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      Precedent Fluctuation of Serum hs-CRP to Albumin Ratios and Mortality Risk of Clinically Stable Hemodialysis Patients

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          Abstract

          Background

          A high sensitivity C-reactive protein to albumin ratio (hs-CRP/Alb) predicts mortality risk in patients with acute kidney injury. However, it varies dynamically. This study was conducted to evaluate whether a variation of this marker was associated with long-term outcome in clinically stable hemodialysis (HD) patients.

          Methods

          hs-CRP/Alb was checked bimonthly in 284 clinically stable HD outpatients throughout all of 2008. Based on the “slope” of trend equation derived from 5–6 hs-CRP/alb ratios for each patient, the total number of patients was divided into quartiles—Group 1: β≦ −0.13, n = 71; group 2: β>-0.13≦0.003; n = 71, group 3: β>0.003≦0.20; and group 4: β>0.20, n = 71. The observation period was from January 1, 2009 to August 31, 2012.

          Results

          Group 1+4 showed a worse long-term survival (p = 0.04) and a longer 5-year hospitalization stay than Group 2+3 (38.7±44.4 vs. 16.7±22.4 days, p<0.001). Group 1+4 were associated with older age (OR = 1.03, 95% CI = 1.01–1.05) and a high prevalence of congestive heart failure (OR = 2.02, 95% CI = 1.00–4.11). Standard deviation (SD) of hs-CRP/Alb was associated with male sex (β = 0.17, p = 0.003), higher Davies co-morbidity score (β = 0.16, p = 0.03), and baseline hs-CRP (β = 0.39, p<0.001). Patients with lower baseline and stable trend of hs-CRP/Alb had a better prognosis. By multivariate Cox proportional methods, SD of hs-CRP/alb (HR: 1.05, 95% CI: 1.01–1.08) rather than baseline hs-CRP/Alb was an independent predictive factor for long-term mortality after adjusting for sex and HD vintage.

          Conclusion

          Clinically stable HD patients with a fluctuating variation of hs-CRP/Alb are characterized by old age, and more co-morbidity, and they tend to have longer subsequent hospitalization stay and higher mortality risk.

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          Most cited references11

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          Serum albumin: relationship to inflammation and nutrition.

          Hypoalbuminemia is the result of the combined effects of inflammation and inadequate protein and caloric intake in patients with chronic disease such as chronic renal failure. Inflammation and malnutrition both reduce albumin concentration by decreasing its rate of synthesis, while inflammation alone is associated with a greater fractional catabolic rate (FCR) and, when extreme, increased transfer of albumin out of the vascular compartment. A vicious cascade of events ensues in which inflammation induces anorexia and reduces the effective use of dietary protein and energy intake and augments catabolism of the key somatic protein, albumin. Hypoalbuminemia is a powerful predictor of mortality in patients with chronic renal failure, and the major cause of death in this population is due to cardiovascular events. Inflammation is associated with vascular disease and likely causes injury to the vascular endothelium, and hypoalbuminemia as two separate expressions of the inflammatory process. Albumin has a myriad of important physiologic effects that are essential for normal health. However, simply administering albumin to critically ill patients with hypoalbuminemia has not been shown to improve survival or reduce morbidity. Thus the inference from these clinical studies suggests that the cause of hypoalbuminemia, rather than low albumin levels specifically, is responsible for morbidity and mortality.
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            Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences.

            Protein-energy malnutrition (PEM) and inflammation are common and usually concurrent in maintenance dialysis patients. Many factors that appear to lead to these 2 conditions overlap, as do assessment tools and such criteria for detecting them as hypoalbuminemia. Both these conditions are related to poor dialysis outcome. Low appetite and a hypercatabolic state are among common features. PEM in dialysis patients has been suggested to be secondary to inflammation; however, the evidence is not conclusive, and an equicausal status or even opposite causal direction is possible. Hence, malnutrition-inflammation complex syndrome (MICS) is an appropriate term. Possible causes of MICS include comorbid illnesses, oxidative and carbonyl stress, nutrient loss through dialysis, anorexia and low nutrient intake, uremic toxins, decreased clearance of inflammatory cytokines, volume overload, and dialysis-related factors. MICS is believed to be the main cause of erythropoietin hyporesponsiveness, high rate of cardiovascular atherosclerotic disease, decreased quality of life, and increased mortality and hospitalization in dialysis patients. Because MICS leads to a low body mass index, hypocholesterolemia, hypocreatininemia, and hypohomocysteinemia, a "reverse epidemiology" of cardiovascular risks can occur in dialysis patients. Therefore, obesity, hypercholesterolemia, and increased blood levels of creatinine and homocysteine appear to be protective and paradoxically associated with a better outcome. There is no consensus about how to determine the degree of severity of MICS or how to manage it. Several diagnostic tools and treatment modalities are discussed. Successful management of MICS may ameliorate the cardiovascular epidemic and poor outcome in dialysis patients. Clinical trials focusing on MICS and its possible causes and consequences are urgently required to improve poor clinical outcome in dialysis patients.
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              Plasma interleukin-6 is independently associated with mortality in both hemodialysis and pre-dialysis patients with chronic kidney disease.

              Chronic inflammation associated with chronic kidney disease predicts all-cause and cardiovascular mortality in hemodialysis patients. Here we sought to evaluate the association between plasma levels of the inflammatory mediator interleukin-6 (IL-6) and mortality and aortic calcification/stiffness in 125 patients at different stages (2-5D) of chronic kidney disease. Using multivariate linear regression, we found that plasma IL-6 was independently associated with C-reactive protein, albumin and the stage of chronic kidney disease, but not the aortic calcification score or pulse wave velocity. During follow-up studies (median of 829 days), 38 patients died, 22 from cardiovascular events. Plasma IL-6 significantly predicted overall and cardiovascular mortality; this association persisted after multiple adjustments or restricting the analysis to pre-dialysis patients. Moreover, IL-6 was a significantly better predictor of mortality than C-reactive protein, albumin or tumor necrosis factor-alpha. Hence, plasma IL-6 independently predicted overall and cardiovascular mortality in patients at different stages of chronic kidney disease; however, whether lowering plasma IL-6 will affect the outcome of chronic kidney disease will require more direct evaluation.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 March 2015
                2015
                : 10
                : 3
                : e0120266
                Affiliations
                [1 ]Division of Nephrology, Chi Mei Medical Center, Tainan, Taiwan
                [2 ]Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy and Science, Tainan, Taiwan
                Sao Paulo State University, BRAZIL
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JCH. Performed the experiments: MYJ YHL. Analyzed the data: CTW. Contributed reagents/materials/analysis tools: JCH CTW. Wrote the paper: JCH.

                Article
                PONE-D-14-42758
                10.1371/journal.pone.0120266
                4368637
                25793462
                5ac3886d-9975-45b3-956c-9c4dc65e4134
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 30 September 2014
                : 21 January 2015
                Page count
                Figures: 4, Tables: 4, Pages: 14
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper.

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