RESUMEN

BACKGROUND: No diagnostic tool or methodology is currently available for early detection of imminent encapsulating peritoneal sclerosis (EPS). The objective of this study was to investigate the predictive value of free water transport (FWT) and construct a panel of peritoneal effluent proteins for EPS alone or in combination with FWT. These parameters could be incorporated in the follow-up of peritoneal dialysis (PD) patients. METHODS: A case-control study, nested in a longitudinal PD patient cohort, was conducted. Time-specific areas under the receiver operating characteristic (ROC) curve were calculated for FWT and effluent biomarkers at a lag time up to 3 years before EPS diagnosis. Free water transport was combined with appearance rates (AR) of biomarkers to assess their clinical validity. RESULTS: Free water transport volume and AR of effluent biomarkers were investigated in 11 EPS patients and 34 long-term PD patients. Diagnostic performance was best for FWT (area under the curve [AUC] 0.94) followed by plasminogen activator inhibitor (PAI-1) AR. Throughout, diagnostic panels of FWT and AR of cancer antigen 125 (CA125), interleukin-6 (IL-6), or (PAI-1) yielded specificity estimates above 84%. The combination of FWT and PAI-1 AR identified the largest proportion of EPS patients at 1 year prior to diagnosis (sensitivity 100%, specificity 94%). CONCLUSION: Measurement of FWT is simple and has the highest predictive value for imminent EPS. The addition of effluent biomarkers provides an all-round insight into the state of the peritoneum. Our data indicate that combining FWT with either PAI-1, CA125, or IL-6 has the highest specificity. This is required to avoid unnecessary discontinuation of PD treatment.

Asunto(s)

RESUMEN

Qualitative assessments in long-term patients and in those with encapsulating peritoneal sclerosis (EPS) have shown that impaired osmotic conductance is likely a factor contributing to the presence of ultrafiltration failure in those individuals. In the present study, we investigated the value of osmotic conductance, its components LpA and the reflection coefficient sigma, and free water transport (FWT) in 12 patients with EPS, in 21 patients with long-term ultrafiltration failure, and in 26 time-restricted control subjects with normal ultrafiltration. A decrease in all parameters was observed during a period of 4 years in patients with EPS and ultrafiltration failure, with FWT showing the largest difference between all three groups; however, the receiver operating curves showed that only FWT appeared to be a significant predictor of EPS. Because its measurement is simple, FWT should be included in the regular assessment of peritoneal function.

Asunto(s)

RESUMEN

BACKGROUND: Functional variants in the IL6 gene, in particular the -174G/C polymorphism (rs1800795), affect the mortality risk in dialysis patients. Peritoneal dialysis (PD) patients harbouring the C allele of the -174G/C polymorphism of IL6 showed faster peritoneal transport. The aim of this study was to investigate this IL6 variant as risk factor for mortality and technique failure in a large cohort of Caucasian PD patients. METHODS: A Dutch multicentre cohort of 398 incident PD patients (NECOSAD) was analysed. Survival analysis was performed for death and technique failure with a maximum follow-up of 5 years. A combined PD cohort from Amsterdam (Academic Medical Center, N = 71) and Brussels (Université catholique de Louvain Medical School, N = 102) was used for independent replication. RESULTS: In NECOSAD, 105 patients died on dialysis [incidence rate 10.3/100 person-years (py)], and 138 patients experienced technique failure (16.2/100 py), with peritonitis as important cause. Patients with the C/C genotype had a 71% increased mortality risk compared to patients with the G/G genotype (95% confidence interval 0.98-2.98); this effect was mainly a long-term effect: a 2.7-fold increased mortality risk was found in patients having survived 2 years since the start on dialysis, and a 1.7-fold increased risk for the combined end point (mortality or technique failure). In the combined replication cohort, no increased risks were found in patients with the C/C genotype. CONCLUSIONS: The C/C genotype of the -174G/C polymorphism was associated with an increased mortality risk in 398 Dutch incident PD patients. The existence of substantial differences between the two academic replication cohorts and the discovery cohort from NECOSAD and the limited power of these cohorts prevented an independent replication of the NECOSAD findings.

Asunto(s)

RESUMEN

Models of encapsulating peritoneal sclerosis (EPS) are often based on local administration of chemical irritants. Our aim was to develop a clinically relevant "two-hit" model with incorporation of renal failure and exposure to conventional dialysis solutions. We randomly allocated 36 male Wistar rats that had undergone catheter implantation and a 70% nephrectomy to 3 peritoneal infusion groups. The experimental group was exposed to a 3.86% glucose-based conventional dialysis solution for 8 weeks, after which the animals received a second hit of intraperitoneal blood administration. Two weeks later the rats were humanely euthanized The two control groups were exposed to the conventional dialysis solution alone or to a buffer without glucose for 8 weeks. All animals underwent a peritoneal function test at the end of the experiment. Peritoneal adhesions were counted at autopsy, and omental tissue was obtained for morphometrics. The rats that received blood as a second hit developed numerous intraperitoneal adhesions as seen in EPS, but without cocoon formation. Microscopically, no differences in fibrosis scores and vessel counts were observed between the groups. Peritoneal function parameters were also similar in all groups. The short infusion period could be the reason that we found no differences between the groups, with the exception of the large amount of intraperitoneal adhesions in the experimental group. Modifications to the described rat model are required to develop a clinically relevant EPS model. Besides renal failure and long-term exposure to bioincompatibleperitoneal dialysis solutions, a different second hit or several additional hits could be incorporated into an experimental model of EPS.

Asunto(s)

RESUMEN

Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term peritoneal dialysis (PD) with a 50% mortality rate. EPS is characterized by progressive and excessive fibrotic thickening of the peritoneum, leading to encapsulation of the bowels and intestinal obstruction. At present, EPS cannot be detected with certainty during its early stages; however, a progressive loss of ultrafiltration capacity often precedes its development. Studies that attempted to elucidate the pathogenesis of EPS have shown that the duration of exposure to PD fluids is the most important risk factor for EPS, and that young age and possibly the effects of peritonitis are additional contributory factors. The pathophysiology of EPS is probably best described as a multiple-hit process with a central role for transforming growth factor ß. A form of EPS that develops shortly after kidney transplantation has also been recognized as a distinct clinical entity, and may be a common form of EPS in countries with a high transplantation rate. Criteria have been developed to identify EPS by abdominal CT scan at the symptomatic stage, but further clinical research is needed to identify early EPS in asymptomatic patients, to clarify additional risk factors for EPS and to define optimal treatment strategies.

Asunto(s)

RESUMEN

OBJECTIVE: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD) with a multifactorial pathophysiology and possible increasing incidence. The aim of the present study was to evaluate the independent associations of PD duration, age, dialysis fluids, and kidney transplantation with EPS. METHODS: A multicenter case-control study was performed in the Netherlands from 1 January 1996 until 1 July 2007. The population comprised 63 patients with EPS and 126 control patients. Control patients were selected from the national registry and were matched for date of PD start. Associations were analyzed using a log linear regression model. Primary outcome was appearance of EPS. RESULTS: Compared with control patients, patients with EPS were younger at the start of PD (34.7 ± 15.4 years vs. 51.5 ± 14.7 years, p < 0.0001). The cumulative period on PD was longer in EPS patients than in control patients (78.7 ± 37.8 months vs. 32.8 ± 24 months, p < 0.0001), and the cumulative period on icodextrin was also longer in EPS patients (32.7 ± 23.3 months vs. 18.1 ± 15.7 months, p = 0.006). Compared with control patients, more EPS patients underwent kidney transplantation (47 vs. 59, p < 0.0001). With regard to the period after transplantation, the yearly probability of EPS increased in the year after transplantation to 7.5% from 1.75%. In multivariate regression analysis, cumulative PD duration, age at PD start, transplantation, time from last transplantation to EPS, calendar time, time on icodextrin, and ultrafiltration failure were independently associated with EPS. Transfer from PD to hemodialysis for reasons other than suspected EPS could not be identified as a risk factor for EPS. CONCLUSIONS: Duration of PD, age at PD start, kidney transplantation, time since last transplantation, ultrafiltration failure, and time on icodextrin were associated with a higher risk of EPS.

Asunto(s)

RESUMEN

BACKGROUND/AIMS: Currently available rodent models of peritoneal sclerosis are not based on clinically relevant factors: renal failure in combination with exposure to bioincompatible fluids. Our aim was to develop a chronic peritoneal infusion model of peritoneal sclerosis in rats with renal failure. METHODS: Male Wistar rats underwent a catheter implantation and a 70% nephrectomy. They were randomly divided into three peritoneal infusion groups: chlorhexidine gluconate/ethanol (CGE) + Dianeal (Baxter Healthcare, Castlebar, Ireland), CGE + buffer (Physioneal without glucose; Baxter, Nivelles, Belgium) and Dianeal alone. After 8 weeks a peritoneal permeability test was performed and omental tissue was obtained for morphometrics. RESULTS: The CGE + Dianeal group (n = 6) and CGE + buffer (n = 6) group showed high peritoneal clearances of small solutes and proteins, ultrafiltration failure, impaired free water transport, severe fibrosis and high vessel counts, but the groups did not differ significantly. The Dianeal group (n = 6) showed significantly lower clearances of small solutes and proteins, normal ultrafiltration and sodium sieving, and significantly lower fibrosis scores and vessel counts. CONCLUSIONS: Abnormalities seen in peritoneal sclerosis can be induced in a peritoneal infusion model in rats with renal failure. However, the addition of a bioincompatible dialysis solution had no contributing role, probably because the effects were overruled by those of CGE.

Asunto(s)

RESUMEN

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). The first aim was to analyse the risk of EPS in patients who had developed ultrafiltration failure (UFF). The second aim was to identify specific peritoneal transport alterations that distinguish patients with UFF from patients who will develop EPS. METHODS: All patients of this study were treated with PD between July 1995 and December 2008 in the Academic Medical Center, Amsterdam, the Netherlands. Risk analysis: all PD patients who developed UFF after at least 2 years of PD. Peritoneal transport analysis: all patients who had PD for at least 55 months were included: 12 EPS patients, 21 patients with UFF and 26 patients with normal ultrafiltration (UF). The peritoneal function was measured yearly with a standard peritoneal permeability analysis. UFF was defined as net UF < 400 mL after a 4-h dwell with a 3.86% dialysis solution. RESULTS: Risk analysis: Of the 48 UFF patients, 10 eventually developed EPS. Fifty percent of the patients who continued PD for more than 3 years after the establishment of UFF developed EPS. Peritoneal function analysis: No differences were present for the time courses of solute transport and fluid transport between the EPS and the UFF groups. Overall, the EPS and normal UF groups had lower values for the effective lymphatic absorption rate (ELAR) than the UFF group. CONCLUSIONS: The risk of EPS increases with continuation of PD while UFF is present. Transport characteristics are similar between EPS patients and UFF patients without this complication. A constantly low ELAR may distinguish the EPS patients from those with UFF only.

Asunto(s)

RESUMEN

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD) with an increasing incidence. There is no clear consensus on the treatment of EPS, but anecdotal reports indicate improvement in EPS patients treated with tamoxifen. At present, there is no evidence for the effect of tamoxifen treatment in EPS patients. This study investigates the effect of treatment with tamoxifen on survival in EPS patients. METHODS: This study is a retrospective analysis of survival in EPS patients as part of the Dutch multicentre EPS study in the period January 1996 to July 2007. Sixty-three patients with severe EPS were followed up until August 2008. Demographic, patient and PD-related variables of EPS patients were investigated. Patients treated with tamoxifen were compared to patients not treated with tamoxifen. Survival was analysed with multivariate Cox regression analysis. RESULTS: Twenty-four patients were treated with tamoxifen, and 39 were not treated with tamoxifen. The clinical and demographic characteristics were similar for the tamoxifen-treated and non-treated groups. The mortality rate was significantly lower in tamoxifen-treated patients compared to EPS patients not treated with tamoxifen (45.8% vs 74.4%, P=0.03). Survival in tamoxifen-treated patients, adjusted for calendar time, age, use of corticosteroids, presence of functioning transplantation, use of parental nutrition and centre influences was longer in comparison to not-treated patients (HR 0.39, P=0.056). CONCLUSIONS: Tamoxifen treatment in EPS patients is associated with lower mortality and shows a trend to an increased multivariate-adjusted survival. This supports additional use of tamoxifen to treat patients with severe EPS.

Asunto(s)

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

OBJECTIVE: Encapsulating peritoneal sclerosis (EPS) is a severe complication of long-term peritoneal dialysis (PD). The aim of this study was to investigate whether dialysate levels of cancer antigen-125 (CA125), K(+), interleukin (IL)-6, and vascular endothelial growth factor (VEGF) are early diagnostic markers of EPS. Therefore, we analyzed the time courses of the above described dialysate markers in EPS patients and controls. METHODS: Dialysate and serum samples of 11 EPS patients and 31 control patients, all treated with PD for at least 57 months, were longitudinally collected during standard peritoneal permeability analyses. CA125 and IL-6 were measured in dialysate only, K(+) and VEGF were measured in both dialysate and serum. CA125 and IL-6 are expressed as appearance rates (AR). The linear mixed model was used to analyze the time courses. Sensitivity and specificity were calculated based on the results of the last 2 time points. RESULTS: No differences in the time courses of the different markers were present between the groups. For K(+) and VEGF attributed to local production, no differences between the groups were found. However, AR-CA125 was lower during the last 3 years prior to EPS (p < 0.05) and AR-IL-6 tended to be higher 2 years prior to EPS (p = 0.09). The combination of AR-CA125 < 33 U/min and AR-IL-6 > 350 pg/min had a sensitivity of 70% and a specificity of 89% for the development of EPS. CONCLUSIONS: Compared to controls, AR-CA125 showed lower values and AR-IL-6 tended to be higher during the last years prior to the diagnosis of EPS. The sensitivity and specificity of the combination of CA125 and IL-6 indicate their potential use for an early diagnosis of EPS.

Asunto(s)

RESUMEN

Alport syndrome and encapsulating peritoneal sclerosis (EPS) are both rare diseases. Their joint occurrence is highly unlikely. Two patients at our center with Alport syndrome developed EPS. We therefore hypothesized that Alport syndrome might predispose to the development of EPS and that this predisposition might be reflected in a fast peritoneal transport rate at baseline. We compared the mass transfer area coefficient (MTAC) of creatinine and the clearances of albumin, immunoglobulin G, and alpha2-macroglobulin at baseline and for all subsequent available measurements in four patient groups: EPS patients with Alport syndrome, EPS patients without Alport syndrome, Alport patients without EPS, and long-term peritoneal dialysis (PD) patients without EPS. The transport characteristics were obtained during a standard peritoneal permeability analysis. Between July 1995 and December 2008, 5 of 417 PD patients treated at our center had Alport syndrome as their primary kidney disease, and 13 of the 417 developed EPS. Of those 13 EPS patients, 2 had Alport syndrome. We observed no differences in the baseline transport characteristics of the four groups under consideration. Taking all measures of transport characteristics into account, only the MTAC of creatinine was higher in the two EPS groups than in the other two groups (p = 0.01). We could not confirm our hypothesis that Alport syndrome affects peritoneal solute clearances.

Asunto(s)

RESUMEN

A review is given on biomarkers in peritoneal effluent. It comprises methods to distinguish between diffusion and local production. This is followed by examples of various biomarkers. Their potential use is discussed in 4 situations: inherent fast transporters, longitudinal follow-up of patients, biocompatibility testing of new dialysis solutions, and their potential use in the detection of patients who are likely to develop encapsulating peritoneal sclerosis.

Asunto(s)

RESUMEN

Peritoneal sclerosis (PS) is a severe complication of long-term peritoneal dialysis (PD). We therefore investigated whether longitudinal analysis of solute and fluid transport preceding a diagnosis of PS could predict its development. We reviewed all standard peritoneal permeability analyses (SPAs) performed with 3.86% glucose and completed before a diagnosis of PS in all patients (n = 11) in whom that diagnosis was made in our center between 1995 and 2006. Most patients had 4 SPAs available. A linear mixed-model procedure was used to analyze the trends. Transport of small-solutes showed significant inverse U-shaped trends before a diagnosis of PS. This trend held for the mass transport area coefficients of creatinine, urea, and urate (all p < 0.05) and for their dialysate-to-plasma ratios (all p < 0. 001). Net ultrafiltration and free water transport at 60 minutes showed significant downward linear trends (both p < or = 0. 01). This U-shaped trend in small-solute transport combined with an ongoing decrease in net ultrafiltration and free water transport might be a warning sign of the development of PS. It underlines the importance of regular assessment of peritoneal function with 3.86% peritoneal equilibration tests in every PD patient-not only those at risk for peritoneal membrane failure.

Asunto(s)