EPS, 10 (50%) received tamoxifen, 10 (50%) received parenteral nutrition, and 2 (10%) underwent adhesiolysis, with 25% mortality related to EPS. Another 14 patients were identified as EPS-prone. Median follow-up was 54.05 months (range: 11.9 - 87.04 months). All received tamoxifen, and 5 (36%) received corticosteroids; none progressed to full EPS. We observed no differences in baseline data between the groups, but the group with EPS had been on PD longer (84 ± 53 months vs 39 ± 20 months, p = 0.002) and had a higher cumulative number of days of peritoneal inflammation from peritonitis (17.2 ± 11.1 days vs 9.8 ± 7.9 days, p = 0.015). Overall mortality was similar in the groups. The incidence of EPS declined during our three decades of experience (5.6%, 3.9%, and 0.3%).♦ Conclusions: Being a serious, life-threatening complication of PD, EPS requires high suspicion to allow for prompt diagnosis and treatment. Early detection of EPS-prone states and delivery of appropriate intervention might prevent EPS development. Tamoxifen seems to be a key strategy in prevention, but caution should be used in interpreting our results. Additional randomized controlled studies are needed.     

Dissociation between clearances of small and middle molecules in incremental peritoneal dialysis.

OBJECTIVE: To evaluate the peritoneal clearance of middle molecules in comparison with the peritoneal clearance of small molecules in incremental peritoneal dialysis (PD). STUDY DESIGN: Peritoneal clearances of creatinine and beta2-microgloblulin (B2M) were compared in 57 continuous ambulatory PD patients on full dose of 4 exchanges, and 54 incremental PD patients with 2 or 3 exchanges over 24 hours. Clearances were also compared when there were changes in the PD regimen, such as in the number of exchanges and the duration of the dwell time. SETTING: Tertiary-care university hospital. RESULTS: Peritoneal creatinine clearance increased almost linearly with the increase in the number of exchanges. In contrast, peritoneal clearance of B2M was 9.1 +/- 3.6 L/week, 8.8 +/- 4.4 L/week, and 7.9 +/- 2.5 L/week with 2,3, and 4 exchanges, respectively, per day, amounts that were not different from each other. Peritoneal clearance of B2M did not change when there was an increase in the number of dialysate exchanges from 2 to 3 and from 3 to 4 over a period of 24 hours; whereas the peritoneal clearance of creatinine increased. Peritoneal clearance of B2M almost doubled, from 5.4 +/- 2.7 L/week with 2 exchanges over 12 hours per day, to 9.5 +/- 4.4 L/week with the same 2 exchanges over 24 hours. The creatinine clearance did not change. CONCLUSION: In contrast to peritoneal clearance of small molecules, such as creatinine, which was dependent on the number of dialysate exchanges, peritoneal clearance of middle molecules, such as B2M, depended mainly on the total dwell hours of PD and not on the number of exchanges of peritoneal dialysate in incremental PD. This might be another advantage of incremental PD, since peritoneal clearance of middle molecules in incremental PD over 24 hours can be comparable to that in full dose PD.     

Low molecular weight heparin improves peritoneal ultrafiltration and blocks complement and coagulation.

OBJECTIVES: Clinical studies have demonstrated that the intraperitoneal (IP) complement and coagulation systems are activated in peritoneal dialysis (PD) patients. In animal models, low molecular weight heparin (LMWH) was seen to inhibit peritoneal angiogenesis, and related compounds have increased ultrafiltration volumes after repeated administration to PD patients. The present study evaluated the effects of LMWH on ultrafiltration, coagulation, and complement activation during a single PD dwell. DESIGN: Rats were exposed to a single dose of 20 mL 2.5% glucose-based, filter-sterilized PD fluid, with or without supplementation with LMWH. The PD fluid was administered either as an IP injection or as an infusion through an indwelling catheter. The dwell fluid was analyzed 2 hours later concerning activation of the complement and coagulation cascades, chemotactic activity, neutrophil recruitment, ultrafiltration volume, and glucose and urea concentrations. RESULTS: Exposure to PD fluid induced activation of IP complement [formation of C3a (desArg) and increase of C5a-dependent chemotactic activity] and coagulation (formation of thrombin-antithrombin complex) and recruitment of neutrophils. In the case of IP injection, neutrophil recruitment and complement activation were inhibited by LMWH. In both models, LMWH inhibited thrombin formation, reduced complement-dependent chemotactic activity, and increased the IP fluid volume, indicating an improved ultrafiltration. CONCLUSIONS: The acute inflammatory reaction to PD fluid involves the complement and coagulation cascades. Addition of LMWH to the PD fluid improves ultrafiltration, inhibits formation of thrombin, and potentially blocks C5a activity. The present results motivate further investigations of the IP cascade systems in PD.     

Effects of peritoneal resting on peritoneal fluid transport kinetics.

BACKGROUND: Peritoneal resting has been used to restore peritoneal ultrafiltration capacity in peritoneal dialysis patients. Therefore, in the present study, we made a detailed investigation on the effects of peritoneal resting on peritoneal fluid transport characteristics in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: A temporary transfer to daytime ambulatory peritoneal dialysis with a nocturnal "empty belly" was applied to let the peritoneal membrane rest overnight in patients with poor ultrafiltration capacity. All included patients were asked to record appropriately their dialysis exchanges for the assessment of peritoneal fluid transport characteristics, which were evaluated before and after peritoneal resting. RESULTS: Seven CAPD patients were included in the present study. There was a significant improvement in peritoneal ultrafiltration capacity as assessed by ultrafiltration volume per gram of glucose load. Patients' daily glucose exposure and dialysate-to-plasma ratio of creatinine were significantly decreased after peritoneal resting. The peritoneal fluid absorption rate was also significantly decreased after peritoneal resting: 1.011 +/- 0.4484 versus 0.625 +/- 0.3833 mL/minute. CONCLUSION: The present study suggests that peritoneal resting can improve CAPD patients' ultrafiltration capacity and decrease the use of hypertonic dialysis solution. The improved ultrafiltration capacity by peritoneal resting was due to decreased membrane solute transport rate and decreased peritoneal fluid absorption rate.     

Serum BNP concentration and left ventricular mass in CAPD and automated peritoneal dialysis patients.

OBJECTIVE: To compare ultrafiltration under continuous ambulatory peritoneal dialysis (CAPD) and automated PD (APD), disclosing potential effects on serum B-type natriuretic peptide (BNP) levels and echocardiographic findings. PATIENTS AND METHODS: This cross-sectional clinical study included 32 patients on CAPD and 30 patients on APD without clinical evidence of heart failure or hemodynamically significant valvular heart disease. Peritoneal equilibration tests, BNP levels, and echocardiographic measurements were performed in each subject. BNP measurements were also performed in 24 healthy control subjects. RESULTS: Patients on APD had lower ultrafiltration and higher values of BNP and left ventricular mass index (LVMI) compared with patients on CAPD (respectively: 775 +/- 160 vs 850 +/- 265 mL, p = 0.01; 253.23 +/- 81.64 vs 109.42 +/- 25.63 pg/mL, p = 0.001; 185.12 +/- 63.50 vs 129.30 +/- 40.95 g/m(2), p = 0.001). This occurred despite higher mean dialysate glucose concentrations and far more extensive use of icodextrin in the APD group. CONCLUSION: Treatment with APD is associated with higher plasma BNP levels and LVMI compared to CAPD. This may be the result of chronic fluid retention caused by lower ultrafiltration in APD patients.