Sodium excretion and the risk of cardiovascular disease in patients with chronic kidney disease

Katherine T. Mills, Jing Chen, Wei Yang, Lawrence J. Appel, John W. Kusek, Arnold Alper, Patrice Delafontaine, Martin G. Keane, Emile Mohler, Akinlolu Ojo, Mahboob Rahman, Ana C. Ricardo, Elsayed Z. Soliman, Susan Steigerwalt, Raymond Townsend, Jiang He

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109 Scopus citations


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: Among3757 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.

Original languageEnglish (US)
Pages (from-to)2200-2210
Number of pages11
JournalJAMA - Journal of the American Medical Association
Issue number20
StatePublished - May 24 2016
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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