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      Regimen-related Mortality Risk in Patients Undergoing Peritoneal Dialysis Using Hypertonic Glucose Solution: A Retrospective Cohort Study

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          Abstract

          Objectives

          The main purpose of this study was to quantify the risk of mortality linked to various regimens of hypertonic peritoneal dialysis (PD) solution.

          Methods

          A retrospective cohort study of patients using home-based PD was carried out. The prescribed regimen of glucose-based PD solution for all patients, determined on the basis of their individual conditions, was extracted from their medical chart records. The primary outcome was death. The treatment regimens were categorized into 3 groups according to the type of PD solution used: original PD (1.5% glucose), shuffle PD (1.5 and 2.5% glucose), and serialized PD (2.5 and 4.5% glucose). Multivariate analysis (using the Weibull model) was applied to comprehensively examine survival probabilities related to the explanatory variable, while adjusting for other potential confounders.

          Results

          Of 300 consecutive patients, 38% died over a median follow-up time of 30 months (interquartile range: 15-46 months). Multivariate analysis showed that a treatment regimen with continued higher-strength PD solution (serialized PD) resulted in a lower survival rate than when the conventional strength solution was used (adjusted hazard ratio, 2.6; 95% confidence interval, 1.6 to 4.6, p<0.01). Five interrelated risk factors (age, length of time on PD, hemoglobin levels, albumin levels, and oliguria) were significant predictors contributing to the outcome.

          Conclusions

          Frequent exposure to high levels of glucose PD solution significantly contributed to a 2-fold higher rate of death, especially when hypertonic glucose was prescribed continuously.

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          Most cited references30

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          Peritoneal glucose exposure and changes in membrane solute transport with time on peritoneal dialysis.

          Peritoneal solute transport increases with time on treatment in a proportion of peritoneal dialysis (PD) patients, contributing to ultrafiltration failure. Continuous exposure of the peritoneum to hypertonic glucose solutions results in morphologic damage that may have a causative role in changes in peritoneal function. The purpose of this analysis was to establish whether increased exposure to glucose preceded changes in solute transport in a selected group of long-term PD patients. Peritoneal solute transport, residual renal function, peritonitis rate, and peritoneal exposure to glucose were recorded prospectively in a cohort of 303 patients at a single dialysis center. A subgroup of individuals, treated continuously for 5 yr, were identified and defined retrospectively as having either stable or increasing transport status. Of the 22 patients who were treated continuously for 5 yr, 13 had stable solute transport (solute transport at start, 0.67 [+/-0.1]; at 5 yr, 0.67 [+/-0.1]), whereas 9 had a sustained increase (solute transport at start, 0.56 [+/-0.08]; at 5 yr, 0.77 [+/-0.09]). Compared with the stable patients, those with increasing transport had earlier loss in residual renal function and were exposed to significantly more hypertonic glucose during the first 2 yr of treatment that preceded the increase in solute transport. This was associated with greater achieved ultrafiltration compensating for the reduced urinary volumes in these patients. Further increases in glucose exposure were observed as solute transport continued to rise. Peritonitis, including severity of infection and causative organism, was similar in both groups. In this selected group of long-term survivors on PD, an increase in solute transport with time was preceded by increased peritoneal exposure to hypertonic glucose. This is supportive evidence that hypertonic glucose may play a causative role in alterations in peritoneal membrane function.
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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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              Relationship between metabolic risk factor clustering and cardiovascular mortality stratified by high blood glucose and obesity: NIPPON DATA90, 1990-2000.

              Metabolic syndrome is diagnosed according to several criteria. Of these, some require glucose intolerance and others require obesity for the diagnosis. We investigated the relationship between metabolic risk factor clustering and cardiovascular disease (CVD) mortality stratified by high blood glucose or obesity. We followed 7,219 Japanese men and women without a history of CVD for 9.6 years. We defined high blood pressure, high blood glucose, high triglycerides, low HDL cholesterol, and obesity as metabolic factors. The multivariate adjusted hazard ratio (HR) for CVD mortality according to the number of clustering metabolic factors was calculated using the Cox proportional hazards model. During follow-up, 173 participants died of CVD. The numbers of metabolic risk factors and CVD mortality were positively correlated (P(trend) = 0.07). The HR was obviously higher among participants with than among those without high blood glucose and clustering of > or =2 other metabolic risk factors (HR 3.67 [95% CI 1.49-9.03]). However, the risk increase was only modest in participants without high blood glucose even if they had > or =2 other metabolic risk factors (1.99 [0.93-4.28]). Conversely, metabolic risk factor clustering was related to CVD mortality irrespective of obesity. Our findings suggest that glucose tolerance plays an important role in CVD mortality. Because the prevalence of nonobese participants with several metabolic risk factors was quite high and their CVD risk was high, excluding them from the diagnosis of metabolic syndrome because of the absence of obesity might overlook their risk.
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                Author and article information

                Journal
                J Prev Med Public Health
                J Prev Med Public Health
                JPMPH
                Journal of Preventive Medicine and Public Health
                Korean Society for Preventive Medicine
                1975-8375
                2233-4521
                July 2018
                19 June 2018
                : 51
                : 4
                : 205-212
                Affiliations
                [1 ]Doctor of Public Health Program, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand
                [2 ]Division of Nephrology, Department of Medicine, Khon Kaen University, Khon Kaen, Thailand
                [3 ]Department of Epidemiology and Biostatistics, Faculty of Public Health, Khon Kaen University, Khon Kaen, Thailand
                Author notes
                Corresponding author: Supannee Promthet, PhD Department of Epidemiology and Biostatistics, Faculty of Public Health, Khon Kaen University, Khon Kaen 40002, Thailand E-mail: supannee@ 123456kku.ac.th
                Author information
                http://orcid.org/0000-0002-6935-2691
                http://orcid.org/0000-0001-5787-1948
                Article
                jpmph-51-4-205
                10.3961/jpmph.18.066
                6078912
                30071708
                e2fc4829-2f55-4cbd-8060-8becd6c3fbd4
                Copyright © 2018 The Korean Society for Preventive Medicine

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 March 2018
                : 11 June 2018
                Categories
                Original Article

                Public health
                death,glucose,kidney diseases,peritoneal dialysis,survival rate,thailand
                Public health
                death, glucose, kidney diseases, peritoneal dialysis, survival rate, thailand

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