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      Increased peritoneal permeability at peritoneal dialysis initiation is a potential cardiovascular risk in patients using biocompatible peritoneal dialysis solution

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          Abstract

          Background

          Cardiovascular disease is a frequent cause of death in peritoneal dialysis patients. Biocompatible peritoneal dialysis solutions with neutral pH have been anticipated to reduce cardiovascular disease more than conventional peritoneal dialysis solutions with low pH, but it remains unclear which factors at peritoneal dialysis initiation increase cardiovascular risk in patients using biocompatible peritoneal dialysis solutions. This study was undertaken to investigate which clinical factors at peritoneal dialysis initiation, including peritoneal transport status, are associated with cardiovascular event in patients using biocompatible peritoneal dialysis solution.

          Methods

          This retrospective cohort study of peritoneal dialysis patients using biocompatible solutions with neutral pH assessed relations of clinical parameters at peritoneal dialysis initiation to cardiovascular event during the subsequent five years.

          Results

          Of 102 patients who started peritoneal dialysis, cardiovascular event occurred in 18. Age, history of cardiovascular disease before peritoneal dialysis initiation, hemoglobin, serum albumin, C-reactive protein, peritoneal permeability defined by the ratio of dialysate to plasma creatinine concentration at 4 hr (D/Pcre) in peritoneal equilibration test (PET), number of patients in each PET category defined by D/Pcre, and peritoneal protein clearance significantly differed between patients with and without cardiovascular event. For patients divided according to PET category using Kaplan–Meier method, the group of high average to high peritoneal transporters exhibited significantly high incidence of cardiovascular event and mortality compared with the groups of low and low-average peritoneal transporters (Log rank; p = 0.0003 and 0.005, respectively). A Cox proportional hazards model showed independent association of PET category classification with cardiovascular event.

          Conclusions

          Peritoneal permeability expressed as PET category at peritoneal dialysis initiation is an independent cardiovascular risk factor in peritoneal dialysis patients using biocompatible peritoneal dialysis solution with neutral pH. Greater peritoneal permeability at peritoneal dialysis initiation might reflect subclinical vascular disorders.

          Electronic supplementary material

          The online version of this article (doi:10.1186/1471-2369-15-173) contains supplementary material, which is available to authorized users.

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          Most cited references18

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          The Euro-Balance Trial: the effect of a new biocompatible peritoneal dialysis fluid (balance) on the peritoneal membrane.

          Although peritoneal dialysis (PD) is a widely accepted form of renal replacement therapy (RRT), concerns remain regarding the bioincompatible nature of standard PD fluid. In order to evaluate whether a newly formulated fluid of neutral pH, and containing low levels of glucose degradation products (GDP), resulted in improved in vivo biocompatibility, it was compared in a clinical study to a standard PD fluid. In a multicenter, open, randomized, prospective study with a crossover design and parallel arms, a conventional, acidic, lactate-buffered fluid (SPDF) was compared with a pH neutral, lactate-buffered, low GDP fluid (balance). Overnight effluent was collected and assayed for cancer antigen 125 (CA125), hyaluronic acid (HA), procollagen peptide (PICP), vascular endothelial growth factor (VEGF), and tumor necrosis factor alpha (TNFalpha). Serum samples were assayed for circulating advanced glycosylation end products (AGE), N(epsilon)-(carboxymethyl)lysine (CML), and imidazolone. Clinical end points were residual renal function (RRF), adequacy of dialysis, ultrafiltration, and peritoneal membrane function. Eighty-six patients were randomized to either group I starting with SPDF for 12 weeks (Phase I), then switching to "balance" for 12 weeks (Phase II), or group II, which was treated vice versa. Seventy-one patients completed the study with data suitable for entry into the per protocol analysis. Effluent and serum samples, together with peritoneal function tests and adequacy measurements, were undertaken at study centers on three occasions during the study: after the four-week run-in period, after Phase I, and again after Phase II. In patients treated with balance there were significantly higher effluent levels of CA125 and PICP in both arms of the study. Conversely, levels of HA were lower in patients exposed to balance, while there was no change in the levels of either VEGF or TNFalpha. Serum CML and imidazolone levels fell significantly in balance-treated patients. Renal urea and creatinine clearances were higher in both treatment arms after patients were exposed to balance. Urine volume was higher in patients exposed to balance. In contrast, peritoneal ultrafiltration was higher in patients on SPDF. When anuric patients were analyzed as a subgroup, there was no significant difference in peritoneal transport characteristics or in ultrafiltration on either fluid. There were no changes in peritonitis incidence on either solution. This study indicates that the use of balance, a neutral pH, low GDP fluid, is accompanied by a significant improvement in effluent markers of peritoneal membrane integrity and significantly decreased circulating AGE levels. Clinical parameters suggest an improvement in residual renal function on balance, with an accompanying decrease in peritoneal ultrafiltration. It would appear that balance solution results in an improvement in local peritoneal homeostasis, as well as having a positive impact on systemic parameters, including circulating AGE and residual renal function.
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            Meta-analysis: peritoneal membrane transport, mortality, and technique failure in peritoneal dialysis.

            Peritoneal membrane solute transport in peritoneal dialysis (PD) patients is assessed by the peritoneal equilibration test, which measures the ratio of creatinine in the dialysate to plasma after a standardized 4-h dwell (D/Pc). Patients then are classified as high, high-average, low-average, or low transporters on the basis of this result. A meta-analysis of observational studies was carried out to characterize the relationship between D/Pc and mortality and technique failure in patients who are on PD. Citations were identified in Medline by using a combination of Medical Subject Heading search terms and key words related to PD, peritoneal membrane permeability/transport, and mortality and technique failure. The table of contents of relevant journals and bibliographies of relevant citations were reviewed in duplicate. Twenty studies that met study criteria were identified. Nineteen studies were pooled to generate a summary mortality relative risk of 1.15 for every 0.1 increase in the D/Pc (95% confidence interval 1.07 to 1.23; P < 001). This result equated to an increased mortality risk of 21.9, 45.7, and 77.3% in low-average, high-average, and high transporters, respectively, as compared with patients with low transport status. Meta-regression analysis showed that the proportion of patients who were on continuous cycler PD within a study was inversely proportional to the mortality risk (P = 0.05). The pooled summary relative risk for death-censored technique failure was 1.18 (95% confidence interval 0.96 to 1.46; P = 0.12) for every 0.1 increase in the D/Pc. This meta-analysis demonstrates that a higher peritoneal membrane solute transport rate is associated with a higher mortality risk and a trend to higher technique failure.
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              Cardiovascular risk in the peritoneal dialysis patient.

              Cardiovascular death is the most frequent cause of death in patients on peritoneal dialysis. Risk factors for cardiovascular death in these patients include those that affect the general population as well as those related to end-stage renal disease (ESRD) and those that are specific to peritoneal dialysis. The development of overhydration after loss of residual renal function is probably the most important cardiovascular risk factor specific to peritoneal dialysis. The high glucose load associated with peritoneal dialysis may lead to insulin resistance and to the development of an atherogenic lipid profile. The presence of glucose degradation products in conventional dialysis solutions, which leads to the local formation of advanced glycation end products, is also specific to peritoneal dialysis. Other risk factors that are not specific to peritoneal dialysis but are related to ESRD include calcifications and protein-energy wasting. When present together with inflammation and atherosclerosis, protein-energy wasting is associated with a marked increase in the risk of cardiovascular death. Obesity is not associated with increased cardiovascular risk in patients on any form of dialysis. Left ventricular hypertrophy and increased arterial stiffness are the most important risk factors for cardiovascular events in the general population.
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                Author and article information

                Contributors
                yhamasaki-tky@umin.ac.jp
                kdoi-tky@umin.ac.jp
                mototsugu.tanaka@gmail.com
                kumeh-uro@h.u-tokyo.ac.jp
                yi431204@aol.com
                yenomoto-tky@umin.ac.jp
                toshiro.fujita@rcast.u-tokyo.ac.jp
                homma-uro@umin.ac.jp
                mnangaku-tky@umin.ac.jp
                noiri-tky@umin.ac.jp
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central (London )
                1471-2369
                1 November 2014
                1 November 2014
                2014
                : 15
                : 1
                : 173
                Affiliations
                [ ]22nd Century Medical and Research Center, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo, Tokyo, Japan
                [ ]Emergency and Critical Care Medicine, The University of Tokyo Hospital, Tokyo, Japan
                [ ]Nephrology and Endocrinology, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, Japan
                [ ]Urology, The University of Tokyo Hospital, Tokyo, Japan
                [ ]Japanese Red Cross Medical Center, Tokyo, Japan
                [ ]Mitsui Memorial Hospital, Tokyo, Japan
                [ ]Division of Clinical Epigenetics, Research Center for Advanced Science and Technology (RCAST), The University of Tokyo, Tokyo, Japan
                Article
                862
                10.1186/1471-2369-15-173
                4230909
                25361694
                80f14163-ef77-485d-939b-62c7d8b7c018
                © Hamasaki et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 17 July 2014
                : 24 October 2014
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2014

                Nephrology
                biocompatible peritoneal dialysis solution,cardiovascular disease,peritoneal dialysis,peritoneal equilibration test,peritoneal permeability

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