Sodium excretion and the risk of cardiovascular disease in patients with chronic kidney disease
Open accessAbstract
IMPORTANCE: Patients with chronic kidney disease (CKD) are at an increased risk of cardiovascular disease (CVD) compared with the general population. Prior studies have produced contradictory results on the association of dietary sodium intake with risk of CVD, and this relationship has not been investigated in patients with CKD. OBJECTIVE: To evaluate the association between urinary sodium excretion and clinical CVD events among patients with CKD. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of patients with CKD from 7 locations in the United States enrolled in the Chronic Renal Insufficiency Cohort Study and followed up from May 2003 to March 2013. EXPOSURES: The cumulative mean of urinary sodium excretion from three 24-hour urinary measurements and calibrated to sex-specific mean 24-hour urinary creatinine excretion. MAIN OUTCOMES AND MEASURES: A composite of CVD events defined as congestive heart failure, stroke, or myocardial infarction. Events were reported every 6 months and confirmed by medical record adjudication. RESULTS: Among 3757 participants (mean age, 58 years; 45% women), 804 composite CVD events (575 heart failure, 305 myocardial infarction, and 148 stroke) occurred during a median 6.8 years of follow-up. From lowest (<2894 mg/24 hours) to highest (≥4548 mg/24 hours) quartile of calibrated sodium excretion, 174, 159, 198, and 273 composite CVD events occurred, and the cumulative incidence was 18.4%, 16.5%, 20.6%, and 29.8% at median follow-up. In addition, the cumulative incidence of CVD events in the highest quartile of calibrated sodium excretion compared with the lowest was 23.2% vs 13.3% for heart failure, 10.9% vs 7.8% for myocardial infarction, and 6.4% vs 2.7% for stroke at median follow-up. Hazard ratios of the highest quartile compared with the lowest quartile were 1.36 (95% CI, 1.09-1.70; P = .007) for composite CVD events, 1.34 (95% CI, 1.03-1.74; P = .03) for heart failure, and 1.81 (95% CI, 1.08-3.02; P = .02) for stroke after multivariable adjustment. Restricted cubic spline analyses of the association between sodium excretion and composite CVD provided no evidence of a nonlinear association (P = .11) and indicated a significant linear association (P < .001). CONCLUSIONS AND RELEVANCE: Among patients with CKD, higher urinary sodium excretion was associated with increased risk of CVD.
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Restriction of dietary sodium to <2,300 mg/day may be useful to manage blood pressure and reduce cardiovascular risk.
“Restriction of dietary sodium (to <2,300 mg/day) may be useful to manage blood pressure and reduce cardiovascular risk (51,52), and individualization of potassium intake may be necessary to manage serum potassium concentrations (27,38,39).”
From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026 (2026) · cites this paper as [51]
The Introduction says the positive association between sodium intake and blood pressure is well established, and the Results associate higher sodium excretion with greater cardiovascular risk in patients with CKD. But the Discussion says the study could not compare outcomes below 2,300 mg/day because too few participants met that target. It therefore does not establish the cardiovascular benefit of restricting intake to that specific level. (LLM, conf=0.90)
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- Authors
- Mills, K. T., Chen, J., Yang, W., Appel, L. J., Kusek, J. W., Alper, A., Delafontaine, P., Keane, M. G., Mohler, E., Ojo, A., Rahman, M., Ricardo, A. C., Soliman, E. Z., Steigerwalt, S., Townsend, R., He, J., & for the Chronic Renal Insufficiency Cohort (CRIC) Study Investigators
- Affiliations
- Tulane University (US)
- University of Pennsylvania (US)
- Johns Hopkins University (US)
- National Institutes of Health (US)
- Temple University (US)
- University of Michigan (US)
- University Hospitals Cleveland Medical Center (US)
- University of Illinois Chicago (US)
- Wake Forest University Health Sciences (US)
- Department of Medicine, St John’s Health System, Detroit, Michigan
- Corresponding author
- He, Jiang
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2016-05-24
- Volume
- 315
- Issue
- 20
- Pages
- 2200
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC5087595
- OpenAlex
- W2403503903
- Cited by
- 232
- References
- 52
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 13 · 2023: 25 · 2022: 22 · 2021: 30 · 2020: 34 · 2019: 23 · 2018: 31 · 2017: 18 · 2016: 12 · 2012: 1
- FWCI
- 29.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5k23dk094829-05, UL1TR000433, UL1TR000424, UL1TR000003, UL1TR000439)
- Clinical and Translational Science Collaborative of Cleveland, School of Medicine, Case Western Reserve University
- National Heart, Lung, and Blood Institute (T32HL007024)
- National Institute of General Medical Sciences (P20GM109036)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK074615, K23-DK-094829, U01DK060990, R01DK139225, U01DK060984, U01DK060902, U01DK060980, U01DK061022, U01DK060963, U01DK061021, U01DK061028)
- National Center for Research Resources (UL1RR024131, M01RR016500, UL1RR029879, M01RR 16500)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Sodium Intake and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Keywords
- chronic kidney disease, sodium excretion, sodium intake, cardiovascular risk, heart failure, myocardial infarction, stroke, 24-hour urine collection, Chronic Renal Insufficiency Cohort Study, cardiovascular events
- MeSH terms
- Adult, Aged, Female, Heart Failure, Humans, Male, Middle Aged, Myocardial Infarction, Prospective Studies, Risk, Sodium, Sodium, Dietary, Stroke, Renal Insufficiency, Chronic, Young Adult
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