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      Dialyzer surface area is a significant predictor of mortality in patients on hemodialysis: a 3-year nationwide cohort study

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          Abstract

          A target Kt/V of > 1.4 and use of a high-flux dialyzer are recommended for patients on hemodialysis. However, there is little information on the relationship between the dialyzer surface area and mortality in these patients. In this nationwide cohort study, we aimed to clarify this relationship by analyzing data from the Japanese Society for Dialysis Therapy for 2010–2013. We enrolled 234,638 patients on hemodialysis who were divided according to quartile for dialyzer surface area into the S group (small, < 1.5 m 2), M group (medium, 1.5 m 2), L group (large, 1.6 to < 2.0 m 2), or XL group (extra-large, ≥ 2.0 m 2). We assessed the association of each group with 3-year mortality using Cox proportional hazards models and performed propensity score matching analysis. By the end of 2013, a total of 53,836 patients on dialysis (22.9%) had died. There was a significant decrease in mortality with larger dialyzer surface areas. The hazard ratio (95% confidence interval) was significantly higher in the S group (1.15 [1.12–1.19], P < 0.0001) and significantly lower in the L group (0.89 [0.87–0.92] P < 0.0001) and XL group (0.75 [0.72–0.78], P < 0.0001) than in the M group as a reference after adjustment for all confounders. Findings were robust in several sensitivity analyses. Furthermore, the findings remained significant after propensity score matching. Hemodialysis using dialyzers, especially super high-flux dialyzers with a larger surface area might reduce mortality rates, and a surface area of ≥ 2.0 m 2 is superior, even with the same Kt/V.

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          KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 update.

          (2015)
          The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) has provided evidence-based guidelines for all stages of chronic kidney disease (CKD) and related complications since 1997. The 2015 update of the KDOQI Clinical Practice Guideline for Hemodialysis Adequacy is intended to assist practitioners caring for patients in preparation for and during hemodialysis. The literature reviewed for this update includes clinical trials and observational studies published between 2000 and March 2014. New topics include high-frequency hemodialysis and risks; prescription flexibility in initiation timing, frequency, duration, and ultrafiltration rate; and more emphasis on volume and blood pressure control. Appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) approach. Limitations of the evidence are discussed and specific suggestions are provided for future research.
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            Review on uremic toxins: classification, concentration, and interindividual variability.

            The choice of the correct concentration of potential uremic toxins for in vitro, ex vivo, and in vivo experiments remains a major area of concern; errors at this level might result in incorrect decisions regarding therpeutic correction of uremia and related clinical complications. An encyclopedic list of uremic retention solutes was composed, containing their mean normal concentration (CN), their highest mean/median uremic concentration (CU), their highest concentration ever reported in uremia (CMAX), and their molecular weight. A literature search of 857 publications on uremic toxicity resulted in the selection of data reported in 55 publications on 90 compounds, published between 1968 and 2002. For all compounds, CU and/or CMAX exceeded CN. Molecular weight was lower than 500 D for 68 compounds; of the remaining 22 middle molecules, 12 exceeded 12,000 D. CU ranged from 32.0 ng/L (methionine-enkephalin) up to 2.3 g/L (urea). CU in the ng/L range was found especially for the middle molecules (10/22; 45.5%), compared with 2/68 (2.9%) for a molecular weight <500 D (P < 0.002). Twenty-five solutes (27.8%) were protein bound. Most of them had a molecular weight <500 D except for leptin and retinol-binding protein. The ratio CU/CN, an index of the concentration range over which toxicity is exerted, exceeded 15 in the case of 20 compounds. The highest values were registered for several guanidines, protein-bound compounds, and middle molecules, to a large extent compounds with known toxicity. A ratio of CMAX/CU <4, pointing to a Gaussian distribution, was found for the majority of the compounds (74/90; 82%). For some compounds, however, this ratio largely exceeded 4 [e.g., for leptin (6.81) or indole-3-acetic acid (10.37)], pointing to other influencing factors than renal function, such as gender, genetic predisposition, proteolytic breakdown, posttranslation modification, general condition, or nutritional status. Concentrations of retention solutes in uremia vary over a broad range, from nanograms per liter to grams per liter. Low concentrations are found especially for the middle molecules. A substantial number of molecules are protein bound and/or middle molecules, and many of these exert toxicity and are characterized by a high range of toxic over normal concentration (CU/CN ratio). Hence, uremic retention is a complex problem that concerns many more solutes than the current markers of urea and creatinine alone. This list provides a basis for systematic analytic approaches to map the relative importance of the enlisted families of toxins.
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              Longer treatment time and slower ultrafiltration in hemodialysis: associations with reduced mortality in the DOPPS.

              Longer treatment time (TT) and slower ultrafiltration rate (UFR) are considered advantageous for hemodialysis (HD) patients. The study included 22,000 HD patients from seven countries in the Dialysis Outcomes and Practice Patterns Study (DOPPS). Logistic regression was used to study predictors of TT > 240 min and UFR > 10 ml/h/kg bodyweight. Cox regression was used for survival analyses. Statistical adjustments were made for patient demographics, comorbidities, dose of dialysis (Kt/V), and body size. Europe and Japan had significantly longer (P 240 min was independently associated with significantly lower relative risk (RR) of mortality (RR = 0.81; P = 0.0005). Every 30 min longer on HD was associated with a 7% lower RR of mortality (RR = 0.93; P 10 ml/h/kg was associated with higher odds of intradialytic hypotension (odds ratio = 1.30; P = 0.045) and a higher risk of mortality (RR = 1.09; P = 0.02). Longer TT and higher Kt/V were independently as well as synergistically associated with lower mortality. Rapid UFR during HD was also associated with higher mortality risk. These results warrant a randomized clinical trial of longer dialysis sessions in thrice-weekly HD.
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                Author and article information

                Contributors
                abe.masanori@nihon-u.ac.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                18 October 2021
                18 October 2021
                2021
                : 11
                : 20616
                Affiliations
                [1 ]GRID grid.458411.d, ISNI 0000 0004 5897 9178, The Committee of Renal Data Registry, , Japanese Society for Dialysis Therapy, ; Tokyo, Japan
                [2 ]GRID grid.260969.2, ISNI 0000 0001 2149 8846, Division of Nephrology, Hypertension and Endocrinology, Department of Internal Medicine, , Nihon University School of Medicine, ; 30-1 Oyaguchi, Kami-cho, Itabashi-ku, Tokyo, 173-8610 Japan
                [3 ]Yabuki Hospital, Yamagata, Japan
                [4 ]Department of Nephrology, Kitasaito Hospital, Asahikawa, Japan
                [5 ]GRID grid.256115.4, ISNI 0000 0004 1761 798X, Department of Clinical Engineering, , Fujita Health University, ; Toyoake, Aichi Japan
                [6 ]GRID grid.410818.4, ISNI 0000 0001 0720 6587, Department of Nephrology, , Tokyo Women’s Medical University, ; Tokyo, Japan
                [7 ]GRID grid.410802.f, ISNI 0000 0001 2216 2631, Department of General Internal Medicine, , Saitama Medical University, ; Saitama, Japan
                Article
                99834
                10.1038/s41598-021-99834-4
                8523692
                fab1db10-a8d6-413d-8b80-9b68d9ffd555
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 1 June 2021
                : 1 October 2021
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                nephrology,renal replacement therapy,haemodialysis
                Uncategorized
                nephrology, renal replacement therapy, haemodialysis

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