Peritoneal function in clinical practice: the importance of follow-up and its measurement in patients. Recommendations for patient information and measurement of peritoneal function

A review is given on peritoneal function, especially ultrafiltration and ultrafiltration failure followed by recommendations on how to translate pathophysiology into clinical practice. The subsequent consequences for management of peritoneal membrane function and for patient information are also included

Update on potential medical treatments for encapsulating peritoneal sclerosis; human and experimental data

Encapsulating peritoneal sclerosis (EPS) is an infrequent but serious complication of peritoneal dialysis (PD). The pathogenesis is unknown but speculation is ongoing. The current management of EPS focuses on prevention and treatment of the inflammatory and fibrotic changes at the level of the peritoneal membrane with immunosuppressive and antifibrotic agents, respectively. This article reviews the currently available human and animal data on potential agents to prevent and/or treat EPS. We propose a strategy for early diagnose EPS in an attempt to avoid the development of the full-blown and potentially life-threatening clinical syndrome of EPS. Future research should focus on studying potential prophylactic and therapeutic agents in humans in large, multicenter, randomized trials but also on early detection of EPS in the inflammatory phase by means of biomarkers and the establishment of a composite EPS score

Peritoneal equilibration test with conventional ‘low pH/high glucose degradation product’ or with biocompatible ‘normal pH/low glucose degradation product’ dialysates: does it matter?

Abstract Background. The evaluation of the peritoneal transport characteristics is mandatory in peritoneal dialysis (PD) patients. This is usually performed in routine clinical practice with a peritoneal equilibration test (PET) using conventional dialysates, with low pH and high glucose degradation product (GDP) concentrations. An increasing proportion of patients are now treated with biocompatible dialysates, i.e. with physiological pH and lower GDP concentrations. This questions the appropriateness to perform a PET with conventional solutions in those patients. The aim of our study is to compare the results of the PET using biocompatible and conventional dialysates, respectively. Methods. Nineteen stable PD patients (13 males, 6 females; mean age: 67.95 ± 2.36 years, mean body surface area: 1.83 ± 0.04 m2, dialysis vintage: 2.95 ± 0.19 years) were included, among which 10 were usually treated with biocompatible and 9 with conventional solutions. Two PETs were performed, within a 2-week interval, in each patient. PET sequence (conventional solution first or biocompatible solution first) was randomized in order to avoid ‘time bias’. Small (urea, creatinine and glucose), middle (beta-2-microglobulin) and large molecules’ (albumin and alpha-2-macroglobulin) dialysate/plasma (D/P) concentration ratios and clearances were measured during each PET. Ultrafiltration (UF) and sodium filtration were also recorded. Results of both tests were compared by the Wilcoxon paired test. Results. No statistical difference was found between both dialysates for small molecule transport rates or for sodium filtration and UF. However, a few patients were not similarly classified for small-solute transport characteristics within the PET categories. Beta-2-microglobulin and albumin D/P ratios at different time points of the PET were significantly higher with the biocompatible, when compared with the conventional, solutions: 0.10 ± 0.03 versus 0.08 ± 0.02 (P < 0.01) and 0.008 ± 0.003 versus 0.007 ± 0.003 (P = 0.01), respectively. A similar difference was also observed for beta-2-microglobulin that was higher with biocompatible dialysates (1.04 ± 0.32 versus 0.93 ± 0.32 mL/min, respectively). Conclusion. Peritoneal transport of water and small solutes is independent of the type of dialysate which is used. This is not the case for the transport of beta-2-microglobulin and albumin that is higher under biocompatible dialysates. Vascular tonus modification could potentially explain such differences. The PET should therefore always be carried out with the same dialysate to make longitudinal comparisons possible

Non-invasive assessment of peritoneal membrane alterations

The peritoneal dialysis membrane is subject to remodelling in the course of peritoneal dialysis. In the absence of longitudinal morphological studies, this process is mainly studied indirectly by the investigation of changes in peritoneal transport. Non-invasive assessment of the peritoneum is also possible by assessment of substances that originate from peritoneal tissues and can be determined either as their gene expression in peritoneal effluent cells and/or as proteins in peritoneal effluent. Three of these biomarkers will be discussed, because longitudinal data are available.&#x0D; Cancer antigen 125 (CA 125) is present on the mesothelium,while its gene (MUC 16) is expressed in peritoneal effluent cells and is related to dialysate CA 125 protein. The constitutive production and the small intra-individual variability of 15% indicate its usefulness as a follow-up marker of mesothelial cell mass. Dialysate appearance rate is higher on biocompatible than on conventional solutions, but both decrease during long-term follow-up.&#x0D; Interleukin-6 (Il-6) is present in peritoneal effluent due to both transport from the circulation and local intraperitoneal production. Its appearance rate is unrelated to its gene expression in peritoneal cells. The intra-individual variation of effluent Il-6 averages 28%, hampering the interpretation of cross-sectional values. The relationships between effluent Il-6 and peritoneal transport have been interpreted as microinflammation, but are difficult to interprete due to mathematical coupling.&#x0D; Plasminogen activator inhibitor-1 (PAI-1) is encoded by the SERPINE 1 gene. A relationship is present between effluent concentration and gene expression. PAI-1 production is stimulated by glucose. PAI-1 appearance rate increases with PD duration. The sensitivity of effluent PAI-1 for the diagnosis of encapsulating peritoneal sclerosis was 100% one year prior to the diagnosis and the specificity 56%.&#x0D; It can be concluded that the discussed biomarkers are useful extensions to transport in assessment of the peritoneum during dialysis.&#x0D;  </jats:p

Relative Contributions of Pseudohypoxia and Inflammation to Peritoneal Alterations with Long-Term Peritoneal Dialysis Patients

Long-term peritoneal dialysis is associated with alterations in peritoneal function, like the development of high small solute transfer rates and impaired ultrafiltration. Also, morphologic changes can develop, the most prominent being loss of mesothelium, vasculopathy, and interstitial fibrosis. Current research suggests peritoneal inflammation as the driving force for these alterations. In this review, the available evidence for inflammation is examined and a new hypothesis is put forward consisting of high glucose-induced pseudohypoxia. Hypoxia of cells is characterized by a high (oxidized-reduced nicotinamide dinucleotide ratio) NADH-NAD+ ratio in their cytosol. Pseudohypoxia is similar but occurs when excessive amounts of glucose are metabolized, as is the case for peritoneal interstitial cells in peritoneal dialysis. The glucose-induced high NADH-NAD+ ratio upregulates the hypoxia-inducible factor-1 gene, which stimulates not only the glucose transporter-1 gene but also many profibrotic genes like TGFβ, vascular endothelial growth factor, plasminogen activator inhibitor-1, and connective tissue growth factor, all known to be involved in the development of peritoneal fibrosis. This review discusses the causes and consequences of pseudohypoxia in peritoneal dialysis and the available options for treatment and prevention. Reducing peritoneal exposure to the excessively high dialysate glucose load is the cornerstone to avoid the pseudohypoxia-induced alterations. This can partly be done by the use of icodextrin or by combinations of low molecular mass osmotic agents, all in a low dose. The addition of alanyl-glutamine to the dialysis solution needs further clinical investigation

Migration in Russia: Pros and Cons

This article deals with the positive and negative consequences of foreign labour migration in Russia. The authors emphasize that Russia is not a homogeneous country. The socio-economic implications for regions diff er. This study has found foreign labour migration to be a complicated socio-economic phenomenon, which has a dual eff ect on the labor market in Russia: on the one hand it is filling the gap in the labour force caused by the demographic crisis; on the other hand it increases the tension on the labour market because of migrants