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      Alterations of peritoneal transport characteristics in dialysis patients with ultrafiltration failure: tissue and capillary components

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          Abstract

          Background

          Ultrafiltration failure (UFF) in peritoneal dialysis (PD) patients is due to altered peritoneal transport properties leading to reduced capacity to remove excess water. Here, with the aim to establish the role of local alterations of the two major transport barriers, peritoneal tissue and capillary wall, we investigate changes in overall peritoneal transport characteristics in UFF patients in relation to corresponding local alterations of peritoneal tissue and capillary wall transport properties.

          Methods

          Six-hour dwell studies using 3.86% glucose solutions and radioisotopically labelled serum albumin added to dialysate as a volume marker were analysed in 31 continuous ambulatory PD patients, 20 with normal ultrafiltration (NUF) and 11 with UFF. For each patient, the physiologically based parameters were evaluated for both transport barriers using the spatially distributed approach based on the individual intraperitoneal profiles of volume and concentrations of glucose, sodium, urea and creatinine.

          Results

          UFF patients as compared with NUF patients had increased solute diffusivity in both barriers, peritoneal tissue and capillary wall, decreased tissue hydraulic conductivity and increased local lymphatic absorption and functional decrease in the fraction of the ultra-small pores. This resulted in altered distribution of fluid and solutes in the peritoneal tissue, and decreased penetration depths of fluid and solutes into the tissue in UFF patients.

          Conclusions

          Mathematical modelling using a spatially distributed approach for the description of clinical data suggests that alterations both in the capillary wall and in the tissue barrier contribute to UFF through their effect on transport and distribution of solutes and fluid within the tissue.

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          Most cited references22

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          Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis.

          Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.
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            Peritoneal transport in CAPD patients with permanent loss of ultrafiltration capacity.

            During a 10 year period, 14 out of 227 patients (6.2%) undergoing continuous ambulatory peritoneal dialysis (CAPD) developed permanent loss of ultrafiltration capacity (UFC). The risk of UFC loss increased from 2.6% after one year to 30.9% after six years of treatment. A six hour, single dwell study with glucose 3.86% dialysis fluid was carried out in nine of the UFC loss patients and in 18 CAPD patients with normal UFC. Intraperitoneal dialysate volumes were calculated using 131I-tagged albumin (RISA) as volume marker with a correction applied for its elimination from the peritoneal cavity. The RISA elimination coefficient (KE), which can serve as an estimation of the upper limit of the lymphatic flow, was also calculated. Diffusive mass transport coefficients (KBD) for investigated solutes (glucose, creatinine, urea, potassium, total protein, albumin and beta 2-microglobulin) were calculated during a period of dialysate isovolemia. Two patterns of UFC loss were observed: (a) seven patients had high KBD values for small solutes resulting in rapid uptake of glucose, whereas KBD values for proteins were normal; (b) two patients had normal KBD values but a threefold increase both in the fluid reabsorption rate and KE. We conclude that loss of the osmotic driving force (due to increased diffusive mass transport for small solutes) and increased fluid reabsorption (possibly due to increased lymphatic reabsorption) are the two major causes of permanent loss of UFC in CAPD patients.
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              Intraperitoneal pressure in PD patients: relationship to intraperitoneal volume, body size and PD-related complications.

              The clinical determinants of intraperitoneal pressure (IPP) are ill defined, and the potential impact of elevated IPP on peritoneal dialysis (PD)-related complications is still a matter of debate. We measured IPP in newly started PD patients, assessed its clinical determinants and analysed the incidence of PD-related complications.
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                Author and article information

                Journal
                Nephrology Dialysis Transplantation
                Oxford University Press (OUP)
                0931-0509
                1460-2385
                May 2019
                May 01 2019
                November 06 2018
                May 2019
                May 01 2019
                November 06 2018
                : 34
                : 5
                : 864-870
                Affiliations
                [1 ]Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Warsaw, Poland
                [2 ]National Institutes of Health (NIDDK), Bethesda, MD, USA
                [3 ]Divisions of Baxter Novum and Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
                Article
                10.1093/ndt/gfy313
                6735729
                30403818
                94c56212-10f2-4b17-8475-96cbfcf818e7
                © 2018

                https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model

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