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      Pre-dialysis Hyponatremia and Change in Serum Sodium Concentration During a Dialysis Session Are Significant Predictors of Mortality in Patients Undergoing Hemodialysis

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          Abstract

          Background

          Previous studies have shown that hyponatremia is associated with greater mortality in hemodialysis (HD) patients. However, there have been few reports regarding the importance of the change in serum sodium (SNa) concentration (ΔSNa) during dialysis sessions. To investigate the relationships of pre-dialysis hyponatremia and ΔSNa during a dialysis session with mortality, we analyzed data from a national registry of Japanese patients with end-stage kidney disease.

          Methods

          We identified 178,114 patients in the database who were undergoing HD 3 times weekly. The study outcome was 2-year all-cause mortality, and the baseline SNa concentrations were categorized into quintiles. We evaluated the relationships of SNa concentration and ΔSNa with mortality using Cox proportional hazards models.

          Results

          During a 2-year follow-up period, 25,928 patients died. Each 1-mEq/l reduction in pre-HD SNa concentration was associated with a cumulatively greater risk of all-cause mortality (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.05–1.06). In contrast, a larger ΔSNa was associated with higher all-cause mortality (HR for a 1-mEq/l increase in ΔSNa, 1.02; 95% CI 1.01–1.02). The combination of low pre-HD SNa concentration and large ΔSNa was also associated with higher mortality (HR 1.09; 95% CI 1.05–1.13). Participants with the lowest SNa concentration (≤136 mEq/L) and the highest ΔSNa (>4 mEq/L) showed higher mortality than those with an intermediate pre-HD SNa concentration (137–140 mEq/L) and the lowest ΔSNa (≤2 mEq/L).

          Conclusions

          Lower pre-HD SNa concentration and higher ΔSNa are associated with a greater risk of mortality in patients undergoing HD.

          Graphical abstract

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          Most cited references 26

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          Relationship between admission serum sodium concentration and clinical outcomes in patients hospitalized for heart failure: an analysis from the OPTIMIZE-HF registry.

          Hyponatraemia has been shown to be an independent predictor of mortality in selected patients with heart failure enrolled in clinical trials. The predictive value of hyponatraemia has not been evaluated in unselected patients hospitalized with heart failure. OPTIMIZE-HF is a registry and performance-improvement programme for patients hospitalized with heart failure and includes a subgroup with 60-90 day follow-up data. The relationship between admission serum sodium concentration and clinical outcomes was analysed in 48,612 patients from 259 hospitals. Admission serum sodium levels were analysed both as a continuous variable and by grouping patients with admission Na or = 135 mmol/L. Patients with hyponatraemia (Na or =135 mmol/L. Patients with hyponatraemia were more likely to be Caucasian, have lower admission systolic blood pressure, and receive intravenous inotropes during hospitalization. Patients with hyponatraemia had significantly higher rates of in-hospital and follow-up mortality and longer hospital stays, although no difference in re-admission rates was observed. After adjusting for differences with multivariable analysis, the risk of in-hospital death increased by 19.5%, the risk of follow-up mortality by 10%, and the risk of death or rehospitalization by 8% for each 3 mmol/L decrease in admission serum sodium below 140 mmol/L. Hyponatraemia in hospitalized patients with heart failure is relatively common and is associated with longer hospital stays and higher in-hospital and early post-discharge mortality. Re-admission rates were equally high in patients with or without hyponatraemia.
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            Hyponatremia and mortality: moving beyond associations.

            Acute hyponatremia can cause death if cerebral edema is not treated promptly. Conversely, if chronic hyponatremia is corrected too rapidly, osmotic demyelination may ensue, which also potentially is lethal. However, these severe complications of hyponatremia are relatively uncommon and often preventable. More commonly, hyponatremia predicts mortality in patients with advanced heart failure or liver cirrhosis. In these conditions, it generally is assumed that hyponatremia reflects the severity of the underlying disease rather than contributing directly to mortality. The same assumption holds for the recently reported associations between hyponatremia and mortality in patients with pulmonary embolism, pulmonary hypertension, pneumonia, and myocardial infarction. However, recent data suggest that chronic and mild hyponatremia in the general population also are associated with mortality. In addition, hyponatremia has been associated with mortality in long-term hemodialysis patients without residual function in whom the underlying disease cannot be responsible for hyponatremia. These new data raise the question of whether hyponatremia by itself can contribute to mortality or it remains a surrogate marker for other unknown risk factors. We review hyponatremia and mortality and explore the possibility that hyponatremia perturbs normal physiology in the absence of cerebral edema or osmotic demyelination. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
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              Overview of regular dialysis treatment in Japan (as of 31 December 2008).

              A nationwide statistical survey of 4124 dialysis facilities was conducted at the end of 2008 and 4081 facilities (99.0%) responded. The number of patients undergoing dialysis at the end of 2008 was determined to be 283,421, an increase of 8179 patients (3.0%) compared with that at the end of 2007. The number of dialysis patients per million at the end of 2008 was 2220. The crude death rate of dialysis patients from the end of 2007 to the end of 2008 was 9.8%. The mean age of the new patients begun on dialysis was 67.2 years and the mean age of the entire dialysis patient population was 65.3 years. For the primary diseases of the new patients begun on dialysis, the percentages of patients with diabetic nephropathy and chronic glomerulonephritis were 43.3% and 22.8%, respectively. Among the facilities that measured bacterial count in the dialysate solution in 2008, 52.0% of facilities ensured that a minimum dialysate solution volume of 10 mL was sampled. Among the patients treated by facility dialysis, 95.4% of patients were treated three times a week, and the average time required for one treatment was 3.92 ± 0.53 (SD) h. The average amounts of blood flow and dialysate solution flow were 197 ± 31 and 487 ± 33 mL/min, respectively. The number of patients using a polysulfone membrane dialyzer was the largest (50.7%) and the average membrane area was 1.63 ± 0.35 m(2). According to the classification of dialyzers by function, the number of patients using a type IV dialyzer was the largest (80.3%). The average concentrations of each electrolyte before treatment in patients treated with blood purification by extracorporeal circulation were 138.8 ± 3.3 mEq/L for serum sodium, 4.96 ± 0.81 mEq/L for serum potassium, 102.1 ± 3.1 mEq/L for serum chloride, and 20.7 ± 3.0 mEq/L for HCO(3) (-) ; the average serum pH was 7.35 ± 0.05. Regarding the type of vascular access in patients treated by facility dialysis, in 89.7% of patients an arteriovenous fistula was used and in 7.1% an arteriovenous graft was used. The percentage of hepatitis C virus (HCV)-positive patients who were HCV-negative in 2007 was 1.04%; the percentage is particularly high in patients with a period of dialysis of 20 years or longer. The risk of becoming HCV-positive was high in patients with low serum creatinine, serum albumin, and serum total cholesterol levels, and/or a low body mass index before beginning dialysis. © 2010 The Authors. Journal compilation © 2010 International Society for Apheresis.
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                Author and article information

                Contributors
                Journal
                Kidney Int Rep
                Kidney Int Rep
                Kidney International Reports
                Elsevier
                2468-0249
                29 December 2020
                February 2021
                29 December 2020
                : 6
                : 2
                : 342-350
                Affiliations
                [1 ]Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
                [2 ]Division of Nephrology, Toho University Ohashi Medical Center, Meguro, Tokyo, Japan
                [3 ]Department of Medical Science, Kawasaki Medical School, Kurashiki, Okayama, Japan
                [4 ]Department of Nephrology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
                [5 ]Department of Nephrology, Yabuki Hospital, Yamagata, Japan
                [6 ]Department of Nephrology, Nara Medical University, Kashihara, Nara, Japan
                Author notes
                [] Correspondence: Kiichiro Fujisaki, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 819–0395 Japan. kiichiro.fujisaki@ 123456nifty.ne.jp
                Article
                S2468-0249(20)31720-4
                10.1016/j.ekir.2020.11.009
                7879213
                © 2020 International Society of Nephrology. Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                Categories
                Clinical Research

                prospective cohort, hemodialysis, mortality, hyponatremia

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