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      Lower serum potassium associated with increased mortality in dialysis patients: A nationwide prospective observational cohort study in Korea

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          Abstract

          Background

          Abnormal serum potassium concentration has been suggested as a risk factor for mortality in patients undergoing dialysis patients. We investigated the impact of serum potassium levels on survival according to dialysis modality.

          Methods

          A nationwide, prospective, observational cohort study for end stage renal disease patients has been ongoing in Korea since August 2008. Our analysis included patients whose records contained data regarding serum potassium levels. The relationship between serum potassium and mortality was analyzed using competing risk regression.

          Results

          A total of 3,230 patients undergoing hemodialysis (HD, 64.3%) or peritoneal dialysis (PD, 35.7%) were included. The serum potassium level was significantly lower ( P < 0.001) in PD (median, 4.5 mmol/L; interquartile range, 4.0–4.9 mmol/L) than in HD patients (median, 4.9 mmol/L; interquartile range, 4.5–5.4 mmol/L). During 4.4 ± 1.7 years of follow-up, 751 patients (23.3%) died, mainly from cardiovascular events (n = 179) and infection (n = 120). In overall, lower serum potassium level less than 4.5 mmol/L was an independent risk factor for mortality after adjusting for age, comorbidities, and nutritional status (sub-distribution hazard ratio, 1.30; 95% confidence interval 1.10–1.53; P = 0.002). HD patients showed a U-shaped survival pattern, suggesting that both lower and higher potassium levels were deleterious, although insignificant. However, in PD patients, only lower serum potassium level (<4.5 mmol/L) was an independent predictor of mortality (sub-distribution hazard ratio, 1.35; 95% confidence interval 1.00–1.80; P = 0.048).

          Conclusion

          Lower serum potassium levels (<4.5 mmol/L) occur more commonly in PD than in HD patients. It represents an independent predictor of survival in overall dialysis, especially in PD patients. Therefore, management of dialysis patients should focus especially on reducing the risk of hypokalemia, not only that of hyperkalemia.

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          Most cited references 44

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          Intersalt: an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion. Intersalt Cooperative Research Group.

          The relations between 24 hour urinary electrolyte excretion and blood pressure were studied in 10,079 men and women aged 20-59 sampled from 52 centres around the world based on a highly standardised protocol with central training of observers, a central laboratory, and extensive quality control. Relations between electrolyte excretion and blood pressure were studied in individual subjects within each centre and the results of these regression analyses pooled for all 52 centres. Relations between population median electrolyte values and population blood pressure values were also analysed across the 52 centres. Sodium excretion ranged from 0.2 mmol/24 h (Yanomamo Indians, Brazil) to 242 mmol/24 h (north China). In individual subjects (within centres) it was significantly related to blood pressure. Four centres found very low sodium excretion, low blood pressure, and little or no upward slope of blood pressure with age. Across the other 48 centres sodium was significantly related to the slope of blood pressure with age but not to median blood pressure or prevalence of high blood pressure. Potassium excretion was negatively correlated with blood pressure in individual subjects after adjustment for confounding variables. Across centres there was no consistent association. The relation of sodium to potassium ratio to blood pressure followed a pattern similar to that of sodium. Body mass index and heavy alcohol intake had strong, significant independent relations with blood pressure in individual subjects.
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            Nonadherence in hemodialysis: associations with mortality, hospitalization, and practice patterns in the DOPPS.

            Nonadherence among hemodialysis patients compromises dialysis delivery, which could influence patient morbidity and mortality. The Dialysis Outcomes and Practice Patterns Study (DOPPS) provides a unique opportunity to review this problem and its determinants on a global level. Nonadherence was studied using data from the DOPPS, an international, observational, prospective hemodialysis study. Patients were considered nonadherent if they skipped one or more sessions per month, shortened one or more sessions by more than 10 minutes per month, had a serum potassium level openface>6.0 mEq/L, a serum phosphate level openface>7.5 mg/dL (>2.4 mmol/L), or interdialytic weight gain (IDWG)>5.7% of body weight. Predictors of nonadherence were identified using logistic regression. Survival analysis used the Cox proportional hazards model adjusting for case-mix. Skipping treatment was associated with increased mortality [relative risk (RR) = 1.30, P = 0.01], as were excessive IDWG (RR = 1.12, P = 0.047) and high phosphate levels (RR = 1.17, P = 0.001). Skipping also was associated with increased hospitalization (RR = 1.13, P = 0.04), as were high phosphate levels (RR = 1.07, P = 0.05). Larger facility size (per 10 patients) was associated with higher odds ratios (OR) of skipping (OR = 1.03, P = 0.06), shortening (OR = 1.03, P = 0.05), and IDWG (OR = 1.02, P = 0.07). An increased percentage of highly trained staff hours was associated with lower OR of skipping (OR = 0.84 per 10%, P = 0.02); presence of a dietitian was associated with lower OR of excessive IDWG (OR = 0.75, P = 0.08). Nonadherence was associated with increased mortality risk (skipping treatment, excessive IDWG, and high phosphate) and with hospitalization risk (skipping, high phosphate). Certain patient/facility characteristics also were associated with nonadherence.
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              Serum and dialysate potassium concentrations and survival in hemodialysis patients.

              Controlling serum potassium is an important goal in maintenance hemodialysis patients. We examined the achievement of potassium balance through hemodialysis treatments and the associated fluctuations in serum potassium. A 3-yr (July 2001 to June 2004) cohort of 81,013 maintenance hemodialysis patients from all DaVita dialysis clinics across the United States were studied. Nine quarterly-averaged serum potassium groups ( or = 6.3 mEq/L and seven increments in-between) and four dialysate potassium concentration groups were created in each of the 12 calendar quarters. The death risk associated with predialysis potassium level and dialysate potassium concentration was examined using unadjusted, case-mix adjusted, and malnutrition-inflammation-adjusted time-dependent survival models. Serum potassium correlated with nutritional markers. Serum potassium between 4.6 and 5.3 mEq/L was associated with the greatest survival, whereas potassium or = 5.6 mEq/L was associated with increased mortality. The death risk of serum potassium > or = 5.6 mEq/L remained consistent after adjustments. Higher dialysate potassium concentration was associated with increased mortality in hyperkalemic patients with predialysis serum potassium > or = 5.0 mEq/L. A predialysis serum potassium of 4.6 to 5.3 mEq/L is associated with the greatest survival in maintenance hemodialysis patients. Hyperkalemic patients who undergo maintenance hemodialysis against lower dialysate bath may have better survival. Limitations of observational studies including confounding by indication should be considered when interpreting these results.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                6 March 2017
                2017
                : 12
                : 3
                Affiliations
                [1 ]Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
                [2 ]Department of Internal Medicine, Dongguk University Gyeongju Hospital, Gyeongju, Republic of Korea
                [3 ]Seoul National University Hospital, Medical Research Collaborating Center, Seoul, Republic of Korea
                [4 ]Seoul National University Kidney Research Institute, Seoul, Republic of Korea
                [5 ]Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Republic of Korea
                [6 ]Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
                [7 ]Department of Internal Medicine, Seoul St. Mary's Hospital, Seoul, Republic of Korea
                [8 ]Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea
                The University of Tokyo, JAPAN
                Author notes

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

                • Conceptualization: SL HL.

                • Data curation: DKK KWJ.

                • Formal analysis: YC EK KDY.

                • Funding acquisition: YSK YLK SWK CWY NHK.

                • Investigation: YSK YLK SWK CWY NHK.

                • Methodology: EK KDY.

                • Project administration: YSK.

                • Software: SL EK KDY.

                • Supervision: YSK.

                • Visualization: SL SHY.

                • Writing – original draft: SL HL.

                • Writing – review & editing: DKK KWJ.

                Article
                PONE-D-16-32274
                10.1371/journal.pone.0171842
                5338775
                28264031
                © 2017 Lee et al

                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.

                Page count
                Figures: 5, Tables: 3, Pages: 15
                Product
                Funding
                Funded by: Ministry of Health and Welfare of the Republic of Korea
                Award ID: HI10C2020
                This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HC15C1129).
                Categories
                Research Article
                Medicine and Health Sciences
                Nephrology
                Medical Dialysis
                People and Places
                Demography
                Death Rates
                Medicine and Health Sciences
                Nephrology
                Chronic Kidney Disease
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Biology and Life Sciences
                Nutrition
                Malnutrition
                Medicine and Health Sciences
                Nutrition
                Malnutrition
                Research and Analysis Methods
                Research Design
                Cohort Studies
                Medicine and Health Sciences
                Cardiovascular Medicine
                Cardiovascular Diseases
                Physical Sciences
                Chemistry
                Chemical Compounds
                Acids
                Uric Acid
                Custom metadata
                All relevant data are within the paper and its Supporting Information files. Additional data are available from the Clinical Research Center for End Stage Renal Disease (CRC-ESRD) database (URL: http://www.crc-esrd.or.kr/) for only qualified researchers who meet the criteria for access to confidential data.

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